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II. General Treatment Principles
Although many of the principles presented in this section
apply to all substances reviewed in this guideline (i.e., nicotine,
alcohol, marijuana, cocaine, and opioids), not all principles are
applicable to the treatment of every substance use disorder. This
is particularly true for nicotine dependence treatment, as nicotine
dependence rarely causes the behavioral or social harm seen with
other substance dependencies.
Individuals with substance use disorders are heterogeneous
with regard to a number of clinically important features:
- The number and type of substances
used
- The individual's genetic vulnerability for
developing a substance use disorder(s)
- The severity of the disorder, the rapidity with which
it develops, and the degree of associated functional impairment(s)
- The individual's awareness of the substance
use disorder as a problem
- The individual's readiness for change and motivation
to enter into treatment for the purpose of change
- The associated general medical and psychiatric conditions
(either co-occurring or induced by substance use)
- The individual's strengths (protective and
resiliency factors) and vulnerabilities
- The social, environmental, and cultural context in which
the individual lives and will be treated
It is clinically helpful when assessing patients to use a
spectrum that includes use, misuse, abuse, and dependence. The
latter two terms represent formal diagnostic categories. Use of
a substance may or may not be clinically significant. If use of
a substance is thought to be potentially clinically significant
but does not meet diagnostic criteria for abuse or dependence, it
may be characterized as "misuse," although this
is not a formal diagnostic category. Even when functional impairment
is absent or limited, substance misuse can be an early indicator
of an individual's vulnerability to developing a chronic
substance use disorder. Brief early interventions can effectively
reduce this progression (1–3), although follow-up reinforcement
appears necessary for sustained utility. Most individuals presenting
or referred for treatment of a substance use disorder, however,
have been unable to stop using substances on their own. They often
exhibit functional impairments across many categories (e.g., health,
social and family, occupational, financial, legal) and have a history
of chronic or relapsing episodes of problematic substance use. This
practice guideline refers primarily to the care of such individuals.
As with treatment models for chronic diseases, treatment for
individuals with substance use disorders occurs in temporal phases
that include initial assessment, acute intervention, and long-term
intervention and/or maintenance, with frequent reassessment
during episodic flares in substance use (4). During the assessment
phase, the specific variables associated with an individual's
substance use are evaluated (e.g., genetic vulnerability, environmental influences,
behavioral patterns of use, positive and negative consequences of
use, associated conditions that trigger or otherwise interact with
use, risk of withdrawal). In addition, the level of risk for morbidity
or mortality associated with substance use is determined. Immediate
intervention to provide safety to the patient in a medically monitored
environment is recommended for individuals who present with high-risk
intoxication or withdrawal states or altered mental states (e.g.,
psychosis, suicidality, agitation) that are associated with a risk
of danger to self or others. After the patient is stabilized, the
patient's immediate needs regarding safety and stability
should be addressed to prepare the patient to enter into comprehensive,
long-term treatment of the substance use disorder and its associated
conditions. Such acute interventions may be focused on goals such
as preserving health, achieving financial security, and finding
stable housing. It is recommended that individuals in the patient's
family or social network be included in the treatment process so
they may learn about the disorder, help monitor the patient's
progress, and assist in the patient's maintaining existing
relationships or repairing troubled ones (5).
Depending on the clinical circumstances and an individual's
readiness for change (6), treatment strategies may emphasize providing
motivational enhancement, teaching risk-reduction behaviors and
skills, helping the patient achieve abstinence and learn relapse
prevention skills, or combining substitution agonist therapies (e.g.,
methadone or buprenorphine for opioid-dependent individuals, NRTs
for tobacco-dependent individuals) with therapy to help the patient
acquire relapse prevention skills. In addition, individuals with
substance use disorders often require multimodal treatment to address
associated conditions that have contributed to or resulted from
the substance use disorder. Specific pharmacological and psychosocial
treatments for patients with a substance use disorder are reviewed
separately in this guideline; however, in practice they are often
implemented together, as combined treatments lead to better treatment
retention and outcomes (7).
The evidence to date suggests that substance-dependent individuals
who achieve sustained abstinence from the abused substance have
the best long-term outcomes (8, 9). Psychiatrists will, however,
frequently encounter individuals who wish to reduce their substance
use to a "controlled" level (i.e., use without
apparent functional consequences). Although some of these individuals,
particularly those with less severe problems, may be helped to reach
a stable level of use (e.g., "controlled" drinking)
that does not cause morbidity (10), a goal of "controlled" substance
use is unrealistic for most individuals presenting with a substance
use disorder. Furthermore, setting "controlled" use
as a primary goal of treatment may initially dissuade individuals
from working toward abstinence. However, treatment may be initially
facilitated by the clinician's accepting the patient's
goal for moderation while sharing with the patient any reservations
the clinician may have about the likelihood of success. If the clinician
believes that any level of substance use for the individual carries
a risk of acute or chronic negative consequences, he or she should
share with the patient this concern and the belief that long-term
abstinence would be the best course of action. In certain circumstances
it may be reasonable, however, for an individual to begin treatment
by setting a short-term goal of reducing or containing dangerous
substance use as a first step toward achieving the longer-term goal
of sustained abstinence (11).
The goals for treating a substance use disorder begin with
engaging the patient in treatment and may ultimately progress to
the patient's achieving and maintaining complete abstinence
from all problematic substances. Along this treatment spectrum or
timeline, an individual and his or her physician may develop immediate
goals involving risk reduction, such as reducing the frequency and
quantity of substances taken, abstaining from some (but not all)
substances according to assessment of risk (e.g., abstaining from
injected heroin without abstaining from cannabis use), or limiting
substance use to lower-risk situations (e.g., continuing to drink
at home but avoiding drinking in other environments or driving while
drinking). The guiding elements of treatment planning consist of
ongoing efforts to reduce the patient's substance use and
prevent a return to previously dangerous patterns of use. It is
essential to complement this approach with parallel setting of goals
to repair an individual's functional decline and develop
new pathways for safe, sober pleasures. These issues are outlined
below.
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1. Treatment retention and substance use reduction
or abstinence as initial goals of treatment
The ideal outcome for most individuals with substance use
disorders is total cessation of substance use. Nonetheless, many
individuals are either unable or unmotivated to reach this goal,
particularly in the early phases of treatment and/or after
a relapse to substance use. Such individuals can still be helped
to minimize the direct and indirect negative effects of ongoing
substance use. The interventions discussed in this practice guideline
may result in substantial reductions in the general medical, psychiatric,
interpersonal, familial/parental, occupational, or other
difficulties commonly associated with substance abuse or dependence.
For example, reductions in the amount or frequency of substance
use, substitution of a less risky substance, and reduction of high-risk
behaviors associated with substance use may be achievable goals
when abstinence is initially unobtainable (12, 13). Engaging an individual
to participate and remain in treatment that may eventually lead
to further reductions in substance use and its associated morbidity
is a critical early goal of treatment planning and is often enhanced
by motivational interviewing techniques (14).
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2. Reduction in the frequency and severity of substance
use episodes
Reduction in the frequency and severity of substance use episodes
is a primary goal of long-term treatment (15). The individual is
educated about common types of substance use triggers, such as environmental
cues, stress, and exposure to a priming substance (16, 17). The
individual is then helped to develop skills to prevent substance
use; these skills include identifying and avoiding high-risk situations
as well as developing alternative responses to situations in which
substance use may occur. Individuals are at a greater risk of using
substances when any of the following are present: 1) craving or
urges to use a substance due to acute or protracted withdrawal states
and/or classically conditioned responses to cues associated
with substance use (18–20); 2) easy access to substances;
3) social facilitation of substance use (e.g., holiday parties,
association with other substance users); 4) negative affective states;
5) negative life events, or any significant, even positively viewed,
life event if the event carries with it a significant increase in
responsibility (e.g., marriage, the birth of a child, beginning
school or a new job, work promotion); 6) physical discomfort; 7)
unstructured time or boredom; or 8) nonadherence to prescribed treatment.
Many clinicians do not recognize that individuals with substance
use disorders have a chronic condition and may have future episodes
of substance use. Therefore, the clinician may become discouraged
when an individual doing well in treatment over an extended period
of time resumes substance use. A useful clinical strategy is to
explicitly anticipate the reality of future substance use and plan
a strategy for recovery in the event of substance use relapse; such
a strategy helps both the patient and the clinician optimally manage
and contain the negative consequences resulting from a return to
substance use.
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3. Improvement in psychological, social, and adaptive
functioning
Substance use disorders are associated with impairments in
psychological development and social adjustment, family and social
relations, school and work performance, financial status, health,
and personal independence (e.g., as a result of legal charges associated
with substance use, suspension of the individual's driver's
license after being convicted of driving under the influence of
an intoxicating substance) (21). For optimal outcome, the treatment
of a substance use disorder may also include strategies that target
repair of damages or losses that resulted from the individual's
substance use; aid in developing effective interpersonal, vocational,
and proactive coping skills; and enhance familial and interpersonal relations
that will support an abstinent lifestyle. It is particularly important
to provide comprehensive treatments when individuals have co-occurring
psychiatric or general medical conditions that significantly influence
relapse risk (e.g., chronic pain, depression, anxiety, impaired
cognition, and impulse control disorders) (22–24).
The term "substance use disorder" encompasses
a number of different substances and disorders (i.e., abuse, dependence,
intoxication, withdrawal, and psychiatric syndromes and disorders
that result from substance use). Substance abuse and substance dependence are
two disorders that are frequently encountered, and their criteria
are applicable across substances. The criteria for these disorders
are presented in Tables 1 and 2. However, it is beyond the scope
of this practice guideline to describe all the substance use disorders,
and the reader is referred to DSM-IV-TR for a full description.
A clinician's approach to assessing a substance use
disorder will differ depending on the context in which an individual
presents for treatment. An individual who recognizes the presence
of a substance use disorder may present willingly for treatment
and be amenable to a thorough assessment (as outlined below). However,
many individuals will not be similarly motivated, and retaining
them in treatment may require adapting the assessment process to
their level of insight and motivational state. For example, individuals
with benzodiazepine dependence will often present for treatment
of an anxiety disorder but have no motivation to reduce their benzodiazepine
use. Likewise, individuals with bipolar disorder will often present
with a co-occurring substance use disorder but may not identify
or recognize substance use as problematic (e.g., the use of alcohol
at night to facilitate sleep onset). In such cases, educational
efforts to help the individual recognize the substance use disorder
as a problem may be helpful. This may involve extending the assessment
phase over time rather than attempting to acquire all the patient's
information at once so that the clinician can tailor the intervention
to the patient's particular stage of change (25).
In an alternative scenario, an individual may be coerced into
an assessment by frustrated family members or drug treatment diversion
programs within the justice system. Such individuals may be resentful
of the assessment process and have no motivation for changing their
behavior other than the stipulations of family or the court system.
Under these conditions, the clinician must attempt to establish
an alliance with the individual in order to be viewed as a valuable
source of information and aid rather than as a punitive extension
of the referring sources. Retaining the individual in treatment
will also take precedence over treating the disorder but may not
always be possible. A full assessment of the individual's substance
use disorder(s) may need to be gathered in pieces over time, with
details being added to the initial picture when the individual is
more comfortable sharing information pertinent to the pattern of
his or her substance use and more motivated to contemplate change.
All individuals undergoing a psychiatric evaluation should
be screened for a substance use disorder, regardless of their age,
presentation, or referral source. Several empirically validated
screening tools are available that do not require extensive training
or time to use during an initial assessment. Commonly used screens
include the four-item CAGE screen for alcohol abuse (Have you ever
felt the need to Cut down on drinking,
been Annoyed by others' criticism
of your drinking, felt Guilty about
drinking, needed an Eye-opener drink
first thing in the morning?) (26), the 10-item Alcohol Use Disorders Identification
Test (27), and the Drug Abuse Screening Test, a 20-item self-report
assessment that screens for commonly abused substances other than
alcohol (28). If screening instruments or other assessment questions
reveal that an individual has ever used substances, it is important
to obtain a history of current and past substance use, including
the frequency of substance use and the quantity of the substance
used per using episode. The clinician should also inquire about
the individual's current caffeine and nicotine use, past
cigarette use in pack-years (defined as the number of packs per
day multiplied by the number of years of smoking), and, for current
smokers, the time from waking in the morning to their first cigarette.
It is also important for the assessing clinician to inquire
about specific substance misuse if an individual's work
is associated with increased risk because of occupational demands, privileged
access to controlled substances, or a desire to enhance performance.
For example, firefighters, police, and emergency personnel have
a high prevalence of alcohol dependence related to job stress (29).
Misuse of prescription substances or anesthetics is common among
health care or veterinary medicine personnel; when compared with
other physicians who misuse substances, anesthesiologists have been
shown to be more likely to misuse opioids (30). Synthesis and misuse
of controlled substances have also been observed in medicinal chemists.
Anabolic steroid hormone precursors may be misused by athletes,
and stimulant drugs may be misused by commercial truck drivers attempting
to stay awake longer or by models and actors wanting to lose weight.
Cocaine use appears to be a hazard among staff in restaurants and
the entertainment industry. The clinician will also want to ask
about other situations in an individual's history that
may put him or her at higher risk for substance misuse, such as
a history of trauma, psychiatric disorders, or chronic medical conditions.
In evaluating an individual with a suspected or confirmed
substance use disorder, a comprehensive psychiatric evaluation is
essential. Information should be sought from the individual and,
with the individual's consent, available family members
and peers, current and past health professionals, employers, and
others as appropriate. The goals of the assessment are to establish
a multiaxial DSM-IV-TR diagnosis, including identification of current
and past substance use disorders as well as other comorbid psychiatric
and physical disorders, and to identify other factors that are important
to developing a treatment plan. Specific elements of the assessment
may include the following:
- A systematic inquiry
into the mode of onset, quantity, frequency, and duration of substance
use; the escalation of use over time; the motivation for use; the
specific circumstances of the individual's substance use
(e.g., where, with whom, how much, by what route of administration);
the desired effect of the substance used; the most recent dose of
each substance used; the time elapsed since the most recent use;
the degree of associated intoxication; the severity of associated
withdrawal syndromes; and the subjective effects of all substances
used, including substances other than the individual's "drug
of choice." As the psychiatrist elicits the individual's
substance use history, he or she should also determine if the individual
meets DSM-IV-TR criteria for abuse or dependence (see Tables 1 and 2) for each substance used. Because many patients entering treatment
for a specific substance use disorder are using more than one substance,
assessment should routinely include questions about the use of multiple
substances, including which substances are used in combination, in
what order, and for what effect. Use of over-the-counter and prescription
medications should also be ascertained. If prescription medications
are being used, it is important to learn if the medication has been
prescribed for the individual or for someone else.
- A history of any prior treatment for a substance use
disorder, including the characteristics of the treatment such as
setting; context (e.g., voluntary or involuntary); modalities used;
duration and, if applicable, dose of treatment; adherence to treatment;
and short-term (3-month), intermediate (1-year), and longer-term
outcomes as measured by subsequent substance use, level of social
and occupational functioning achieved, and other outcome variables.
Previous efforts to control or stop substance use outside of a formal
treatment setting should also be discussed. For individuals who
had previous treatment or periods of abstinence, additional history
may include the duration of abstinence, the factors that promoted
or helped sustain abstinence, the impact of abstinence on psychiatric
functioning, the circumstances surrounding relapse (e.g., whether
the relapse was related to withdrawal symptoms, exacerbation of
a psychiatric disorder, or psychosocial stressors), the individual's
attitude toward prior treatment, nontreatment experiences, and expectations
about future treatments.
- A comprehensive general medical and psychiatric history,
including mental status and physical examination, to ascertain the
presence or absence of co-occurring psychiatric or general medical
disorders as well as signs and symptoms of intoxication or withdrawal. Psychological
or neuropsychological testing may also be indicated for some individuals (e.g.,
to assess an individual's level of cognitive impairment).
When a clinician is attempting to ascertain an individual's
current medication use, he or she should specifically ask about
prescribed and nonprescribed medications, including vitamins and
herbal products.
- Qualitative and quantitative blood and urine screening
for substances of abuse and laboratory tests for abnormalities that
may accompany acute or chronic substance use. These tests may also
be used during treatment to monitor for potential relapse. For some
substances, such as alcohol and nicotine, breath tests may also
be useful.
- Screening for infectious and other diseases often found
in substance-dependent individuals (e.g., human immunodeficiency
virus [HIV], tuberculosis, hepatitis). Such individuals, particularly
those with evidence of compromised immune function, are at high
risk for these diseases.
- A complete family and social history, including information
on familial substance use or other psychiatric disorders; social
factors contributing to the development or perpetuation of the substance
use disorder (e.g., social facilitation of substance use); financial
or legal problems; social supports, including peer relationships;
school or vocational adjustment; and other functional impairments.
When obtaining the family and social history, the psychiatrist may
also wish to ask for permission to speak to family members, friends, or
other significant people in the individual's life who may
be able to provide important information regarding the individual's
substance use disorder. In evaluating the impact of the individual's
current living environment on his or her ability to adhere to treatment
and refrain from substance use, it is important to determine whether
and how household members and friends have supported or interfered
with prior attempts at abstinence. The substance use status of others
in the household and close friends (e.g., never used substances,
former substance user, current substance user) should also be considered.
If others in the household are currently using substances, their
willingness to quit at the same time as the individual or to refrain
from substance use in the presence of the individual should be assessed.
- Individual preferences, motivations, and barriers for
treatment. Individuals vary in their treatment preferences regarding
pharmacotherapy, group therapy, individual therapy, and self-help
treatments. Working with the individual's preferences is
likely to lead to better treatment adherence and outcomes (31).
For individuals who have a co-occurring psychiatric disorder, exacerbation
of psychiatric symptoms can be an additional barrier (31, 32).
When a clinician is assessing a new patient and establishing
a diagnosis, it is often difficult to distinguish between psychiatric
symptoms resulting from substance use and those from a co-occurring
psychiatric disorder. Anxiety, depression, mania, and psychosis
are all commonly induced by various substances and can be observed
with chronic use as well as during specific substance-induced states,
including intoxication and withdrawal. Evaluation of psychiatric
symptoms in substance-using individuals can be enhanced with repeated,
longitudinal psychiatric assessments. As part of the initial assessment,
it may also be useful to draw a timeline of all substances used
and all psychiatric symptoms and/or disorders and to include
in this timeline all prior treatments. This timeline approach can
help determine the chronology of symptom development (i.e., whether
the signs and symptoms predate or follow the onset of repetitive
substance use), the presence or absence of symptoms during extended
substance-free periods (e.g., 3 months or more), and the impact
of each disorder on the presentation, clinical course, and outcome
of the other(s).
The probability that an individual with a substance use disorder
has a co-occurring psychiatric disorder and not a substance-induced
psychiatric disorder is increased if at least one first-degree relative
has a documented history of a similar disorder, the individual's
symptoms are not typically observed in conjunction with the use
of a particular substance, there is a clear history that psychiatric
symptoms preceded the onset of the substance use disorder, or the
symptoms were evident during extended substance-free periods. Such
a distinction is relevant when a clinician must decide whether to
treat the psychiatric symptoms with medications and determine how
long to maintain a medication once it is started. For example, individuals
with certain substance-induced psychotic symptoms, such as paranoia
resulting from the use of stimulants or phencyclidine (PCP), may
benefit from the short-term use of an antipsychotic medication.
Conversely, symptoms of depression and anxiety coexisting with a
substance use disorder may initially be addressed in psychosocial
treatment but may require medication management if they do not improve
over time.
Individuals with substance use disorders may receive care
in a variety of settings. Treatment settings vary according to the
availability of resources (e.g., the presence or absence of medical
monitoring, the specialization of services and therapy provided,
the availability of psychiatric consultation), the freedom allowed
the individual (e.g., locked versus open unit), the intensity of
treatment duration/participation, and the milieu philosophy
driving the primary interventions (e.g., medical model, educational,
12-step, peer support, faith based). Because treatment best occurs
in a system that encourages cessation of all harmful substance use
(33), consideration should be given to making treatment sites smoke
free (33, 34). Although most studies indicate that smoking cessation
does not increase alcohol relapse and may aid recovery in substance-dependent
patients (35–37), one study found that smoking cessation
worsened drinking outcomes in a group of alcohol-dependent patients (38).
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1. Factors affecting choice of treatment setting
Individuals should be treated in the least restrictive setting
that is likely to prove safe and effective. Decisions regarding
the site of care should be based on the individual's 1)
capacity and willingness to cooperate with treatment; 2) ability
for self-care; 3) social environment (which may be supportive or
high risk); 4) need for structure, support, and supervision to remain
safe and abstinent; 5) need for specific treatments for co-occurring
general medical or psychiatric conditions; 6) need for particular
treatments or an intensity of treatment that may be available only
in certain settings; and 7) preference for a particular treatment setting.
In addition, the choice of setting should be guided by the particular
substance(s) used, the medical risks associated with use of the
substance(s), the accessibility of appropriate levels of care, and
the stated goals of the individual's treatment plan (as
described in Sections III through VII and as determined by the individual's
clinical status).
Patients should be moved from one level of care to another
on the basis of these factors; the decision to move to a less intensive
level of care should consider these factors plus the clinician's
assessment of a patient's readiness and ability to benefit
from the less restrictive setting. To appropriately match patients
and treatment settings, many clinicians, health insurers, hospitals,
and treatment agencies use the American Society of Addiction Medicine (ASAM)
patient placement criteria (39). These criteria provide an algorithm
for placement that represents expert consensus and that is updated
as additional evidence becomes available on treatment outcomes and
levels of care.
Studies comparing the short-term, intermediate, and long-term
benefits of treatment in various settings (i.e., inpatient, residential,
partial hospitalization, outpatient) have a variety of methodological
problems, including heterogeneity of individual populations, high
dropout rates, lack of controlled trials, inappropriate comparison
of outcomes after time-limited treatment interventions, and reliance
on individual self-reports uncorroborated by data from collateral
sources (40). Stated treatment goals, program features, and outcome
measures vary across studies (41). A common finding among different
treatments available for substance use disorders is that retention
in treatment improves outcomes (42–45).
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2. Commonly available treatment settings and services
Settings and services used in the treatment of substance use
disorders may be considered as points along a continuum of care
from most to least intensive. The specific factors leading to the
choice of a particular setting for an individual patient are described
below. The choice of a treatment setting may also be influenced
by availability, given that communities differ in the variety of
treatment services they offer and certain specialized treatment
settings (e.g., dual-diagnosis partial hospitalization care) may
not be widely available. For individuals with primary nicotine dependence
or marijuana use disorders, treatment occurs in outpatient settings;
information presented about other treatment settings may not be
applicable to these populations.
The range of services available in hospital-based programs
typically includes emergency detoxification and stabilization during
withdrawal; assessment and treatment of general medical and psychiatric
conditions; group, individual, and family therapies; psychoeducation;
motivational counseling; and social service facilitation of follow-up
care in available community services (46, 47). Psychiatric hospitals
may offer dual-diagnosis inpatient units that specialize in the
stabilization of co-occurring psychiatric and substance use disorders. For
patients admitted to hospital-level care for other reasons (general
medical or psychiatric), smoking cessation programs may also be
available.
Hospital-based treatment settings may be secure (i.e., locked)
or may permit individuals and visitors to come and go in a monitored
but generally less restrictive fashion. Secure hospital settings
should be considered for individuals with co-occurring psychiatric
conditions whose clinical state would ordinarily require such a
unit (e.g., actively suicidal individuals). Individuals with poor
impulse control and judgment who in the presence of an "open
door" are likely to leave the program or obtain or receive
drugs on the unit are also candidates for a secure unit. In some
states, individuals can reside on a secure unit in "conditional
voluntary" status, which requires written notice and a
time delay (e.g., 3 days) before the patient's request
for discharge is approved or another disposition (e.g., commitment)
is implemented. Such restrictions can provide a useful period of
delay in which poorly motivated individuals can reconsider their
wish to leave a program prematurely.
The available data do not support the notion that hospitalization
per se has specific benefits over other treatment settings beyond
the ability to address treatment objectives that require a medically
monitored environment (48, 49). There is consensus (e.g., ASAM patient placement
criteria) that individuals in one or more of the following categories
may require hospital-level care:
- Individuals with drug
overdoses who cannot be safely treated in an outpatient or emergency
department setting (e.g., individuals with severe respiratory depression,
individuals in a coma)
- Individuals in withdrawal who are at risk for a severe
or complicated withdrawal syndrome (e.g., individuals dependent
on multiple substances, individuals with a history of delirium tremens)
or cannot receive the necessary medical assessment, monitoring,
and treatment in a less intensive setting
- Individuals with acute or chronic general medical conditions
that make detoxification in a residential or ambulatory setting
unsafe (e.g., individuals with severe cardiac disease)
- Individuals with a documented history of not engaging
in or benefiting from treatment in a less intensive setting (e.g.,
residential, outpatient)
- Individuals with marked psychiatric comorbidity who
are an acute danger to themselves or others (e.g., individuals who
have depression with suicidal thoughts, acute psychosis)
- Individuals manifesting substance use or other behaviors
who are an acute danger to themselves or others
- Individuals who have not responded to less intensive
treatment efforts and whose substance use disorder(s) poses an ongoing
threat to their physical and mental health
In general, the duration of hospital-based treatment should
be dictated by the individual's current need to receive
treatment in a restrictive setting and his or her capacity to access,
safely participate in, and benefit from treatment in a less restrictive
setting.
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b) Partial hospitalization
programs and intensive outpatient programs
Partial hospitalization and intensive outpatient programs
can provide an intensive, structured treatment experience for individuals
with substance use disorders who require more services than those
generally available in traditional outpatient settings. Although
the terms "partial hospitalization," "day
treatment," and "intensive outpatient" programs
may be used nearly interchangeably in different parts of the country,
the ASAM patient placement criteria (39) define structured programming
in partial hospitalization programs as 20 hours per week and in
intensive outpatient programs as 9 hours per week. Partial hospitalization programs
provide ancillary medical and psychiatric services, whereas intensive
outpatient programs may be more variable in the accessibility of
these services. Some patients enter these programs directly from
the community. Alternatively, these programs are sometimes used
as "step-down" programs for individuals leaving
hospital or residential settings who are at a high risk of relapsing
because of problems with motivation, the presence of frequent cravings
or urges to use a substance, poor social supports, immediate environmental
cues for relapse and/or availability of substances, and
co-occurring medical and/or psychiatric disorders. The
goal of such a "step-down" approach is to stabilize
patients by retaining them in treatment and providing more extended
intensive outpatient monitoring of relapse potential and co-occurring
disorders. Partial hospitalization and intensive outpatient programs
may also be used as a brief "step-up" in treatment
for an outpatient who has had a relapse but who does not require
medical detoxification or who has entered into a high-risk period
for relapse because of life circumstances or recurrence of a co-occurring
medical and/or psychiatric symptom (e.g., depressed mood,
increased pain).
The treatment components of partial hospitalization programs
may include some combination of individual and group therapy, vocational
and educational counseling, family meetings, medically supervised
use of adjunctive medications (e.g., opioid antagonists, antidepressants),
random urine screening for substances of abuse, and treatment for
any co-occurring psychiatric disorders. Intensive outpatient programs
use individual therapy, group therapy, family therapy, and urine
toxicology but vary in the amount of other therapeutic components
used (50). An advantage of intensive outpatient programs is the
availability of evening programs that accommodate day-shift employees.
The availability of weekend programs varies for both partial hospitalization
and intensive outpatient programs. Both kinds of programs aim to
prepare the individual for transition to less intensive outpatient
services and increased self-reliance through the practice and mastery
of relapse prevention skills and the active use of self-help programs.
Limited data are available for the efficacy of partial hospitalization
and intensive outpatient programs. Randomized, controlled trials
have demonstrated that some individuals who would ordinarily be
referred for residential- or hospital-level care do just as well
in partial hospitalization care (51, 52). One study (53) comparing
a more time-intensive day hospital program to an intensive outpatient
program that was actually less time intensive found no differences
in outcome for cocaine-dependent individuals, and another study comparing
intensive with traditional outpatient treatment of the same population
found no differences in outcome (54).
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c) Residential treatment
Residential treatment is indicated primarily for individuals
who do not meet clinical criteria for hospitalization but whose
lives and social interactions have come to focus exclusively on
substance use and who currently lack sufficient motivation and/or
substance-free social supports to remain abstinent in an ambulatory
setting. For these individuals, residential facilities provide a
safe and substance-free environment in which residents learn individual
and group living skills for preventing relapse. As in the case of
hospital-based programs, residential treatment programs frequently
provide psychosocial, occupational, and family assessment; psychoeducation;
an introduction to self-help groups; and referral for social or
vocational rehabilitative services where necessary (55). Many residential
programs provide their own individual, group, and vocational counseling
programs but rely on affiliated partial hospitalization or outpatient
programs to supply the psychosocial and psychopharmacological treatment
components of their programs. Residential treatment settings should
have access to general medical and psychiatric care that is required
to meet individual needs.
The duration of residential treatment should be dictated by
the length of time necessary for the patient to meet specific criteria
that would predict his or her successful transition to a less structured,
less restrictive treatment setting (e.g., outpatient care). These
criteria may include a demonstrated motivation to continue in outpatient
treatment, the ability to remain abstinent even in situations where
substances are potentially available, the availability of a living
situation and associated support system conducive to remaining substance
free (e.g., family, substance-free peers), sufficient stabilization
of any co-occurring general medical or psychiatric disorder so that
the patient is considered suitable for outpatient aftercare, and the
availability of adequate follow-up care.
In some areas, particularly urban centers, residential treatment
programs specifically designed for adolescents, pregnant or postpartum
women, or women with young children are available (56, 57).
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d) Therapeutic communities
Individuals with opioid, cocaine, or multiple substance use
disorders may benefit from referral to a long-term residential therapeutic
community. These programs are generally reserved for individuals
with a low likelihood of benefiting from outpatient treatment, such as
individuals who have a history of multiple treatment failures or
whose profound impairment in social relational skills or ability
to attain and sustain employment impede adherence to outpatient
treatment (58). Rather than viewing substance abuse as an illness
(as defined by the disease concept), therapeutic community theory
views it as a deviant behavior; that is, it is seen as a symptom
of pathological development in personality structure, social relating,
and educational and economic skills (reviewed by De Leon in reference
59). The therapeutic community milieu provides individual, social,
and vocational rehabilitation through the community method of social
learning. It is a highly structured, substance-free community setting
in which the primary interventions are behavioral modeling, supportive
peer confrontation, contingency management, community recreation,
and work therapy designed to facilitate adherence to social norms
and substance-free lifestyles (44).
Therapeutic communities are characteristically organized along
strict hierarchies, with newcomers being assigned to the most menial
social status and work tasks. Residents achieve higher status and
take on increasing responsibility as they demonstrate that they can
remain substance free and conform to community rules. Supportive
confrontation, individually and in groups, is a primary intervention
used to break through denial about the role of substance use in
one's life, identify maladaptive behaviors and coping styles
that lead to interpersonal conflict and vocational failure, suggest
alternative ways of handling disturbing affects, and encourage the
development of attitudes and beliefs that are incompatible with
continued substance use.
Data regarding the effectiveness of traditional long-term
(2-year commitment) therapeutic communities are limited by the fact
that only 15%–25% of individuals admitted
voluntarily complete a program, with maximum attrition occurring
in the first 3 months (60, 61). Retention rates differ with program
sites (62), and retention lengths predict outcomes on abstinence
and lack of criminal recidivism indexes, with 2-year postcompletion
success rates at 90% for graduates, 50% for dropouts
completing >1 year, and 25% for dropouts completing <1
year (44, 63).
Cost-containment concerns and increasing knowledge of dual-diagnosis
needs have led to modifications of the traditional therapeutic community
model. Shorter-term programs (e.g., 3–12 months) and nonresidential
programs are offered for those with fewer social and vocational
impairments. The expanded availability of social services has allowed
improved treatment of special populations (e.g., dual-diagnosis,
HIV-positive, single-parent, adolescent) in the therapeutic community
setting, and some methadone maintenance programs are provided in
this setting.
Potential voluntary applicants to a residential therapeutic
community setting should have some understanding of the severity
of their substance use disorder and a readiness to change their
lifestyle; they should also have a willingness to conform to the
structure of the therapeutic community and to temporarily sever
ties with family and friends while they assimilate into the community
environment. An individual's violation of community rules
or shirking of work responsibilities is disclosed to all community
members and may be grounds for discharge.
Therapeutic community settings have provided some of the better
studied and more successful programs for treating incarcerated substance
abusers (64). This has influenced the development of standardized
staff training curricula (65).
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e) Community residential
facilities
Community residential facilities are commonly known as "halfway
houses" or "sober houses," with the former
typically offering more structure and supervision. They provide an
outpatient substance-free housing environment as a transitional
setting for individuals in recovery who are not yet able to manage
independent housing without a significant risk for relapse. Some
studies have shown that for patients with multiple service needs
(e.g., vocational, housing, transportation), the provision of stable
housing in the form of long-term community residential facilities
leads to significantly improved substance use outcomes (66–68).
This benefit has been demonstrated for adult substance users of
both sexes. Community residential facilities show more variability
in substance use outcomes for youth and adolescents (69); this may
be related to inadequate matching of services to individual needs.
Aftercare occurs after an intense treatment intervention (e.g.,
hospital or partial hospitalization program) and generally includes
outpatient care, involvement in self-help approaches, or both. The
clinician should consider the possibility that cognitive impairment may
be present in recently detoxified patients when determining their
next level of care. Research on aftercare has examined different
treatment models, including eclectic, medically oriented, motivational,
12-step, cognitive-behavioral, group, and marital strategies (see
Section II.F). Given the chronic, relapsing nature of many types
of substance use disorders, especially those requiring hospitalization,
it is expected that aftercare will be recommended with few exceptions.
In fact, if addiction is reconceptualized along the lines of a chronic
rather than an acute disease model, as recommended by McLellan et
al. (4), the distinction between a "treatment episode" and "aftercare" should
be removed and the different modalities of care (e.g., inpatient,
outpatient) be reconsidered as part of a continuous, long-term treatment
plan.
Outpatient treatment settings include but are not limited
to mental health clinics, integrated dual-diagnosis programs, private
practice settings, primary care clinics, and substance abuse treatment
centers, including opioid treatment programs. For individuals with primary
nicotine dependence or a marijuana use disorder, treatment is always
provided in an outpatient setting. For individuals with other substance
use disorders, outpatient treatment is appropriate when clinical
conditions or environmental and social circumstances do not require
a more intensive level of care.
As in other treatment settings, the optimal outpatient approach
is a comprehensive one that includes a variety of psychotherapeutic
and pharmacological interventions along with behavioral monitoring,
where indicated. The evidence base for empirically supported outpatient
treatments is larger for alcohol, nicotine, and opioid dependence
treatments than for other substance dependence treatments (70–74).
In addition to medication therapies (see Section II.E), outpatient
treatments with strong evidence of effectiveness include CBTs (e.g.,
relapse prevention, social skills training), MET, behavioral therapies
(e.g., community reinforcement, contingency management), TSF, psychodynamic
therapies/IPT, self-help manuals, behavioral self-control,
brief interventions, case management, and group, marital, and family
therapies (see Section II.F).
Many specific outpatient treatments have been designed to
enhance an individual's participation in treatment and
sense of self-efficacy regarding the reduction or cessation of problematic
substance use. As in the case of residential and partial hospitalization
programs, high rates of attrition can be problematic in outpatient
settings, particularly in the early phase (i.e., the first 6 months).
Because intermediate and long-term outcomes are highly correlated
with retention in treatment, individuals should be strongly encouraged
to remain in treatment (42, 43, 45). Clinicians should also encourage
and attempt to integrate into treatment a patient's participation
in self-help programs where appropriate (see Section II.F.9) (75).
Case management, by definition, exists as an adjunctive treatment.
The goals of case management interventions are to provide advocacy
and coordination of care and social services and to improve patient
adherence to prescribed treatment and follow-up care (76). Case
management initially provides psychoeducation about the patient's
diagnosis and treatment as well as assessment and stabilization
of basic necessities required for the individual to actively participate
in treatment (e.g., housing, utilities, income, health insurance, transportation).
Beyond this, case managers aid individuals in maintaining stability
and understanding and adhering to prescribed treatment. The variability
in case management models has complicated research on the effectiveness
of this approach (77, 78). Nevertheless, studies show that case
management interventions are effective for individuals with an alcohol
use disorder (79) or co-occurring psychiatric and substance use
disorders (80) and for adolescents with substance use disorders
(81).
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i) Legally mandated
treatment
Treatment of substance use disorders may be legally mandated
under a variety of circumstances, including substance-related criminal
offenses such as driving under the influence of alcohol or drugs.
Drug court programs recognize the effectiveness of diverting offenders
with lesser drug-related convictions from correctional facilities
into court-mandated community programs for the treatment of substance
use disorders (82). Standard procedures for drug court programs
include 1) assessment of individual substance use treatment needs,
2) appropriate referral for treatment after arrest, 3) periodic
monitoring of adherence to treatment through the use of clinician
report and mandatory drug testing, 4) reduction in the severity
of charges contingent on successful utilization of programs for
the treatment of substance use disorders, and 5) aftercare planning
for maintaining sobriety in the community. For offenses related
to driving under the influence of alcohol or drugs, state and community
sanctions include incarceration, license suspension, driver's
education, and community service requirements. Some evidence indicates
that more severe sanctions lead to less recidivism for intoxicated
drivers with high blood alcohol content readings (83).
Despite the high frequency at which substance use disorders
and criminal behaviors co-occur, it has been estimated that only
1%–20% of substance abusers receive adequate
treatment while incarcerated (84). The most studied effective treatment
programs for incarcerated individuals are therapeutic communities
(see Section II.C.2.d) (64).
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j) Employee assistance
programs
Employee assistance programs (EAPs) provide an employment-based
treatment setting and referral platform for employees with substance
use disorders. EAPs differ according to workplace size and location.
A critical difference for substance use treatment received through
an EAP versus through an alternate community outpatient setting
is the definition of successful intervention outcome. Whereas most
community settings define successful outcome as a reduction of substance
use and related medical and social problems, an EAP defines and
measures success primarily through job performance. This reflects
the employer's need to serve and retain an employee while
simultaneously protecting the workplace from inadequate job performance
and attributable losses (85). EAPs are cost-effective in the short
term (86, 87), but posttreatment follow-up rates are poor (88).
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D. Psychiatric Management
Successful treatment of substance use disorders may involve
the use of multiple specific treatments, the choice of which may
vary for any one individual over time, and may involve clinicians
from a variety of backgrounds. Psychiatric management entails the
ongoing process of choosing from among various treatments, monitoring
patients' clinical status, and coordinating different treatment
components. The frequency, intensity, and focus of psychiatric management
must be tailored to meet each patient's needs, and the
type of management is likely to vary over time, depending on the
patient's clinical status.
In recent years, there has been a great deal of research and
clinical emphasis on the clinician's role in motivating
patients with substance use disorders to change their behaviors. Motivational
interviewing techniques (49) were developed specifically for the
treatment of patients with a substance use disorder. These involve
the use of an empathic, nonjudgmental, and supportive approach to
examining the patient's ambivalence about changing addictive
behaviors. Understanding the patient's stage of readiness
to change (precontemplation, contemplation, preparation, action,
or maintenance stage) (25) allows the clinician to determine what
motivational strategies are most appropriate for the patient at
that time. One of the goals of motivational interviewing is to elicit
the patient's reasons for change and assist the patient
in moving through the subsequent stages of change (89).
Other techniques involved in motivating change include A-FRAMES
(see Section II.F.10) and METs. Manuals describing these techniques
are available (49, 90).
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2. Establishing and
maintaining a therapeutic framework and alliance
An essential feature of psychiatric management of patients
with a substance use disorder is the establishment and maintenance
of a therapeutic alliance wherein the psychiatrist empathically
obtains the necessary diagnostic and treatment-related information,
gains the confidence of the patient and perhaps significant others,
and is available in times of crisis. The frequency and duration
of treatment contacts should be sufficient to engage the patient and,
where appropriate, significant others in a sustained effort to participate
in all relevant treatment modalities and, where appropriate, self-help
groups. Within the context of this alliance, the primary goal of
treatment is to help the patient learn, practice, and internalize changes
in attitudes and behaviors that are conducive to relapse prevention
(91, 92). The strength of the therapeutic alliance has been found
to be a significant predictor of psychotherapy outcome (93). For
example, several studies of individuals with substance use disorders
have found that a stronger patient-clinician alliance predicts less
substance use and better psychological functioning by the patient
(94–96), although one of these studies found no association
between therapeutic alliance strength and treatment retention for
patients enrolled in a methadone maintenance program (96). Despite
the finding of this one study, the chronic and relapsing nature
of substance use disorders highlights the importance of establishing
a therapeutic relationship so that patients will return for additional
treatment, if necessary (33, 97–99). Ackerman and Hilsenroth
(100) reviewed therapist attributes and strategies that facilitate
a positive therapeutic alliance for all patient populations. They found
that being flexible, honest, respectful, confident, warm, and open
all contributed to the development of a positive therapeutic alliance.
The most effective strategies for developing such an alliance included
exploration, reflection, highlighting past therapy successes, providing
accurate interpretation, facilitating the expression of affect,
and attending to the patient's experience.
A review of the literature on effective characteristics of
therapists concluded that the characteristic most associated with
patient retention and reduced substance use is strong interpersonal
skills (101). Safran and Muran (102) reviewed techniques for repairing
ruptures in the therapeutic alliance, such as clarifying misunderstandings,
helping patients learn that they can express their needs in an individuated
fashion and assert themselves without destroying the therapeutic
relationship, and changing the tasks and goals to be more relevant to
the patient's current needs. Limit setting has an important
role in treatment of substance use disorders and may be particularly
important for individuals with co-occurring personality disorders
(103, 104).
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3. Assessing safety
and clinical status
The psychiatric assessment establishes a diagnosis and provides
a baseline determination of a patient's clinical status.
Ongoing evaluation of the patient's safety is also critical, as
the patient's clinical status may change over time. It
is particularly important to assess patients for suicidal or homicidal
thoughts or other dangerous behaviorsuch as driving while
under the influence of substances, domestic violence, or child abuse
or neglectthat may need to be addressed through a change
in the treatment plan or care setting.
Because relapse to substance use is common and inconsistently
reported by patients (particularly when use is met with negative
consequences or a judgmental response), breath, blood, saliva, and
urine testing are helpful in the early detection of relapse. These tests
are often initially conducted on a frequent and random schedule,
as many substances and their metabolites may be detected for only
a few days after use. Random urine screening for recent (i.e., within
the last 1–3 days) substance use may be supplemented by
nonrandom testing when recent substance use is suspected.
Methods of urine screening vary as to levels of sensitivity,
specificity, and cost. The psychiatrist should be familiar with
the applicability and sensitivity of the available analytic methods
and collection procedures used in local laboratories, and he or
she should specify the suspected type of substance used when requesting
testing. Direct supervision of a patient's voiding or the
use of other procedures (e.g., temperature-sensitive cups) will
help to increase the validity and reliability of the test results.
The decision to test a patient's breath, blood, or
urine depends on the type of substance use suspected, the substance's
duration of action, the sensitivity of the test used, and the clinical
setting in which care is being rendered. For example, blood testing
is useful for assessing very recent substance use because it reflects
current blood levels, and breath testing is useful for detecting
alcohol intoxication and generally gives results comparable to those from
blood tests. However, breath testing for alcohol is frequently preferred
because the results are immediate and it is a noninvasive and low-cost
procedure. Breath testing can also detect carbon monoxide, an indicator
of smoking, as recent as a few hours before the test (105).
Urine testing is useful for detecting substance use over the
preceding 5-day period for common substances of abuse (cocaine,
opiates, cannabis, amphetamines, benzodiazepines, and PCP); however,
certain opioids (buprenorphine, oxycodone, hydrocodone, and fentanyl)
cannot be detected with routine methods and require special assays.
Alcohol can be detected for up to 24 hours in urine, whereas ethyl
glucuronide (EtG), a minor metabolite of alcohol, can be detected
in the urine for 2–3 days after alcohol ingestion (106–108).
Because EtG is produced by in vivo metabolism of alcohol prior to
excretion in urine, the assay for EtG is highly sensitive and specific
and is sometimes used in monitoring programs. Finally, there is
some evidence that certain state markers can be used to detect recent
alcohol use (e.g., elevation of carbohydrate-deficient transferrin,
mean corpuscular volume, or 
-glutamyl
transpeptidase).
Results from some studies have indicated that more intensive
monitoring of substance use may increase recovery rates from a substance
use disorder, as has been demonstrated with physicians and pilots
(109–111). Ongoing assessment of the substance use disorder and
psychiatric status is also necessary to ensure that the patient
is receiving the appropriate treatment(s) and to monitor the patient's
response to treatment (i.e., to determine the optimal dose of a
medication, evaluate its efficacy, and detect treatment-emergent
side effects). Co-occurring psychiatric disorders may complicate
the treatment of the substance use disorder (111) and require the
addition of specific treatments (e.g., an antidepressant medication
for a patient with co-occurring major depressive disorder). An ongoing
longitudinal assessment of the patient may be critical to the accurate
diagnosis of a co-occurring condition (see Section II.B).
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4. Managing intoxication
In general, acutely intoxicated patients require a safe, monitored
environment in which they can receive decreased exposure to external
stimulation, as well as reassurance, reorientation, and reality
testing. Clinical assessment involves ascertaining which substances have
been used; the route of administration, dose, and time since the
last dose; whether the level of intoxication is waxing or waning;
and other diagnostic information, as has been already described.
Management of acute intoxication may also be directed toward hastening the
removal of substances from the body, which may be accomplished through
gastric lavage (in the case of substances that have been recently
ingested) or techniques that increase the excretion rate of substances
or their active metabolites. Medications that antagonize the actions
of the abused substances may be used to reverse their effect. Examples
include the administration of naloxone to patients who have overdosed
with heroin or other opioids or flumazenil to patients who have
overdosed with benzodiazepines.
Many patients use multiple substances simultaneously to enhance,
ameliorate, or otherwise modify the degree or nature of their intoxication
or to relieve withdrawal symptoms. Intoxication with alcohol and
cocaine, the use of heroin and cocaine ("speedball"),
and the combined use of alcohol, marijuana, and/or benzodiazepines
by opioid-dependent patients are particularly frequent. When intoxication
with multiple substances is present, the effects of each substance
need to be taken into consideration in managing the patient. More
information on the management of alcohol, cocaine, and opioid intoxication
can be found in the specific section for each substance (Sections
IV.C.1, VI.C.1, and VII.C.2, respectively).
Not all individuals who are intoxicated or using substances
will develop withdrawal symptoms. Withdrawal syndromes usually occur
in physically dependent individuals who discontinue or reduce their
substance use after a period of heavy and regular use. Patients using
multiple substances (including alcohol and nicotine) are at risk
for withdrawal from each substance. Factors that predict the severity
of a withdrawal syndrome include 1) type of substance used, 2) time
elapsed since last use, 3) metabolic rates of the substance, 4)
dissociation rates of the substance from receptor sites, 5) synergistic
effects or drug-drug interactions from the concomitant use of other
prescribed or nonprescribed medications, 6) the presence or absence
of concurrent general medical or psychiatric disorders, and 7) past withdrawal
experiences (especially for alcohol). More information on the management
of withdrawal from alcohol, cocaine, and opioids can be found in
the specific section for each substance (Sections IV.C.2, VI.C.2,
and VII.C.3, respectively).
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6. Reducing the morbidity
and sequelae of substance use disorders
The clinician should engage the patient and, when appropriate,
significant others in developing a comprehensive treatment plan
to address problems in biological, psychological, and social functioning.
Coordination with a patient's primary care physician may
also be important in the medical management of patients with substance
use disorders (112).
Substance use disorders are commonly associated with substance-related
medical morbidity. Although an individual patient's presentation
may warrant specific screening and intervention, a number of baseline
screening tests are frequently recommended based on epidemiological
studies documenting the high risk for co-occurring medical disorders.
For example, electrolyte panels and complete blood counts may be
considered for those with severe substance dependence of any type
because of the high correlation of substance dependence with poor
nutritional status. For women of childbearing age, testing for pregnancy
is an important part of medical screening. Tuberculin skin testing
may be appropriate because of substance users' increased
risk for tuberculosis exposure and to address public health concerns.
Blood pressure monitoring may be advisable for substance users because of
associated hypertension (e.g., with alcohol, nicotine, and stimulants)
and hypotension (e.g., dehydration associated with poor self-care)
risks. For individuals with specific substance use disorders, additional
laboratory and other screening tests may be considered. These include
the following:
- Alcohol
use. Hepatic panel to screen for liver toxicity
and functioning; complete blood count to determine mean corpuscular
volume, which can be increased with hepatic toxicity, thiamine, folate,
and vitamin B12 deficiency, as well as the
direct effects of alcohol on hematopoiesis; stool sampling for occult
blood reflecting gastritis, peptic ulcerative disease, or esophageal
varices; mental status examination to detect cognitive functioning
deficits
- Nicotine dependence. Examination
of lymph nodes, mouth, and throat to assess for occult cancer and
pulmonary disease; auscultation of chest and lungs; chest X-ray;
pulmonary function testing, if warranted; electrocardiogram because
of increased risk for cardiovascular disease; urine or blood cotinine
level
- Injection drug use. Blood
testing for blood-borne and sexually transmitted diseases, such
as HIV, hepatitis B and C virus, and syphilis; skin examination
for cellulitis; complete blood count to detect occult infection;
genital examination and sampling for chlamydia, gonococcal disease,
and human papilloma virus
Even if not initially caused by substance use, co-occurring
medical disorders may be exacerbated by substance use, such as respiratory
disease worsened by nicotine use; cardiovascular disease worsened
by cocaine, alcohol, or nicotine use; hepatic disease aggravated by
alcohol abuse; and seizure disorder exacerbated by withdrawal from
alcohol, benzodiazepines, or other sedatives. In addition, individuals
with substance use disorders frequently neglect preventive health
care and follow-up medical care (113). All substance use disorders
can be a cause for nonadherence to prescribed medications. Delayed
dosing, missed dosing, or overuse of prescribed medications may
occur during intoxication and withdrawal states. To finance substance
use, individuals may sell prescribed medications (e.g., opiate analgesics)
or avoid filling prescriptions to save insurance copayments. "Downward
drift" and homelessness among substance-dependent individuals
also often curtails their access to medical and dental care.
Individuals with a co-occurring psychiatric disorder are particularly
vulnerable to the self-neglect and morbidity associated with substance
use, possibly resulting in exacerbation of depression and suicidal
thinking, worsening of psychosis, destabilization of bipolar disorder,
and increased impulsivity leading to high-risk behaviors. Nonadherence
to prescribed medication occurs frequently in those with a substance
use disorder and further exacerbates these sequelae. Such individuals
are best served by being referred to an integrated psychiatric and
substance use disorder treatment program (114). Psychiatrists are
often the only medical contacts for patients with co-occurring psychiatric
and substance use disorders and therefore are important resources
for the facilitation of appropriate medical screening, referral
for medical care, and follow-up with medical care (115).
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7. Facilitating adherence
to a treatment plan and preventing relapse
Because individuals with substance use disorders are often
ambivalent about giving up their substance use, it can be useful
to monitor their attitudes about participating in treatment and
adhering to specific recommendations. These patients often deny
or minimize the negative consequences attributable to their substance
use; this tendency is often erroneously interpreted by clinicians
and significant others as evidence of dishonesty. Even patients entering
treatment with high motivation to achieve abstinence will struggle
with the reemergence of craving for a substance or preoccupation
with thoughts about attaining or using a substance. Moreover, social
influences (e.g., substance-using family or friends), economic influences
(e.g., unemployment), medical conditions (e.g., chronic pain, fatigue), and
psychological influences (e.g., hopelessness, despair) may make
an individual more vulnerable to a relapse episode even when he
or she adheres to prescribed treatment. For these reasons, it can
be helpful for clinicians and patients to anticipate the possibility
that the patient may return to substance use and to agree on a corrective
plan of action should this occur. If the patient is willing, it
can be helpful to involve significant others in preventing the patient's
relapse and prepare significant others to manage relapses should
they occur.
Supporting patients in their efforts to reduce or abstain
from substance use positively reinforces their progress. Overt recognition
of patient efforts and successes helps to motivate patients to remain
in treatment despite setbacks. Clinicians can optimize patient engagement
and retention in treatment through the use of motivational enhancement
strategies (49, 116) and by encouraging patients to actively partake
in self-help strategies. Monitoring programs, such as EAPs and impaired-physician
programs (86, 111, 117), can sometimes help patients adhere to treatment.
Early in treatment a clinician may educate patients about
cue-, stress-, and substance-induced relapse triggers (17, 118).
Patients benefit from being educated in a supportive manner about
relapse risk situations, thoughts, or emotions; they must learn
to recognize these as triggers for relapse and learn to manage unavoidable
triggers without resorting to substance-using behaviors. Participation
in AA or similar self-help group meetings can also support patients' sobriety
and help them avoid relapse. Many other strategies can also help prevent
relapse. Social skills training is targeted at improving individual
responsibility within family relationships, work-related interactions,
and social relationships. During the early recovery phase, it can
be helpful to encourage patients to seek new experiences and roles
consistent with a substance-free existence (e.g., greater involvement
in vocational, social, or religious activities) and to discourage
them from instituting major life changes that might increase the
risk of relapse. Facilitating treatment of co-occurring psychiatric
and medical conditions that significantly interact with substance
relapse is a long-term intervention for maintaining sobriety (119–121).
Therapeutic strategies to prevent relapse have been well studied
and include teaching individuals to anticipate and avoid substance-related
cues (e.g., assessing individual capacity to avoid relapse in the
presence of substance-using peers), training individuals how to
monitor their affective or cognitive states associated with increased
craving and substance use, behavioral contingency contracting, training
individuals in cue extinction and relaxation therapies to reduce
the potency of substance-related stimuli and modulate craving intensity, and
supporting patients in the development of coping skills and lifestyle
changes that support sobriety (122, 123). Behavioral techniques
that enhance the availability and perceived value of social reinforcement
as an alternative to substance use or reward for remaining abstinent
have also been used (124).
If relapse does occur, individuals should be praised for even
limited success and encouraged to continue in or resume treatment.
Clinicians may help patients analyze relapses as well as periods
of sobriety from a functional and behavioral standpoint and use
what is learned to adjust the treatment plan to fit the individual's
present needs. For chronically relapsing substance users, medication
therapies may be necessary adjuncts to treatment.
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8. Providing education
about substance use disorders and their treatment
Patients with substance use disorders should receive education
and feedback about their disorder, prognosis, and treatment. Clinicians
are responsible for educating patients and their significant others
about the etiology and nature of substance use, the benefits of
abstinence, the risk of switching addictions (e.g., to other substances,
to addictive behaviors such as compulsive gambling), the identification
of relapse triggers, the availability of treatment options, and
the role of family and friends in aiding or impeding recovery. When appropriate,
psychiatrists may provide education about the effects of alcohol
and other substances on the brain, the positive changes that occur
with abstinence, substance-related medical problems (e.g., hepatitis
C virus), and the effects of smoking, alcohol, and other substances
on fetal development. Education on reducing behavioral harm may
include advice about the use of sterile needles, procedures for
safer sex, contraceptive options, and the availability of treatment
services for drug-exposed newborns. Patients may also be directed
to other educational resources. For example, public health services
for the treatment of nicotine dependence are offered free of charge
and are available by telephone (e.g., the "telephone quitlines" for
individual states sponsored by the Centers for Disease Control and
Prevention [CDC], available at http://www.cdc.gov/tobacco/quitlines.htm),
on the Internet (e.g., the CDC's Tobacco Information and
Prevention Source, available at http://www.cdc.gov/tobacco/),
and by mail. As in all clinical settings, patient education is best
delivered with due consideration to the individual's educational
background and cultural setting.
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9. Facilitating access
to services and coordinating resources among mental health, general
medical, and other service systems
In all aspects of patient management, the psychiatrist may
work collaboratively with members of other professional disciplines,
community-based agencies, treatment programs, and lay organizations
to coordinate and integrate the patient's care and address
the patient's social, vocational, educational, and rehabilitative
needs. This is particularly important for patients lacking resources
or the capacity for self-care because of a psychiatric or medical
disorder. Case management services are aimed at such coordination
of care (125).
In treating an individual with significant comorbidities or
treatment-resistant disorders (e.g., chronic pain syndromes, personality
disorders, cognitive impairment, chronic suicidality), it may be
important for the treating clinician to consult with colleagues
and experts in specialty care. In some cases, it may be necessary
to place patients in a highly supervised setting to protect them
and society from their dangerous behaviors associated with substance
use.
Medication therapies for substance use disorders are effective
adjuncts to behavioral therapies and self-help groups; the settings
for medication therapies include hospitals, partial hospitalization
and intensive outpatient programs, and a variety of outpatient settings including
primary care clinics, mental health clinics, substance use disorder
treatment facilities, and private practice offices.
The types of accepted and effective medication strategies
used in the treatment of specific substance use disorders are discussed
in greater detail in later sections of this practice guideline.
The following sections describe the general principles of these
main categories of medication interventions: 1) medications to treat
intoxication states, 2) medications to treat withdrawal syndromes,
3) agonist maintenance therapies, 4) antagonist therapies, 5) abstinence-promoting
and relapse prevention therapies, and 6) medications to treat co-occurring
psychiatric conditions.
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1. Medications to
treat intoxication states
Most clinicians treating patients with substance use disorders
do not direct medical treatment of life-threatening intoxication
states, because this role belongs to trained emergency physicians.
However, clinicians who treat patients with substance use disorders
should be able to recognize potentially dangerous intoxication states
so they can make a rapid referral to emergency services. This section
briefly describes potentially dangerous states of substance intoxication
and emergency medication therapies.
In general, there are two types of medication interventions
for acute intoxication and overdose: the administration of specific
antagonists (e.g., naloxone for acute opioid overdose, flumazenil
for acute benzodiazepine overdose complicated by ingestion of multiple substances)
and therapies that stabilize the physical effects of substance overdose
(e.g., anticholinergics, adrenergic pressor agents, anti-arrhythmics,
anticonvulsants). Other adjunctive supportive treatments for overdose
include establishing an adequate airway, decreasing the risk of
aspiration (e.g., positioning the patient on his or her side, use
of a cuffed endotracheal tube), and, if indicated, providing ventilatory
support and hemodialysis. Hemodialysis or lavage therapies may also
be used to enhance elimination of ingested substances.
The syndrome of acute opioid overdose is recognizable by respiratory
depression, extreme miosis, and stupor or coma (126). Pulmonary
edema may also be observed. Naloxone is a competitive antagonist
at all three types of opiate receptors (mu, kappa, and sigma) and has
no intrinsic agonist activity (127). It is clinically indicated
to rapidly reverse a known or suspected opioid overdose (126, 128).
Because of its poor bioavailability from significant hepatic first-pass
effects, naloxone is typically administered intravenously, but it
may also be given intramuscularly, subcutaneously, or endotracheally
if intravenous access is unattainable (126). The dosing of naloxone
varies depending on whether the patient is known to be opioid dependent
as well as on the extent of respiratory depression. For example,
in patients with CNS but not respiratory depression, an initial
dose of 0.05–0.4 mg i.v. is recommended. The lower dose
is used for opioid-dependent individuals, who will show withdrawal
symptoms within minutes of being given the medication (129). For
any person who presents with significant respiratory depression,
the initial suggested dose is 2.0 mg i.v., regardless of the individual's
drug use history; a beneficial response should occur within 2 minutes.
Repeated doses can be administered every 3 minutes until respiratory
or CNS depression is completely reversed or until a maximum dose
of 10 mg i.v. has been given (128). If no response is observed after
administration of the 10 mg of naloxone, the diagnosis of opioid
overdose should be reconsidered. Because naloxone is rapidly absorbed
by the brain and then quickly redistributed and eliminated from
the body, its activity in the brain is short-lived (126, 130). Thus,
further monitoring and infusion of additional naloxone are needed
to continue antagonizing the effects of severe opioid overdose,
particularly if longer-acting opioids have been ingested (128, 131).
Monitoring for opioid withdrawal symptoms is also indicated because
patients may experience significant distress that can last for several
hours after reversal of an opioid overdose with an antagonist (129).
Acute sedative-hypnotic overdose is recognizable by slurred
speech, loss of coordination, and confusion and, in a severe overdose,
stupor, respiratory depression, and coma. Flumazenil is a potent
benzodiazepine-specific antagonist that competes at central synaptic GABA
receptor sites in a dose-dependent manner (132). In addition, it
may antagonize the sedative effects of other compounds that act
through GABA receptors, such as zolpidem, zaleplon, and eszopiclone
(133). However, it does not antagonize benzodiazepine effects at peripheral
GABAergic (e.g., renal, cardiac) receptor sites (134). Like naloxone,
flumazenil has poor bioavailability and a brief duration of activity
and is administered by repeated boluses or through continuous intravenous
infusion. Although it can be used as a low-dose (2 mg i.v.) diagnostic
probe for suspected benzodiazepine overdose or in the reversal of
benzodiazepines given for diagnostic or therapeutic procedures,
flumazenil must be carefully administered to benzodiazepine-dependent
patients and patients who have ingested mixed substances to avoid
the production of withdrawal seizures (135). Flumazenil can also
affect cerebral hemodynamics and is not recommended for situations
in which intracranial pressure may already be increased (e.g., in
the case of a head injury) (135). For these reasons, as well as
cost, flumazenil is not recommended for uncomplicated benzodiazepine
overdose that can be successfully managed by supportive ventilation
therapies.
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2. Medications to
treat withdrawal syndromes
Patients who develop tolerance to a particular substance also
develop cross-tolerance to other substances in the same pharmacological
class. Physicians can take advantage of cross-tolerance in the treatment
of withdrawal states by replacing the abused substance with a medication
that is in the same pharmacological class. Examples of this include
the use of methadone or buprenorphine in the treatment of opioid
withdrawal, benzodiazepines in the treatment of alcohol and sedative-hypnotic
withdrawal, and NRTs in the treatment of nicotine dependence (136–141).
Other medications are used to ameliorate indirect withdrawal-related
symptoms. For example, clonidine is an 
2-adrenergic
agonist that is useful in treating opioid withdrawal symptoms as
well as anxiety syndromes (129, 142). Nonspecific symptoms of withdrawal
such as headache and stomach upset may also require treatment using
medications such as acetaminophen and histamine2-receptor
antagonists, respectively.
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3. Agonist maintenance
therapies
Opioid agonist maintenance therapy may be the primary tool
available to engage an opioid-dependent individual in treatment
because it relieves unpleasant withdrawal syndromes and craving
associated with abstinence. The central and subjective effects of
agonist therapies render these agents more acceptable to opioid-dependent
patients than antagonist therapies, and adherence with treatment
with agonist therapies is greater than with antagonist therapies.
Opioid agonist maintenance therapies (described further below)
include methadone, a long-acting potent agonist at the mu opiate
receptor sites (126), and buprenorphine, a potent long-acting compound
that acts as a partial opioid agonist at mu receptor sites (126)
and that is prescribed alone or with naloxone (in a combination
tablet). An additional opioid agonist therapy, l--acetylmethadol (LAAM),
has an extended duration of action and high intrinsic activity at
the mu opiate receptor, but it has been withdrawn from the U.S.
market by its manufacturer because of the risk of cardiac arrhythmia.
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4. Antagonist therapies
Antagonist therapies are used to block or otherwise counteract
the physiological and/or subjective reinforcing effects
of substances. The narcotic antagonist naltrexone blocks the subjective
and physiological effects of subsequently administered opioid drugs
(e.g., heroin) (143, 144) without tolerance developing to its antagonist
effect (145) (see Sections VII.C.1.c and IX.E.1.b). Compared with
naloxone, naltrexone has good oral bioavailability (126) and a relatively
long half-life; it is also available in a long-acting injectable
preparation that may improve treatment adherence.
Mecamylamine, a nicotine antagonist, has also been studied,
but its effectiveness remains unclear (146, 147).
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5. Abstinence-promoting
and relapse prevention therapies
For promoting abstinence and preventing relapse in patients
with substance use disorders, certain medications may be useful.
Examples of such medications are disulfiram, naltrexone, and acamprosate
for alcohol use disorders and bupropion for nicotine dependence.
The ingestion of alcohol after disulfiram, an inhibitor of
the enzyme aldehyde dehydrogenase, has been taken results in the
accumulation of toxic levels of acetaldehyde accompanied by a host
of unpleasant, potentially dangerous but rarely lethal signs and
symptoms (148–151). The purpose of disulfiram is not to
make the patient ill but to prevent the patient from drinking impulsively
because he or she knows the symptoms that will result from drinking
while taking disulfiram (see Sections IV.C.3.b and IX.B.3.b).
Naltrexone, described above as an antagonist therapy for the
treatment of opiate dependence, is also effective in reducing alcohol
craving and preventing alcohol-induced relapse (152–154),
presumably because of the effect of mu opiate receptor antagonism
in blocking the centrally mediated reinforcing effects of alcohol
(155) (see Sections IV.C.3.a and IX.B.3.a).
Acamprosate (calcium bis-acetyl
homotaurine) is a small, flexible molecule that resembles GABA and
decreases glutamatergic neurotransmission, perhaps by acting as
an N-methyl-d-aspartate
antagonist (151, 156). It has been proposed that this medication
helps sustain abstinence in detoxified alcohol-dependent individuals
by reducing neuronal hyperexcitability during early recovery (156, 157) (see Sections IV.C.3.c and IX.B.3.c).
Treatment of nicotine dependence with the sustained-release
formulation of the antidepressant bupropion has been associated
with reductions in nicotine craving and smoking urges (158–160).
The mechanism of action for bupropion in the treatment of nicotine
dependence is unclear but is likely related to blockade of dopamine
and norepinephrine reuptake (161) as well as antagonism of high-affinity
nicotinic acetylcholine receptors (162) (see Sections III.E.2 and
IX.A.1.b).
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6. Medications to
treat co-occurring psychiatric conditions
The treatment of co-occurring psychiatric disorders may or
may not improve treatment outcome for the substance use disorder,
but if treatment of the co-occurring psychiatric disorder does not
occur, it is less likely that the treatment of substance use disorder
will be successful. The high prevalence of co-occurring psychiatric
disorders in substance-dependent patients implies that many such
patients will require specific pharmacotherapy for a co-occurring
disorder. Examples include the use of mood stabilizers for substance-dependent
patients with bipolar disorder, antipsychotics for patients with
psychotic disorders, and antidepressants for patients with major
depressive disorder (see also Section II.G.2.d).
Clinically significant issues for substance-dependent patients
receiving pharmacotherapy for co-occurring psychiatric disorders
include 1) synergy of prescribed medications and effects of the
abused substance (e.g., benzodiazepines and alcohol), 2) drug-drug
interactions that affect the efficacy of psychiatric treatment (e.g.,
antipsychotics and smoked tobacco), 3) nonadherence to treatment
because of intoxication and withdrawal states as well as drug-seeking
behaviors, and 4) intentional or unintentional overdose. Certain
medications used to treat co-occurring psychiatric disorders may
themselves be abused. For example, patients with a co-occurring
anxiety disorder may abuse benzodiazepines, patients with attention
deficit hyperactivity disorder (ADHD) may abuse prescribed stimulants,
and patients with a co-occurring psychotic disorder who are treated
with anticholinergics for antipsychotic adverse side effects may
abuse the anticholinergic adjunct. Substance-dependent patients
may also misuse prescribed medications in an attempt to ameliorate withdrawal
syndromes, enhance the effect of other substances of abuse, or accelerate
the action of the prescribed medication. Whenever possible, medications
with low abuse potential and relative safety in overdose should
be selected for the treatment of patients with a co-occurring substance
use disorder.
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F. Psychosocial Treatments
Some type of psychosocial intervention is usually available
in specialized substance use disorder treatment programs. These
approaches are the mainstay of treatment for users of certain classes
of substances (e.g., cocaine) for which there are no pharmacological
treatments with established efficacy. The major psychotherapeutic
treatments that have been studied in patients with substance use
disorders are cognitive-behavioral, behavioral, psychodynamic/interpersonal,
and recovery-oriented therapies. A growing body of efficacy data
from controlled clinical trials suggests that psychotherapy is superior
to control conditions as a treatment for patients with a substance
use disorder. However, no particular type of psychotherapy has been
found to be consistently superior when compared with other active
psychotherapies for treating substance use disorders. Even comparatively
brief psychotherapies appear to have durable effects among patients
with a substance use disorder (123).
After a discussion of the role of psychotherapy in substance
abuse treatment and the relation between psychotherapy and pharmacotherapy,
this section reviews the major psychosocial treatment approaches,
the principles underlying their use, and their application in the treatment
of patients with substance use disorders.
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1. Role of psychosocial
treatments
Psychosocial treatments for substance use disorders attempt
to counteract compulsive substance use by bringing about changes
in patients' behaviors, thought processes, affect regulation,
and social functioning. Although the techniques and theories of
therapeutic action vary widely across the different approaches reviewed
below, they all address one or more of a set of common tasks: 1)
enhancing motivation to stop or reduce substance use, 2) teaching
coping skills, 3) changing reinforcement contingencies, 4) fostering
management of painful affects, and 5) enhancing social supports
and interpersonal functioning (163). A central challenge for clinicians
treating individuals with substance use disorders is that the core
symptom, compulsive substance use, at least initially results in
euphoria or relief of dysphoria, with the aversive and painful effects
of substance use occurring some time after the rewarding effects.
This contrasts with the course of most other psychiatric disorders
(e.g., mood or anxiety disorders), in which the primary symptoms
are painful or aversive. In addition, substance use has come to
serve an important function in the individual's life by
the time treatment is sought. Sustained recovery from a substance
use disorder entails both relinquishing a valued element of life
and developing different behaviors, thought patterns, and relationships
that serve the functions previously met by substance use (164).
Psychosocial treatments are often essential for many aspects
of this recovery process: Sustained motivation is required to forgo
the rewards of substance use, tolerate the discomforts of early
and protracted withdrawal symptoms, and gather the energy to avoid
relapse despite episodes of craving that can occur throughout a
lifetime. Coping skills are required to manage and avoid situations
that place the individual at high risk for relapse. Alternative sources
of reward or symptom relief must be sought and used to fill the
place of substance use. Dysphoric affects, such as anger, sadness,
or anxiety, must be managed in ways that do not involve continued
substance use. Social relationships that are supportive of recovery need
to be developed or repaired.
Patients with substance use disorders vary widely in their
need for attention to each of these aspects of recovery, and brief
treatment or self-help methods may be sufficient for the recovery
of highly motivated patients with good interpersonal functioning
and social support. However, none of these processes can be assumed
to occur simply as a result of detoxification or with the administration
of medications. It is essential that these psychosocial aspects
of recovery be evaluated during treatment planning to determine
the need for behavioral treatments.
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2. Relation of psychosocial
treatments to pharmacotherapy for substance use disorders
Research has demonstrated that the utility of pharmacotherapies
for substance use disorders may be limited unless they are delivered
with adjunctive psychotherapy. For example, naltrexone maintenance
for opioid dependence is plagued by high rates of premature dropout
(165, 166) that can be lessened by concurrent behavioral or family
therapy (167). Without adjunctive psychotherapy, the utility of
disulfiram may be limited, in part because of low rates of medication
adherence (150); however, its effectiveness can be enhanced when
it is delivered in the context of a contract with a family member
or significant other (168). Methadone maintenance for opioid dependence
is the most successful pharmacological treatment of a substance
use disorder, with substantial evidence of its impact on treatment
retention and associated reductions in opioid use and illegal activity
(169). However, cross-program effectiveness varies widely in relation
to the quality and amount of ancillary psychosocial services delivered
(169). Moreover, McLellan et al. (170) have shown that methadone
maintenance alone yields acceptable results for only a small fraction
of patients and that outcome is enhanced in proportion to the intensity
of concomitant psychosocial services. More recently, a meta-analysis
confirmed that a combination of psychosocial treatment and methadone
maintenance produced greater reductions in heroin use by opioid-dependent
individuals than methadone maintenance alone (171). Similar results
have been found with nicotine replacement treatments: rates of sustained
abstinence are increased two- to fourfold when they are combined
with behavioral therapies (172, 173).
These findings suggest that even the most efficacious pharmacotherapies
for substance use disorders have limitations that need to be addressed
with psychosocial interventions. First, medications frequently affect
only part of the substance dependence syndrome while leaving other
aspects untouched. For example, methadone is highly effective in
relieving withdrawal symptoms and minimizing the impact of continued
opioid use, but by itself it has limited impact on counteracting
social impairments resulting from protracted substance use prior
to a patient's entering treatment (169). Also, most medications
have variable or partial effects on the target symptom. Second,
side effects or delayed effects of medications may limit acceptability
and adherence. Third, medications typically target only one class
of substances, whereas abuse of multiple substances is the norm
in treatment populations (174). Fourth, gains made while taking
the medication tend to diminish when the treatment is discontinued,
whereas vulnerability to relapse is lifelong. Psychosocial strategies
for countering these limitations and enhancing effectiveness of
pharmacotherapies include 1) increasing a patient's motivation
to stop substance use by taking the prescribed medication, 2) providing
guidance to the patient on using the medication and managing its
side effects, 3) maintaining the patient's motivation to
continue the medication after an initial period of abstinence is
achieved, 4) providing the patient with a supportive therapeutic
relationship aimed at preventing premature termination, and 5) helping
the patient develop skills to adjust to a life without substance
use.
The importance of psychosocial treatments is reinforced by
the recognition that there are only a handful of effective pharmacotherapies
for substance use disorders and that, for the most part, these therapies
are limited to the treatment of opioid, alcohol, and nicotine dependence
(175). Effective pharmacotherapies for dependence on cocaine and
other stimulants, marijuana, hallucinogens, and sedative-hypnotics
have yet to be developed. For individuals who abuse these latter
substances, psychosocial therapies remain the principal treatments.
Although the foregoing discussion has emphasized the need
for psychotherapy to enhance the effectiveness of pharmacotherapy,
this section would not be complete without considering the role
of pharmacotherapy in enhancing the efficacy of psychotherapy. These two
treatments have different mechanisms of action and targeted effects
that can counteract the weaknesses of either treatment alone. Psychotherapies
effect change by psychological means in the psychosocial aspects
of substance abuse, such as motivation, coping skills, dysfunctional
thoughts, or social relationships. The weaknesses of these treatments
include a limited effect on the physiological aspects of substance
abuse or withdrawal. Also, the impact of behavioral treatments tends
to be delayed, requiring practice, repeated sessions, and a "working
through" process. In contrast, the relative strength of
pharmacological treatments is their rapid action in reducing immediate
or protracted withdrawal symptoms, craving, and the rewarding effects
of continued substance use. In effect, pharmacotherapies for substance
use disorders reduce the patients' immediate access to
and preoccupation with the abused substance, freeing the patient
to address other concerns such as long-term goals or interpersonal
relationships. When medications are used in conjunction with psychotherapy,
the dropout rate from therapy is reduced because the patient's
urges to use and relapse to substance use are alleviated by the
effects of the medication. In addition, a longer duration of abstinence
can further enhance the efficacy of psychotherapy by preventing
substance-related effects on attention and mental acuity, thereby
maximizing the patient's ability for learning new behaviors
in therapy.
Because of the complementary actions of psychotherapies and
pharmacotherapies, combined treatment has a number of potential
advantages. As is reviewed later, research evidence on combined
treatment is sparse but generally supportive. Although factors such
as patient acceptance can limit the use of combined approaches,
it is important to note that for the treatment of substance use
disorders, no studies have shown that combined treatments are less
effective than either psychotherapy or pharmacotherapy alone.
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3. Cognitive-behavioral
therapies
CBTs for the treatment of substance use disorders are based
on social learning theories regarding the acquisition and maintenance
of the disorder (176). These therapies target two processes conceptualized
as underlying substance abuse: 1) dysfunctional thoughts, such as
the belief that the use of substances is completely uncontrollable,
and 2) maladaptive behaviors, such as acceptance of offers to use
drugs. Early versions of this approach (177, 178) were derived from
cognitive therapy for depression and anxiety by Beck and Emery (179)
and placed primary emphasis on identifying and modifying dysfunctional
thinking patterns. Other adaptations of this approach have broadened
the focus of therapy to help the patient master an individualized
set of coping strategies as an effective alternative to substance
use (176, 180). Typical cognitive strategies include fostering the
patient's resolve to stop using substances by exploring
positive and negative consequences of continued use, recognizing
seemingly irrelevant decisions that could culminate in high-risk
situations, and identifying and confronting thoughts about substance
use. Behavioral strategies are based on a functional analysis of
substance use (i.e, understanding substance use in relation to its antecedents
and consequences) and include the development of strategies for
coping with craving, preparing for emergencies, and coping with
relapse to substance use.
Social skills training, an element of CBT, recognizes that
alcohol and drug dependence commonly results in the interruption
of normal developmental acquisition of social skills as well as
the deterioration of previously learned social skills because of
the interference of drug-seeking and drug-using behaviors. Social
skills training targets an individual's capacity for 1)
effective and meaningful communication, 2) listening, 3) being able
to imagine someone else's feelings and thoughts to inform
one's own behavioral interactions, 4) being able to monitor
and modify one's own nonverbal communications, 5) being
able to adapt to circumstances to maintain relationships, and 6)
being assertive (181). This strategy has been successfully used
as an adjunct to a more comprehensive treatment plan and can be delivered
in a wide variety of outpatient treatment settings. It may be particularly
useful in certain dually diagnosed populations, such as patients
with schizophrenia (182) and adolescents at risk for beginning substance
abuse (183).
Relapse prevention is a treatment approach in which CBT techniques
are used to help patients develop greater self-control to avoid
relapse (184, 185). Specific relapse prevention strategies include
discussing the patient's ambivalence about the substance
use disorder, identifying emotional and environmental triggers of
craving and substance use, developing and reviewing specific coping
strategies to deal with internal or external stressors, exploring
the decision chain leading to reinitiation of substance use, learning
from brief episodes of relapse (slips) about triggers leading to
relapse, and developing effective techniques for early intervention
(184, 186). In more recent clinical trials (43, 187), techniques
drawn from cognitive therapy and relapse prevention have been combined
with the aims of initiating abstinence and preventing relapse.
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4. Motivational enhancement
therapy
MET is the longer-term follow-up to an initial brief intervention
strategy. It continues the use of motivational interviewing and
moves a patient closer to a readiness to change substance use behaviors
(reviewed in DiClemente et al. [6] and Miller
and Rollnick [49]). It combines techniques from
cognitive, client-centered, systems, and social-psychological persuasion
approaches and may be provided by trained clinicians in substance
abuse facilities, mental health clinics, and private practice offices.
MET is characterized by an empathic approach in which the therapist
helps to motivate the patient by asking about the pros and cons
of specific behaviors, exploring the patient's goals and
associated ambivalence about reaching those goals, and listening
reflectively to the patient's responses. This treatment
modality is effective even for patients who are not highly motivated
to change, which gives it a practical advantage over other therapies
for substance use disorders in many settings.
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5. Behavioral therapies
Behavioral therapies are based on basic principles of learning
theory (188), which deals with the role of externally applied positive
or negative contingencies on learning or unlearning of behaviors
that can range from simple autonomic reactions such as salivation
to complex behavioral routines such as purchasing drugs. When these
theories are applied to substance use disorders, the target behavior
is habitual excessive substance use, which is altered through systematic
environmental manipulations that vary widely depending on the specific
substance use behavior. These theories differ from those underlying
CBTs by not recognizing cognition as a domain independent of behavior.
The shared goals of behavioral therapies are to interrupt
the sequence of substance use in response to internal or external
cues and substitute behaviors that take the place of or are incompatible
with substance use. There are two broad classes of learning theory-based treatments:
1) those that are based on classical conditioning and focus more
on antecedent stimuli such as cue exposure therapy (189) and 2)
those that are based on operant conditioning and focus more on consequences
such as community reinforcement therapy (190). Representative behavioral
approaches are briefly described here.
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a) Contingency management
Contingency management therapy involves introducing rewards
for therapeutically desired behaviors (e.g., attending therapy sessions,
providing substance-negative urine samples) and/or aversive
consequences for undesirable behaviors (e.g., failure to adhere
to clinic rules) (191–193). As an adjunctive treatment,
contingency management has been used with a variety of substances
of abuse, including cocaine (193–196), opiates (197–200),
and marijuana (201). Incentives to be offered, behaviors to be reinforced,
and the reinforcement schedule vary widely by substance and also
depend on the role of contingency management within the larger treatment
plan (188). Although most studies have centered on abstinence from
substance use, contingency management procedures are potentially
applicable to a wide range of target behaviors and problems, including
treatment retention, adherence to treatment (e.g., retroviral therapies
for individuals with HIV), and reinforcement of other treatment
goals such as employment seeking (202) or work attendance (203). Contingency
management is effective when desired behaviors are rewarded with
vouchers that can be exchanged for mutually agreed-on items such
as movie tickets. Other reinforcers (e.g., free housing, direct
compensation) can be substituted for vouchers. The use of large
but low-probability reinforcers (e.g., earning the chance to draw
from a bowl and win prizes of varying magnitudes ranging from $1
to more than $100) is also effective (204, 205) and may
reduce the total costs of contingency management approaches (206).
Contingency contracting is a subtype of contingency management
based on the use of predetermined positive or negative consequences
to reward abstinence or punish, and thus deter, drug-related behaviors.
Negative consequences of substance use may include notification
of courts, employers, or family members. The effectiveness of this
approach depends heavily on the concurrent use of frequent, random,
supervised urine screening for substance use. When negative contingencies
are based on the anticipated response of others (e.g., spouses,
employers), the treating physician should obtain the patient's
written informed consent to contact these individuals at the time
the contract is initiated (207).
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b) Community reinforcement
The community reinforcement approach (CRA) is based on the
theory that environmental reinforcers for substance use perpetuate
substance use disorders and that, at the same time, patients with
substance use disorders lack positive environmental reinforcers
for sober activities and pleasures (208). CRA aims to provide individuals
with substance use disorders with natural alternative reinforcers
by rewarding their involvement in the family and social community;
thus, family members or peers play a role in reinforcing behaviors
that demonstrate or facilitate abstinence (190). In CRA, emphasis
is placed on improving environmental contingencies for activities
of a sober lifestyle to make that type of lifestyle preferable to
a substance-dependent lifestyle. In addition to individual behavioral
treatment and contingency management, the multifaceted CRA treatment
package typically includes conjoint marital therapy, training in
finding a job, counseling on substance-free social and recreational
activities, and a substance-free social club. CRA is often applied
with contingency management incentives (e.g., vouchers for recreation
or food) that are used to reward evidence of sober behavior (209, 210). CRA has been shown to be effective in treating alcohol dependence,
with adjunctive disulfiram treatment increasing its effectiveness
(211). CRA can be clinic or office based, but it is largely practiced
in residential or partial hospitalization programs, therapeutic
communities, and community residential facilities.
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c) Cue exposure and
relaxation training
Cue exposure treatment involves exposing a patient to cues
that induce craving while preventing actual substance use and, therefore,
the experience of substance-related reinforcement (212). Cue exposure
can also be paired with relaxation techniques and drug-refusal training
to facilitate the extinction of classically conditioned craving
(213, 214). As an alternative, relaxation training has been used
alone to provide a nonsubstance response to counteract dysphoric
affects or anxiety.
Aversion therapy involves coupling substance use with an unpleasant
experience such as mild electric shock, pharmacologically induced
vomiting, or exaggerated effects of the substance. This treatment
seeks to eliminate substance use behaviors by pairing them with punishment.
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6. Psychodynamic
and interpersonal therapies
Psychodynamic psychotherapies vary but generally attribute
symptom formation and personality characteristics to traumas and
deficits during an individual's development that result
in unconscious psychological conflict, faulty learning, and distortions
of intrapsychic structures as well as internal object relations
(215) and that have a profound effect on interpersonal relationships.
These developmental events and their sequelae are inextricably interconnected
to the individual's underlying neurobiology (as determined
by genetic and other influences), which can in turn be altered by
life experience, including learning, psychological events, and psychotherapy
(216). Systematic testing of the efficacy of psychodynamic treatments
for substance use disorders has occurred only with supportive-expressive
therapy (217), a comparatively brief psychodynamically oriented
treatment based on the use of interpretation and a supportive therapeutic
relationship to modify negative views of the self and others. Two
trials have supported the efficacy of supportive-expressive therapy
for methadone-maintained, opioid-dependent patients (177, 218). However,
an additional randomized trial found that combined individual and
group drug counseling was superior to a combination of individual
support-expressive therapy and group drug counseling in treating
patients with cocaine dependence (219).
IPT for substance use disorders is based on the concept that
dysfunctional social relationships either cause or prevent recovery
from a substance use disorder (220). By discovering the relation
between interpersonal problems and substance use, the patient can
move toward making changes aimed at building a social network that
is supportive of recovery. Clinical study of IPT for substance use
disorders has been limited.
Group therapy is viewed as an integral and valuable part of
the treatment regimen for many patients with a substance use disorder.
Many different types of therapies have been used in a group format
with this population, including CBT, IPT, and behavioral marital, modified
psychodynamic, interactive, rational emotive, Gestalt, and psychodrama
therapies (221–225).
Group therapies permit efficient use of therapist time (226).
In addition, aspects of group therapy may make this modality more
effective than individual treatment for individuals with a substance
use disorder. For example, given the social stigma attached to having
lost control of substance use, the presence of other group members
who acknowledge having a similar problem can provide comfort. In
addition, other group members who are further along in their recovery
can act as models, illustrating that attempts to stop substance
use are not futile. These more experienced group members can offer
a wide variety of coping strategies that go beyond the repertoire
known even by the most skilled individual therapist. Furthermore,
group members frequently can act as "buddies" who
offer continued support outside of group sessions in a way that
most professional therapists do not.
Finally, the public nature of group therapy provides a powerful
incentive to individuals to avoid relapse. The ability to publicly
declare the number of days sober coupled with the fear of having
to publicly admit to relapse is a strong force that helps group
members fight a disorder that is characterized by a breakdown of
internalized control mechanisms. Individuals with substance use
disorders have been characterized as having poorly functioning internal
self-control mechanisms (227, 228), and the group process can provide
a robust source of external control. Moreover, because the group
is composed of individuals recovering from substance use disorders,
members may be better at detecting each other's concealed
substance use or early relapse signals than would an individual
therapist who may not have personal experience with a substance
use disorder.
Although clinical trials of group therapy for substance use
disorders are comparatively rare, the available data suggest that
the efficacy of group treatment is comparable with that of individual
therapies (229, 230). No compelling empirical evidence is available
to document the advantages or disadvantages of choosing group or
individual treatment for substance use disorders. Because many patients
have experience with group or individual therapy, patient preferences
should be considered when choosing between the two types of treatment
delivery or when developing a combined treatment program.
Dysfunctional families, characterized by impaired communication
among family members and an inability of family members to set appropriate
limits or maintain standards of behavior, are associated with poor
short- and long-term treatment outcome for patients with substance
use disorders (231). Family therapy may be delivered in a formal,
ongoing therapeutic relationship or through periodic contact. Goals
of family therapy include obtaining information about the patient's
current attitudes toward substance use, treatment adherence, social
and vocational adjustment, level of contact with substance-using
peers, and degree of abstinence, as well as encouraging family support
for abstinence, maintaining marital and family relationships, and
improving treatment adherence and long-term outcome (232–235).
They may also include behavioral contracting to maintain treatment
(e.g., contracting with a partner for disulfiram treatment) or increasing
positive incentives associated with sober family activities. Even
the brief involvement of family members in the treatment program
can enhance treatment engagement and retention.
Controlled studies have shown positive outcomes of involving
non-alcohol-abusing family members in the treatment of an alcohol-abusing
individual (236). More recent studies have demonstrated the effectiveness
of family involvement in substance use disorder treatment for both
women and men (237, 238), including patients on methadone maintenance
(170). Family therapy, often in combination with other approaches,
has also been studied extensively and has shown good evidence for
efficacy in adolescents (239–242).
Different theoretical orientations of family therapy include
structural, strategic, psychodynamic, systems, and behavioral approaches.
Family interventions include those focused on the nuclear family;
on the patient and his or her spouse or partner; on concurrent treatment
for patients, spouses or partners, and siblings; on multifamily
groups; and on social networks (120, 243, 244). Of the many types
of family therapy used to treat substance use disorders, the preponderance
of clinical trial evidence has been obtained for the behavioral and
strategic approaches (245). The support for behavioral couples treatment
is particularly strong (246).
Family intervention is indicated in circumstances in which
a patient's abstinence upsets a previously well-established
but maladaptive style of family interaction (233, 247) and in which
other family members need help adjusting to a new set of individual
and family goals, attitudes, and behaviors. Family therapy that
addresses interpersonal and family interactions leading to conflict
or enabling behaviors can reduce the risk of relapse for patients
with high levels of family involvement. A major role for family
and couples intervention is to enlist concerned significant others
to foster treatment seeking and retention in family members who
are unmotivated to change substance abuse behaviors. As reviewed
by Miller et al. (248), most attention has been paid to behavioral
coping strategies, 12-step approaches, and confrontational interventions
(249), all of which are associated with high rates of treatment
entry for patients who receive the intervention. However, in helping
family members engage their significant others in treatment, concerned
significant others and identified patients are more likely to follow
through and show better results with less confrontational approaches,
including CRA and community reinforcement and family training (250),
than with more traditional interventions (248). Couples and family
therapy are also useful for promoting psychological differentiation
of family members, providing a forum for the exchange of information
and ideas about the treatment plan, developing behavioral management
contracts and ground rules for continued family support, and reinforcing
behaviors that help prevent relapse and enhance the prospects for
recovery. There is also some evidence that these approaches can
improve the psychosocial functioning and decrease the likelihood
of substance use in children living with a parent abusing alcohol
or other substances (251, 252).
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9. Self-help groups
and 12-step-oriented approaches
The most widely available self-help groups (also called mutual
help groups) are based on the 12-step approach,
originally embodied in AA (253, 254), which emphasizes the concept
of substance dependence as an incurable, progressive disease that
has physical, emotional, and spiritual components. The 12-step programs
firmly endorse the need for abstinence and consider themselves lifelong
programs of recovery, even though initial success is attained one
day at a time. The importance of recognizing and relying on a "higher
power" or a power greater than the individual is a central
element of these programs. Also key are the 12 steps of recovery,
which focus first on surrender and acceptance of one's
disease, second on a personal inventory, third on making amends
and personal change, and finally on bringing the message to others.
In addition, 12-step groups help members with relapse prevention
by providing role models, social support, social strategies for
maintaining a sober lifestyle, and opportunities for structured
and unstructured substance-free social events and interactions.
Members of self-help groups can attend meetings on a self-determined
or prescribed schedule, which, if necessary, could be every day
or even more than once a day. Periods associated with high risk
for relapse (e.g., weekends, holidays, evenings) are particularly
appropriate for attendance. A sponsor who is compatible with the
patient can provide important guidance and support during the recovery
process, particularly when the patient is facing periods of emotional
distress and increased craving. The straightforward advice and encouragement
about avoiding relapse from a recovering sponsor as well as his
or her personalized support are important features of 12-step groups.
For clinicians who are treating patients who report involvement
in self-help groups, it is useful to ask if they are attending meetings,
if they have obtained a sponsor, and if they are attending other
activities associated with the self-help group (e.g., self-help group–sponsored
social gatherings, retreats).
Another significant advantage to 12-step groups is their broad
availability. AA is a worldwide organization with an estimated 2.2
million members in 150 countries (255), and 12-step groups have
expanded to include treatment of nearly every type of substance
use (Cocaine Anonymous, Marijuana Anonymous, Methadone Anonymous,
Narcotics Anonymous, Nicotine Anonymous, "Crystal Meth" Anonymous).
Self-help groups based on the 12-step model are also available for
family members and friends (e.g., Al-Anon, Alateen, Nar-Anon) and
provide group support and education about the disorder, with the
goal of reducing maladaptive enabling behavior in family and friends.
In general, active participation in self-help groups has been
correlated with better outcomes (256). AA has been effective for
both men and women and appears to be particularly useful for those
with more severe alcohol dependence (257–259). Other recent
research has suggested that 12-step groups may also benefit patients
dependent on substances such as cocaine (256). For patients concurrently
receiving professional substance abuse treatment, there is growing
empirical evidence that improved treatment outcomes are associated
with participation in self-help groups (260–266). Furthermore,
several studies (43, 219, 265, 267) support the efficacy of professional
treatment, including TSF therapy (268) and individual drug counseling
(269), that enhances a patient's motivation to participate
in 12-step programs. These findings have important clinical implications,
given that these approaches are similar to the dominant model applied
in most community treatment programs (270). Thus, for many patients,
even those who may still be actively using substances, referral
to a 12-step program can be helpful at all stages in the treatment
process.
An individual's refusal to participate in a self-help
group is not synonymous with his or her resistance to treatment
in general. Despite their many potential benefits, self-help groups
are not useful for all patients. Some individuals' apparent
resistance to self-help group participation can be addressed by
individualizing the choice of a group to the patient's
needs. For example, young people generally do better in groups that
include age-appropriate peers in addition to some older recovering
members. Patients who require psychotropic medications for co-occurring
psychiatric disorders should be directed to groups in which this
activity is recognized and supported as useful treatment rather
than as another form of substance abuse. The spiritual tenets of
traditional 12-step programs can be a deterrent to participation
for individuals who do not embrace these ideas. Although not widely
available, alternative self-help groups such as Women for Sobriety
(271), Secular Organizations for Sobriety (272), and Self-Management
and Recovery Training (273) have been developed to address this
problem and may be an option for some patients.
The efficacy of brief interventions has been studied mostly
in connection with alcohol use disorders. The interventions were
initially designed to facilitate the treatment of alcohol abuse
or dependence in a setting other than a substance abuse treatment
facility (e.g., primary care clinic, mental health clinic, EAP)
(274, 275). More recent evidence suggests that brief interventions
are also effective with other substance use disorders, including
cannabis (276), opioid (277), and nicotine (278) dependence and
in special populations such as adolescents (279), patients with
co-occurring psychiatric and substance use disorders (280), and
patients in the military (281).
The A-FRAMES model is the core structure of a brief intervention: Assessment,
providing objective Feedback, emphasizing
that Responsibility for change belongs
to the patient, giving clear Advice
about the benefits of change, providing a Menu
of options for treatment to facilitate change, using Empathic
listening, and emphasizing and encouraging Self-efficacy
with the patient (49). Despite the short time required to implement
a brief intervention, treatment facilities that do not specialize
in substance abuse treatment often experience difficulties in using
this strategy, including inadequate time available during face-to-face
encounters and clinicians' negative attitudes toward substance
use (282, 283).
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11. Self-guided therapies
Self-help therapies guided by written, programmed, or Internet-based
instruction have been shown to be effective for heavy users of legal
substances (i.e., alcohol, nicotine) who do not meet criteria for
a substance use disorder. The target population for such approaches typically
includes students or general medical patients rather than individuals
who are seeking treatment for a substance use disorder.
Self-help manuals and behavioral self-control training teach
patients how to 1) set goals for substance reduction or cessation,
2) monitor progress toward achievement of these goals, 3) reward
oneself for progress, 4) learn new coping skills that will facilitate
substance reduction or abstinence, and 5) perform functional analysis
of behaviors associated with substance use (284). These therapies
are available as manual-guided self-help programs, manual-guided
therapies with a clinician, and computer-guided programs (285, 286).
They are therefore available for home use as well as office- and
clinic-based use.
Although these approaches are sometimes helpful for those
at high risk for developing a substance use disorder or substance-related
medical consequences, such minimal therapies may not be sufficient
for treatment-seeking patients who already have a substance use disorder.
The use of hypnotherapy for substance use disorders has been
most studied as an aid in the cessation of cigarette smoking, with
its usual goal being to implant unconscious suggestions that will
deter use of a substance, such as "smoking will be unpleasant." Despite the
widespread use of hypnosis in this context, there is little scientific
validation to support its effectiveness in the treatment of nicotine
dependence (287).
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G. Clinical Features
Influencing Treatment
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1. Use of multiple
substances
Many patients entering treatment for a specific substance
use disorder abuse more than one substance, and co-occurring nicotine
dependence is particularly common. For some patients, there is a "drug
of choice," with other substances serving as a substitute
when the primary substance is unavailable. Others routinely use
multiple substances simultaneously. An individual's concurrent
use of two or more substances may be motivated by his or her wish
to modify the effects of the primary drug of choice or to prevent
or relieve withdrawal symptoms. In addition, many patients use multiple
substances because of their availability. Frequent drug combinations
include 1) cocaine and alcohol; 2) cocaine and heroin; 3) heroin
and benzodiazepines; 4) alcohol, cocaine, and benzodiazepines; 5)
nicotine and any other drug; 6) multiple "club drugs" (e.g.,
3,4-methylenedioxymethamphetamine [MDMA], -hydroxybutyrate [GHB],
ketamine); 7) "club drugs" with prescription medications (e.g.,
MDMA with sildenafil and/or fluoxetine); and 8) opioids,
stimulants, sedatives, steroids, and other substances. The severity
of abuse of each substance and the motivation to stop using each
substance may vary widely in individuals who abuse multiple substances.
The treatment of patients using multiple substances may be
complicated by 1) simultaneous intoxication or withdrawal from two
or more drugs, 2) varying time frames for experiencing withdrawal
symptoms, 3) the need to detoxify the patient from more than one drug,
and 4) potential interactions between an abused substance and medications
used to treat a comorbid substance use disorder (e.g., inadvertent
precipitation of opioid withdrawal in patients treated with naltrexone
for alcohol dependence).
Although the presence of multiple substance use disorders
is the norm, there is limited research to guide clinicians on adapting
the usual evidence-based clinical interventions to the treatment
of individuals using more than one substance, including medication
and psychosocial treatments. The best recommendation is for the
clinician to do a comprehensive assessment of the patient and integrate
the evidence-based treatment approaches, including pharmacological
and psychosocial treatments, for each specific substance use disorder (288).
The presence of a substance use disorder will have an impact
on psychiatric issues, such as the risk of suicide or other self-injurious
behaviors and the risk of aggressive behaviors, including homicide.
In addition, the presence of co-occurring psychiatric symptoms or
disorders affects the patient's treatment adherence as
well as the onset, course, and prognosis of the substance use disorder
(170, 288–292). These factors need to be taken into consideration
when arriving at a treatment plan for an individual patient.
The frequency of suicide attempts and death by suicide is
substantially higher among patients with a substance use disorder
than in the general population. A systematic review of retrospective
and prospective cohort studies of substance use disorders and suicide
(293) demonstrated that individuals with alcohol use disorder, opioid
dependence, or mixed drug use have a substantially greater likelihood
of suicide compared with the general population, with a 9.8-, 13.5-,
and 16.9-fold elevated risk, respectively. This review reported
insufficient evidence to compare the suicide risk among patients
with other drug use disorders (e.g., cocaine dependence). In terms
of lifetime suicide mortality, a review of 83 studies demonstrated
a lifetime suicide risk of 7% in individuals with an alcohol
use disorder, which is comparable to that of individuals with a
mood disorder (6%) or schizophrenia (4%) (294).
These rates vary by country and may be slightly lower in the United
States (295). In addition, significant rates of substance use disorders
are found in psychological autopsy studies of individuals who have
died by suicide (296–300), with a recent or impending interpersonal
loss being a frequent apparent precipitant (301).
Rates of suicidal ideation and suicidal behaviors, including
suicide attempts, are also increased in individuals with a substance
use disorder. For example, in a recent prospective study, treatment-seeking
individuals with alcohol dependence were found to have attempted
suicide seven times more frequently than age-matched, non-alcohol-dependent
comparison subjects during the 5-year follow-up period after the
initial evaluation (302). The alcohol-dependent individuals who
attempted suicide (4.5%) were more likely than the other
individuals to have made prior attempts; other related factors were
earlier onset of the substance disorder, more severe substance dependence,
dependence on multiple substances, more panic symptoms, being separated
or divorced, having had prior treatment, and having been diagnosed
with a substance-induced psychiatric disorder (302). In addition, significant
high rates of substance use disorders are seen among individuals
who have attempted suicide (296, 303–305).
The risk of suicidal behaviors and death by suicide is further
increased for individuals with a substance use disorder in the context
of certain co-occurring psychiatric disorders, such as major depressive
disorder, bipolar disorder, and cluster B personality disorders.
The presence of major depressive disorder substantially increases
impulsive suicidal behaviors and suicide risk (298, 303, 306–308).
A recent review of the literature on co-occurring alcohol use disorders
and major depressive disorder demonstrated that this comorbidity
increases the risk of suicidal ideation, suicidal behaviors, and
death by suicide (309). Among patients diagnosed with major depressive
disorder and bipolar disorder, cigarette smoking has also been found
to be an independent predictor of future suicidal behavior (310).
Prospective studies of patients with co-occurring bipolar
and substance use disorders consistently report greater frequency
of lifetime suicide attempts and suicidal ideation compared with
bipolar disorder patients with no co-occurring substance use disorder
(311–313). Bipolar patients with co-occurring anxiety symptoms
or cluster B personality disorder features and a substance use disorder
may be at the greatest risk for suicidal behaviors (314, 315).
Patients with co-occurring cluster B personality and substance
use disorders also have a greater risk of suicidal ideation and
death by suicide (316, 317). This population is also at greater
risk for accidental death by injection drug overdose (318).
Despite this clear evidence for an increased risk of suicidal
behaviors in individuals with a substance use disorder, few controlled
studies are available to assist in guiding the treatment of such
patients (319). As in the care of any patient with a psychiatric
disorder, suicide risk should be assessed regularly and in a systematic
manner. Assessment of suicide risk includes determining the presence
or absence of current suicidal thoughts, intent, and plan; a history
of suicide attempts (e.g., lethality of method, circumstances);
a family history of suicide; a history of aggression (e.g., weapon
use, circumstances); the intensity of current depressive and other
mood symptoms; the current treatment regimen and response; recent life
stressors (e.g., marital separation, job loss); substance use patterns;
psychotic symptoms; and current living situation (e.g., social supports,
availability of weapon). In substance-using individuals, suicidal
ideation and suicide attempts may occur in the context of a major
depressive episode or result from substance-induced sadness or dysphoria
combined with increased impulsivity and poor judgment. However,
individuals with a substance use disorder can also be at risk for
suicide even in the apparent absence of depression. In terms of
treatment implications, care should be used when prescribing potentially
toxic medications to a suicidal patient. For additional recommendations
on the assessment and treatment of suicidal patients with substance
use disorders, the reader is referred to APA's Practice
Guideline for the Assessment and Treatment of Patients With Suicidal
Behaviors (301).
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b) Risk of aggressive
behaviors, including homicide
Substance use disorders are associated with an increased risk
for aggressive behaviors toward others, including physical assault,
sexual aggression, domestic violence, child abuse, and homicide
(320–322). Substance intoxication and withdrawal states
may be associated with anxiety, irritability, agitation, impaired
impulse control, disinhibition, decreased pain sensitivity, and
impaired reality testing; these effects are hypothesized to account
for the increased aggressive behaviors associated with substance
use. In particular, intoxication with substances such as alcohol,
cocaine, methamphetamine, PCP, anabolic steroids, and hallucinogens
may be associated with aggression (138, 323–327), whereas withdrawal
from substances such as alcohol, opioids, sedative-hypnotics, and
cannabis can lead to withdrawal syndromes associated with a risk
of aggressive behaviors (138, 320, 328). Intoxication with marijuana
or hallucinogens may inadvertently lead individuals to perform aggressive
acts because of a faulty perception of reality coupled with high
levels of anxiety and paranoia (329–331). Substance use
disorders are also indirectly associated with aggressive behaviors
engaged in to obtain illicit or expensive substances. Although it is
important to assess for and be aware of the potential for aggressive
behaviors in individuals with a substance use disorder, it is also
important to assess for substance use disorders in all individuals
who present with a history of agitation or aggression. Because family
and partners may be affected by substance-related domestic violence,
systematic screening and referral for domestic violence treatment
interventions may effectively reduce domestic violence. Some treatments
such as abstinent partner therapy (e.g., coping skills training [332])
and couples therapy (e.g., behavioral couples therapy [333])
have been shown to reduce alcohol-related domestic violence in randomized,
controlled trials.
Individuals with substance use disorders frequently report
sleep disturbances, particularly after being detoxified. For some
patients, managing sleep disturbances will be an important component
of the treatment plan. Indeed, some studies have demonstrated that among
detoxified alcohol-dependent individuals, insomnia is a strong predictor
of relapse (334–336). Despite the recognition that sleep
disturbances are a problem among individuals with substance use
disorders, only a handful of studies have examined the treatment
of sleep disturbances in these individuals, and these studies have
focused only on individuals with alcohol dependence. For example,
one small double-blind study found that trazodone was superior to
placebo in improving sleep in alcohol-dependent individuals with
insomnia (337). In an open-label study comparing trazodone and gabapentin
for the treatment of insomnia in alcohol-dependent individuals,
both medications were found to improve insomnia, but the gabapentin
group showed greater improvements than the trazodone group (338).
Given the open-label nature of this study, more research is needed
to determine if gabapentin is an effective treatment for sleep disturbances
related to alcohol dependence. In addition, more research is needed
to determine if trazodone and gabapentin, as well as other sedating
psychotropic medications, can effectively treat sleep disturbances
not only in individuals with alcohol dependence but also in those
with other substance use disorders.
In addition to the studies of pharmacological agents, there
has been one randomized, controlled study that showed that CBT strategies
helped improve sleep disturbances in alcohol-dependent individuals
in recovery (339). As with the pharmacological treatments for sleep
disturbances, more research is needed to determine if these strategies
will help improve insomnia in individuals with other substance use
disorders as well.
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d) Co-occurring psychiatric
and substance use disorders
Co-occurring psychiatric and substance use disorders are common
in all treatment settings (e.g., centers for the treatment of substance
use disorders, mental health clinics, primary care settings, emergency
departments) and in the general community. In fact, only a few differences
(e.g., higher prevalence of schizophrenia and primary psychotic
disorders in mental health care settings, more severe patterns of
substance use in substance use treatment settings) are observable
between patients with co-occurring psychiatric disorders receiving
treatment in substance abuse treatment centers and patients with
co-occurring substance use disorders receiving treatment in mental
health treatment centers (340). In community population samples
studied in the National Comorbidity Survey (341), individuals with
alcohol dependence had high rates of clinically significant depression
during their lifetime (men: 24% depression and 11% dysthymia;
women: 49% depression and 21% dysthymia). Individuals
with bipolar disorder had high rates of alcohol (61%) and
other substance (41%) dependence (342). Treatment-seeking
individuals have even higher rates of co-occurring disorders (343–345).
For example, Penick et al. (346) studied a U.S. Department of Veterans
Affairs (VA) hospital outpatient population with alcohol dependence
or abuse and found that 56% reported co-occurring psychiatric
disorders. In substance use disorder treatment settings, depression,
anxiety, and personality disorders frequently occur. However, posttraumatic
stress disorder (PTSD), adult ADHD, learning disabilities, social anxiety
disorder, eating disorders, and pathological gambling are also common
and are often underrecognized and undertreated (121, 288).
Individuals with nicotine dependence are more likely to have
co-occurring psychiatric disorders than the general U.S. population
(347). Furthermore, in mental health and substance use disorder
treatment settings, nicotine dependence continues to be the most
common co-occurring substance use disorder, with approximately 60%–95% of
patients being nicotine dependent, although this varies by the type
of psychiatric disorder and the treatment setting (348). One analysis
of nicotine use as reported in the National Comorbidity Survey found
that individuals with psychiatric disorders were about twice as
likely to smoke as the general population and that about 44% of
the cigarettes smoked in the United States were smoked by individuals
with a psychiatric disorder (349).
Use of multiple substances and co-occurring psychiatric and
substance use disorders are now so common in treatment settings
that these combinations should be expected. Thus, all patients with
a substance use disorder should be carefully assessed for the presence
of co-occurring psychiatric disorders, including additional substance
use disorders. Conversely, patients with identified psychiatric
disorders should be routinely assessed for the presence of a co-occurring
substance use disorder (350, 351).
Treating individuals with co-occurring psychiatric and substance
use disorders in traditional inpatient and outpatient programs is
challenging. Patients' motivation to change may vary according
to the type of substance(s) they use and the severity of their psychiatric
issues, and this needs to be taken into consideration in treatment
planning. Recent research and consensus opinions by experts in the
field support the notion that the integration of substance abuse
and mental health treatment strategies, including integrated systems,
programs, and clinical treatment, improves patient outcome (80, 121, 352, 353). There is growing evidence that patients in psychiatric
or substance abuse treatment settings have better outcomes if they
receive integrated treatment for their coexisting psychiatric and substance
use disorders (121, 288, 354–356). Integrated treatment
usually requires incorporating and modifying traditional psychiatric
and substance abuse treatment methods so that the co-occurring disorders
receive simultaneous treatment.
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a. Integrated treatment
Recent research and clinical experience (80, 288) has also
shed light on the question of treatment timing (e.g., if co-occurring
disorders should be treated together in an integrated manner or
in what circumstances one problem should be addressed before another).
In general, the length of the observation period for a psychiatric
or substance use disorder will be determined by balancing the following
considerations: the degree of diagnostic certainty, the severity
of the patient's condition, and the anticipated benefits
and risks of the proposed treatment (288, 353).
The integrated treatment of co-occurring psychiatric and substance
use disorders can include psychosocial and/or pharmacological
interventions. Initial treatment efforts should include engaging
the patient in treatment and assessing and managing the most severe symptoms
of both types of disorders. This may include addressing symptoms
of intoxication or withdrawal. Sometimes severe psychiatric symptoms
(e.g., psychosis, suicidal ideation) can be managed while a patient
is intoxicated or experiencing withdrawal; such patients may require
immediate treatment in an emergency department or an inpatient psychiatric
unit. Once a patient's acute psychiatric symptoms and intoxication
or withdrawal states have been stabilized, the patient can be evaluated
for treatment in an ongoing rehabilitative treatment program. When
patients are being treated in a substance abuse treatment setting,
their psychiatric symptoms should be monitored and addressed clinically through
psychiatric medications, when appropriate, as well as through integrated
psychosocial strategies (e.g., teaching patients mood management
as part of relapse prevention therapy) and integrated treatment
approaches for psychiatric disorders and substance use disorders
(357).
In a psychiatric treatment setting, it would be incorrect
to assume that successful treatment of a psychiatric disorder will
resolve the substance use disorder. The substance use disorder will
require specific treatment even when it arises in the context of
another psychiatric disorder, a situation that is quite common and
that presents an opportunity for the prevention of a secondary disorder
(358).
Certain psychosocial and pharmacological treatments have been
studied for specific combinations of psychiatric and substance use
disorders (e.g., major depression and alcohol dependence, schizophrenia
and cocaine dependence) (288, 353); the literature about these treatments
is presented in the specific substance use disorder sections of
this practice guideline. The reader is also advised to review other
APA practice guidelines for the treatment of patients with specific
psychiatric disorders for additional information.
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b. Pharmacological management of psychiatric disorders
In most patients, the same medications are recommended for
the treatment of a specific psychiatric disorder whether that disorder
co-occurs with a substance use disorder or not. Clinical issues
such as medication tolerability, safety, and abuse potential are
important considerations in choosing a medication and will influence
traditional psychopharmacological treatment algorithms. There is
no evidence to suggest that the duration of pharmacotherapy for
a psychiatric disorder in conjunction with a co-occurring substance
use disorder would differ from that needed to treat the psychiatric
condition alone, and there are no data to suggest that decisions
about continuation and maintenance treatment should differ (288). An
important clinical question in treating a co-occurring psychiatric
disorder in a substance use disorder treatment setting is whether
the prescribing clinician should initiate psychiatric medications
during the acute treatment of the substance use disorder. For some
psychiatric disorders (especially depression, generalized anxiety
disorder [GAD], social anxiety disorder, and PTSD),
there have been widely differing opinions about the amount of time
a patient should be abstinent from a substance before a definitive
diagnosis of a co-occurring psychiatric disorder versus a substance-induced
psychiatric disorder can be made. If there is little overlap between
the symptoms observed and the expected abstinence syndrome (such
as bulimia nervosa in an opioid-dependent patient), then the psychiatric
diagnosis can be immediately established. In circumstances when
prominent mood or anxiety symptoms could be equally attributable
to early abstinence or an independent co-occurring psychiatric disorder,
a clinician may consider whether similar symptoms occurred before
the substance use or during previous abstinence periods or whether
the individual's family history suggests a vulnerability
to a co-occurring mood or anxiety disorder. A common recommendation
is to consider the severity of an individual's functional
impairment when deciding whether or not to initiate pharmacotherapy,
continue ongoing monitoring of symptoms, and initiate psychosocial
treatment strategies for the management of anxiety and depression (288).
Medication nonadherence is common among individuals with co-occurring
psychiatric and substance use disorders (359, 360). Nonadherence
can be due to many factors, including cognitive impairment, the
patient's fear of the interaction between prescribed medication
and substances being abused, fear that the prescribed medication
is itself harmful, change in motivation, and lack of support. Some
patients attending 12-step meetings may feel pressure from some
group members not to take psychiatric medications because they are "mood
altering"; however, AA does support the appropriate use
of needed medications (361, 362). AA brochures and other resources
do state a reasonable concern about individuals' avoiding
psychotropic medications with an abuse potential (e.g., sedative-hypnotics, anxiolytics,
stimulants). When such medications are necessary, a clinician should
prescribe them with caution and closely monitor their use (e.g.,
dispense in limited quantities, track prescription refills, monitor
ongoing medical necessity for and the patient's response
to the medication).
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c. Medications to treat substance use disorders
Medications for treating substance use disorders, such as
those for managing acute withdrawal and protracted withdrawal symptoms
or reducing craving, have not been well studied in dually diagnosed
populations but should be considered for these patients. The presence
of a co-occurring mental illness may influence a clinician's
decision to prescribe disulfiram for alcohol-dependent patients
if, for example, the clinician is concerned about a patient's
capacity to adhere to prescribing instructions due to acute psychiatric
symptoms. However, a 12-week multicenter, randomized, controlled
trial of disulfiram in patients with co-occurring alcohol dependence
and psychiatric illness demonstrated the safety and effectiveness
of this medication with this population (363). This same study also
substantiated the safety and efficacy of naltrexone use in this
population. However, no further benefit was achieved in this study
by combining disulfiram and naltrexone.
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d. Integrated psychosocial treatments
Psychosocial treatment is very important in the treatment
of a substance use disorder both with and without a co-occurring
psychiatric disorder. Integrated psychotherapy approaches represent
some of the most recent advances in psychosocial treatments, and
several have been developed for specific subtypes of co-occurring
disorders. A common feature of these integrated therapies is their
blending of traditional evidence-based psychotherapies with traditional
evidence-based substance use disorder therapies such as MET, relapse
prevention therapy/CBT, and TSF therapy. Examples of psychiatric
disorders for which integrated treatments have been developed include
PTSD (364–368), bipolar disorder (369), schizophrenia (80, 360, 370–372), and personality disorders (373, 374). The
efficacy of these integrated psychotherapies is being actively investigated
in individual as well as in family and group modalities (375–377).
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(2) Treatment in the presence of specific co-occurring
psychiatric disorders
A review of the literature examining nicotine dependence among
individuals with schizophrenia demonstrated prevalence rates of
68%–88% among outpatients and 81%–88% among
inpatients (378), suggesting that substance use vulnerability alone
cannot account for the high smoking rates among patients with schizophrenia.
Patterns of nicotine use among patients with schizophrenia are more
severe than in patients with other psychiatric diagnoses (379),
and these usage patterns are associated with increased morbidity
and mortality due to tobacco-related medical diseases such as cancer
and cardiovascular and respiratory diseases (359, 380–383).
Apart from nicotine dependence, about 40%–60% of individuals
with schizophrenia will have another co-occurring substance use
disorder during their lifetime (353, 384, 385). Substance-abusing
individuals with schizophrenia are more likely to be male, young,
and less educated and have better social skills than those not abusing
substances, but they have less peer support and poorer treatment
outcomes in traditional substance abuse treatment settings because
of the stress associated with the confrontational treatment approaches
sometimes used in these programs (353, 386). Because substance abuse
treatment staff typically have limited training in managing psychosis
and because mental health clinicians are trained and able to provide
both medications and psychosocial treatment for schizophrenia, this
population most commonly receives integrated treatment for the co-occurring
disorders within the mental health system.
Effective integrated treatment programs have used one clinical
team to provide long-term, comprehensive care (i.e., medication
and psychosocial treatment interventions) for both psychotic and
substance use disorders (80, 353). Treatment is provided in the
patient's natural environment, is matched to the patient's
motivational state, provides comprehensive community services (e.g.,
stable housing, financial assistance through entitlements, vocational
rehabilitation), and is not limited in duration (80, 387). Integrated
treatment often begins by stabilizing a patient's psychotic
symptoms, which may require psychiatric hospitalization. Integrated
treatment programs can then initiate substance abuse treatment when
the patient is sufficiently stable to participate in the psychosocial
treatments for the psychiatric and substance use disorders. Thus,
the acute stabilization phase may initially emphasize appropriate
antipsychotic and psychosocial treatments that help stabilize the
illnesses (353, 371).
Existing studies and reports from expert consensus meetings
on co-occurring disorders support the same first-line agents recommended
in APA's Practice Guideline for the Treatment
of Patients With Schizophrenia (388) for individuals
with co-occurring schizophrenia and substance use disorders (80, 288).
With the possible exception of clozapine for patients with treatment-resistant
symptoms, antipsychotics generally have similar efficacy in treating
the positive symptoms of schizophrenia (389), although there is
emerging evidence and an ongoing debate regarding whether second-generation
antipsychotics may have superior efficacy in treating global psychopathology
and cognitive, negative, and mood symptoms (388). Various smaller
studies have found better outcomes with clozapine (390–398),
risperidone (394, 399–402), and olanzapine (403, 404) than
with first-generation antipsychotics for patients with co-occurring
schizophrenia and substance use disorders. However, most of these
studies were retrospective, nonrandomized, or uncontrolled pilot
studies. Furthermore, no evidence to date suggests that any one
second-generation antipsychotic is more efficacious than another
in this population, and no trials have been reported that compare
these agents in the same clinical study. Some have thought that
clozapine should be considered as a first-line agent in patients
with schizophrenia co-occurring with a substance use disorder because
of the number of studies supporting its use (394) and its ability
to reduce the risk of suicidal behaviors (405). In addition, clozapine
may have beneficial effects in decreasing smoking (406–408). However,
most experts have continued to recommend clozapine as a second-line
agent (288) because of the need for regular monitoring of the patient's
white blood count to detect granulocytopenia or impending agranulocytosis,
as well as other concerns about clozapine's side-effect
profile (i.e., increased seizure risk and sedation). Because significant
nonadherence to clozapine necessitates the retitration of the medication
dose and because blood monitoring is an essential part of clozapine
treatment, clozapine is generally used in more motivated patients
and in well-integrated treatment programs.
In choosing an antipsychotic medication, a clinician should
assess patient preferences and vulnerabilities regarding side effects,
interactions with abused substances, and other safety considerations.
It should be noted that individuals with schizophrenia who abuse
alcohol and cocaine may have an increased risk for seizures or liver
toxicity and may have cardiac abnormalities as a result of their
substance use. Medications that may induce QT prolongation should
be used with caution, with electrocardiographic monitoring as needed. Because
most antipsychotic medications are hepatically metabolized and can
lower seizure threshold to some degree, these factors should also
be taken into consideration when choosing among antipsychotic medications.
Patients with schizophrenia may also experience increased somnolence
and orthostatic hypotension if they abuse alcohol or other sedating drugs
while taking antipsychotic medications. Tobacco smoking substantially
lowers blood levels of clozapine, olanzapine, and numerous first-generation
antipsychotics (e.g., haloperidol, fluphenazine, chlorpromazine,
thioridazine) by increasing cytochrome P450 (CYP) 1A2 enzyme hepatic
metabolism, a moderate effect that may necessitate an increase in
the medication dose. The metabolism of other second-generation antipsychotics
is not significantly affected by changes in smoking status.
Another clinically important issue in this population is addressing
poor adherence with both pharmacological and psychosocial interventions.
The use of long-acting, injectable antipsychotic medications can
help increase medication adherence. A long-acting, injectable form
of the second-generation antipsychotic risperidone is available
as are long-acting decanoate preparations of first-generation antipsychotics
(i.e., haloperidol, fluphenazine); there have been no direct comparisons
of these long-acting first- and second-generation antipsychotic
agents in this population.
In general, medications targeting specific substance use disorders
can be safely prescribed for patients with co-occurring schizophrenia
and substance use disorders (288). However, careful assessment is
indicated before initiating treatment with disulfiram. Given the
cognitive difficulties associated with schizophrenia, disulfiram
should be reserved for use in individuals whose judgment and memory
are adequate and for whom impulsivity is not a significant concern.
In addition, there may be some further concern about using high-dose
disulfiram in this population because carbon disulfide, a metabolite
of disulfiram, inhibits dopamine 
-hydroxylase,
increases dopamine levels, and could potentially worsen psychosis
(409, 410). Specific studies also support the use of naltrexone
for alcohol dependence and methadone for opioid dependence in this
population (411–413). The treatment of nicotine dependence
with NRTs (i.e., nicotine patch, gum, spray, inhaler, or lozenge)
and bupropion has helped improve treatment outcomes for tobacco
smokers with schizophrenia (414, 415). There is a theoretical concern
that bupropion may increase psychotic symptoms; however, this concern
has not been borne out in studies to date (414). There are improved outcomes
with combining NRT and bupropion with psychosocial treatments that
are specific to nicotine dependence (348, 416).
+
2) Psychosocial treatments
Integrated psychosocial treatments for individuals with co-occurring
schizophrenia and substance use disorders most commonly occur in
mental health settings and include unique psychotherapy approaches
as well as modified treatment programs and systems (352). One key
aspect of integrated treatment is that patients do better when clinicians
are able to maintain an optimistic, empathic, and helpful approach
(417). Integrated programs often provide comprehensive services,
including active outreach and case management in the community setting,
in an effort to better engage and retain patients and help them
transition between different levels of care (370, 417). Model integrated
treatment programs have been described and evaluated in the literature
(417), including assertive community treatment teams and integrated
stage-based motivational models; these models tend to emphasize
a recovery-oriented perspective while combining medications, MET,
relapse prevention therapy, social skills training, and specific
dual recovery therapy approaches (80, 371, 386, 418, 419). Other
helpful components to integrated treatment programs include contingency management
and money management (360, 372). Money management helps patients
prevent relapse, given that many receive Social Security disability
or Supplemental Security Income payments and are most vulnerable
to substance use and relapse soon after receiving these funds (372).
+
b. Depressive disorders
Major depressive and substance use disorders commonly co-occur
in clinical populations and in the community (341, 343, 344, 420).
Studies have demonstrated that individuals diagnosed with major
depressive disorder have high lifetime co-occurrence rates of alcohol
abuse (men 9% and women 30%) and alcohol dependence
(men 24% and women 48.5%) (421). Among individuals
with major depressive disorder, approximately 25% have a
co-occurring substance use disorder (422). A large prospective,
longitudinal study has demonstrated that alcohol and drug use disorders
during adolescence predict later development of major depressive
disorder in young adults (423).
Mood disturbance is one of the most common symptoms reported
by individuals in substance use disorder treatment programs. In
addition to the high rate of co-occurring major depressive and substance
use disorders, patients in substance use disorder treatment settings
frequently experience substance-induced mood disorders in which
signs and symptoms of depression are related to acute substance
intoxication or to acute or protracted withdrawal from substances;
these symptoms remit with maintained abstinence (424). Because it
is often difficult for a clinician to discern whether a cluster
of symptoms is due to co-occurring major depressive disorder, substance
intoxication, substance withdrawal, substance-induced mood disorder,
or some combination thereof, guidelines have been established for
diagnosing and treating mood symptoms in the context of a substance
use disorder (425). When possible, it is advisable to delay antidepressant
pharmacotherapy by 1–4 weeks, depending on the nature and
severity of the mood symptoms, to allow the clinician to identify
substance-induced mood symptoms that may remit without medication intervention.
In general, treatment of depressive symptoms of moderate to
severe intensity should begin concurrently or soon after initiating
treatment of the co-occurring substance use disorder, particularly
if there is evidence of prior mood episodes. In individuals without
prior episodes of depression or a family history of mood disorders,
it may be appropriate to delay the treatment of mild to moderate
depressive symptoms for the purpose of diagnostic clarification.
Clinicians are advised to monitor symptoms, assess and reassess
for suicidal ideation, provide education, encourage abstinence from
substances, and observe changes in mental status during the substance-free
period while actively considering whether antidepressant intervention
is indicated (288, 426–429).
Existing studies and expert consensus support the use of first-line
agents recommended in APA's Practice Guideline
for the Treatment of Patients With Major Depressive Disorder (430)
and substance use disorder medications for detoxification, protracted
withdrawal, and agonist maintenance treatment (288). Randomized,
controlled trials supporting the efficacy of antidepressant pharmacotherapies
for co-occurring major depressive disorder and specific substance
use disorders exist for alcohol dependence, opioid dependence, cocaine use
disorders, and nicotine dependence.
A meta-analysis of 14 well-designed placebo-controlled trials
of antidepressant medication for co-occurring major depression and
alcohol, opioid, or cocaine dependence (425) showed an overall beneficial
effect of medication on mood outcome, similar in magnitude to the
effect size observed in clinical trials involving depressed patients
without substance problems. Studies showing the largest effects
of medication on mood outcome also showed significant beneficial
effects of medication on self-report measures of substance use,
although rates of abstinence were low. The results across studies
were inconsistent, with eight positive and six negative studies.
The positive studies, those demonstrating a beneficial effect of
antidepressant medication, had low placebo response rates and were
more likely to have required at least a week of abstinence prior
to diagnosing depression and starting medication. The evidence for
medication effectiveness was more consistent among studies of patients
with alcohol dependence than among studies of patients with drug
dependence, in agreement with the conclusion of another recent meta-analysis
(430a).
Of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine
(431) and sertraline (432–434) have been studied in the
treatment of co-occurring major depressive disorder and alcohol
dependence, and evidence is also available for the use of nefazodone
(435, 436) and the tricyclic antidepressants (TCAs) imipramine (428, 437) and desipramine (438). These agents, however, have not been
compared with each other nor has there been an adequate number of
studies of other SSRIs to make recommendations for specific antidepressants
as first-line agents in this population. A review of the literature
indicates that antidepressant treatment is more effective in ameliorating
mood symptoms than in improving drinking outcomes for this dually
diagnosed population (439). Given the reported risks of hepatotoxicity
and death with nefazodone use (440), this medication is not generally
recommended unless other therapies have failed.
The evidence base for antidepressant pharmacotherapy in co-occurring
opioid dependence and major depressive disorder is inconsistent
and well studied only in methadone-maintained populations. Results
of randomized, placebo-controlled trials of TCA treatment are mixed,
with some showing no differences between antidepressant treatment
and placebo (441–443) and others showing superior efficacy
of TCAs compared with placebo (444–447). Evidence for SSRI
efficacy in the same population is weaker (448), and many studies have
failed to demonstrate beneficial effects of SSRIs on mood symptoms
(413, 449, 450). Nevertheless, the relative safety of SSRIs as compared
with TCAs in this population continues to influence the choice of
SSRIs as first-line agents for patients with co-occurring opioid
use disorder and major depressive disorder. Although the duration
of antidepressant treatment in these studies was not >3 months,
there are no available data to suggest that the duration of an antidepressant
trial should be different than that used for treating major depressive
disorder without a substance use disorder.
Treating mood symptoms in individuals with co-occurring cocaine
use and major depressive disorders is complicated by the frequent
occurrence of depressive symptoms during acute withdrawal from cocaine.
Some randomized, controlled trials support the use of antidepressant
intervention in these individuals (451, 452); this population also
appears to have a more favorable mood response to TCAs than to SSRIs
(453).
Nicotine dependence commonly co-occurs with major depressive
disorder. In large well-designed, placebo-controlled trials, the
antidepressant medications bupropion (158, 454) and nortriptyline
(455, 456) have been found to improve smoking cessation rates and to
prevent relapse after successful quit attempts. Smokers with a current
major depression were excluded from these studies. The beneficial
effects of both nortriptyline (456) and bupropion (454, 1587) have
been shown not to depend on a past history of major depressionthat
is, the medications are equally effective for smokers with and without
past depression. An analysis of mediators of treatment effect (456)
suggested nortriptyline improves smoking cessation by reducing postquit
dysphoria, with the effect, again, independent of past history of
major depression. Serious depression sometimes emerges after a patient
has successfully quit smoking (457, 457a, 763), suggesting the importance
of monitoring mood during quit attempts. Studies are needed of the
treatment of smokers with current depressive disorders. However,
in such patients, most clinicians will prioritize stabilization
of the depressive episode and then subsequently address treatment
of nicotine dependence during the maintenance phase of depression
treatment (348). Sustained-release bupropion for treating nicotine
dependence may be safely added to other antidepressants (e.g., SSRIs, which
do not alter smoking cessation rates) being used to treat major
depressive disorder (458). NRTs are also recommended as a first-line
option in treating nicotine dependence in depressed smokers. In
addition, integrating standard tobacco dependence–related
psychosocial treatment into ongoing psychosocial treatment for depression
improves both tobacco dependence and depression outcomes among smokers
with recurrent depression and heavy smoking (459).
Many patients with co-occurring major depressive and substance
use disorders will report experiencing insomnia or anxiety symptoms.
Such symptoms are optimally addressed using behavioral strategies
(e.g., stress reduction, relaxation skills, adherence to sleep hygiene)
and/or pharmacological interventions with medications that
do not have a potential for abuse (e.g., buspirone) before medications
with abuse potential (e.g., benzodiazepines, nonbenzodiazepine hypnotics
such as zolpidem) are considered. Although not specifically studied
in co-occurring major depressive and substance use disorders, the
antidepressant trazodone may represent an additional option (see
Section II.G.2.c).
In the context of continued substance use, inadequate symptom
improvement should not lead the clinician to conclude that a medication
regimen is a therapeutic failure. Patients with persistent depression
and substance use may benefit from more frequent outpatient visits
or referral to a higher level of care (e.g., intensive outpatient,
partial or residential hospitalization, inpatient treatment).
+
2) Psychosocial treatments
Integrated psychosocial therapies have been developed, and
their efficacy is being tested in controlled trials for patients
with co-occurring major depressive disorder and substance use disorders
(456, 460, 461). These psychotherapy approaches combine traditional
therapies for substance use disorders (e.g., MET, TSF, relapse prevention
therapies, CBT, contingency management) with traditional therapies
for depression (e.g., cognitive therapy, behavioral therapy, IPT,
and brief psychodynamic therapy) (357, 462). These approaches commonly
try to help patients identify and manage triggers for substance
use, understand and manage feelings, deal with grief and anger,
change thoughts and beliefs that worsen mood, improve relationships,
and change behaviors and lifestyles (463).
Individuals with bipolar disorder are at high risk for a co-occurring
substance use disorder; community lifetime prevalence rates of co-occurrence
are 
50% (341, 420). Substance use disorders influence bipolar disorder by worsening
each episode as well as worsening the overall course of the disorder
by causing more mixed episodes, earlier onset, more frequent episodes,
and slower symptom remission (464).
Few medication studies have been conducted with co-occurring
bipolar and specific substance use disorders; however, the existing
research (464–468) and expert consensus (469, 470) support
use of the first-line agents recommended in APA's Practice
Guideline for the Treatment of Patients With Bipolar Disorder (471)
and the use of adjunctive medications that target specific substance
use disorders. The few medication studies examining co-occurring
bipolar and substance use disorders support the use of valproate
(or valproic acid or divalproex) as a mood stabilizer because it shows
some evidence of efficacy and appears to help overall treatment
adherence (472). In addition, some evidence suggests that patients
with these co-occurring disorders are more likely to respond to
valproate or a combination of valproate plus lithium than to lithium alone
(465–468, 472, 473). The relative lack of efficacy with
lithium may be due to an increase in side effects or the difficulty
that patients with co-occurring bipolar and substance use disorders
have in achieving stable lithium blood levels. The use of carbamazepine
in this population is supported by a few studies with positive outcomes
(474). There is only one small pilot study to date evaluating the
role of second-generation antipsychotics in patients with co-occurring
substance use and bipolar disorders (475). Therefore, treatment recommendations
follow those presented in APA's Practice
Guideline for the Treatment of Patients With Bipolar Disorder (471),
with first-line pharmacological treatment for more severe manic
or mixed episodes with lithium or valproate plus an antipsychotic.
For less ill patients, monotherapy with lithium, valproate, or an
antipsychotic may be sufficient. Second-generation antipsychotics
are generally preferred over first-generation antipsychotics because
they appear less likely to cause tardive dyskinesia and extrapyramidal
side effects; however, the possibility of weight gain, diabetes,
and hyperlipidemia with these agents requires consideration. Second-generation
antipsychotic agents with an FDA indication for use in treating
acute manic or mixed episodes in bipolar disorder include olanzapine,
risperidone, ziprasidone, and aripiprazole. Quetiapine has an FDA
indication for the treatment of acute episodes of mania. In the
acute setting of a manic episode, a benzodiazepine may be helpful.
However, the general concern about using a medication with high
abuse potential must be considered; therefore, caution should be
exercised in using benzodiazepines beyond the time period of the
acute manic episode. For mixed episodes, valproate may be somewhat
more efficacious and thus may be preferred over lithium (465–468).
Pharmacological alternatives to lithium and valproate include carbamazepine
or oxcarbazepine. The possibility of pregnancy should be considered
when prescribing valproate or carbamazepine for women of childbearing
age, particularly given the increased risk of neural tube defects
if the fetus is exposed to these medications in utero.
Because there are no specific studies of the treatment of
bipolar depression in substance-abusing individuals, medication
strategies should follow the recommendations for managing bipolar
depression described in APA's Practice
Guideline for the Treatment of Patients With Bipolar Disorder (471).
The guideline recommends the initiation of lithium or lamotrigine
as a first-line pharmacological treatment. Lamotrigine should be
used cautiously in individuals with co-occurring bipolar and substance
use disorders because active substance users may be unreliable in
reporting rashes; gradual titration of lamotrigine is needed and
may be problematic in individuals who may be inclined to take excess
medication doses, and drug-drug interactions may alter lamotrigine
levels and increase the risk of rash (476). Antidepressant monotherapy
is not recommended due to concerns about precipitating a mixed or
manic episode or contributing to the development of rapid cycling.
As an alternative, especially for more severely impaired patients,
some clinicians will initiate simultaneous treatment with lithium
and an antidepressant. Also, IPT and CBT may help treat symptoms
of bipolar depression when they are added to pharmacotherapy.
Integrated psychosocial treatments for bipolar and substance
use disorders have been developed and demonstrated to be effective
by Weiss et al. (369). The group therapy–based treatment
approach in this study integrated cognitive-behavioral approaches
that were effective in treating both disorders. The approach has
been described in a clinical treatment manual for clinicians that
includes educational, motivational, and coping strategies to enhance
medication adherence and self-efficacy with cues and triggers for
drug use (369).
Although nicotine dependence is common among individuals with
bipolar disorder, there have been no reports on treating nicotine
dependence in this population (348). Recommendations for treating
co-occurring bipolar disorder and nicotine dependence are to integrate
the standard somatic and psychosocial treatments for nicotine dependence
(see Section III) into the context of the maintenance phase of treating
bipolar disorder.
Symptoms of anxiety and anxiety disorders commonly co-occur
with substance use disorders (341). Based on a sample of individuals
between ages 15 and 54 years, lifetime rates of anxiety disorders
(including GAD, panic disorder, specific phobia, social phobia,
obsessive-compulsive disorder, PTSD, and acute stress disorder)
in the community are estimated to be about 19% in men and
31% in women (341). About 50% of individuals with
a substance use disorder have an anxiety disorder (341, 420), with
different rates for different anxiety disorders. For example, about
4.5% of patients with a substance use disorder have panic
disorder, and 16% of panic disorder patients have a co-occurring
substance use disorder (341). Despite the high prevalence rates,
anxiety disorders are frequently underdiagnosed in substance abuse
treatment settings (477). Because many substances cause state-dependent
anxiety symptoms (i.e., during intoxication, acute withdrawal, or
protracted withdrawal), the assessment of anxiety disorders in substance-using
populations is challenging and requires careful assessment. The
clinician should ask about symptoms that relate to specific anxiety
disorders and use similar considerations during the assessment process
to those recommended for depression symptoms and substance use disorders.
Although nicotine dependence is also common among individuals with
anxiety disorders, there are almost no treatment studies for this
population, and treatment should follow the standard somatic and
psychosocial treatment recommendations for nicotine dependence (see
Section III).
Integrated treatment for co-occurring anxiety and substance
use disorders may include medications and psychosocial treatments
from both substance abuse and psychiatric treatment perspectives.
Specific medications and CBTs for specific anxiety disorders have
been developed and can be combined with the usual treatments for
substance use disorders. Providing education about the anxiety and
substance use disorders and the effects the disorders have on each
other is also important.
The recommended medications for treating panic disorder with
a co-occurring substance use disorder are SSRIs plus integrated
psychosocial treatment (288, 478). If several SSRIs are tried and
found to be ineffective, then a TCA may be considered; however,
TCAs may be of concern when using them in the context of co-occurring
substance use disorders because of the risk of cardiac toxicity
and seizures and the potential for overdose in a suicide attempt.
Although benzodiazepines are usually considered a first-line treatment
for panic disorder in patients without an active substance use disorder,
the risk of benzodiazepine abuse is a significant concern and precludes
this class of medications from being first-line agents in treating
panic disorder in the context of a coexisting substance use disorder.
In rare cases, physicians have treated severe panic symptoms by
using benzodiazepines on a time-limited basis, selecting patients
without a history of misusing benzodiazepines but who have a family
history of panic disorder, and fully informing the patient and sometimes the
family of the risks of taking benzodiazepines. Physicians may also
limit prescriptions, supervise medication administration, monitor
medication adherence with pill counts, and request that patients
come for more frequent office visits while patients are taking benzodiazepines.
Two double-blind, placebo-controlled studies have demonstrated the
efficacy of buspirone in patients with alcohol dependence and anxiety
(479, 480).
Pharmacotherapy for social anxiety disorder in the context
of co-occurring substance use disorder may include beta-blockers
or SSRIs along with integrated psychosocial treatment. In a recent
study in which simultaneous treatment of social anxiety disorder
and co-occurring alcohol dependence was compared with treatment
of alcohol dependence alone, both treatment conditions improved
alcohol-related outcomes and social anxiety; however, treatment
focused on alcohol only was associated with better alcohol use outcomes
(481). Although more studies of concurrent treatments for social
anxiety and substance use disorders are needed, these findings suggest
that combination treatment of social anxiety and alcohol use disorders
may not be effective for all patients.
The treatment of obsessive-compulsive disorder in the context
of a co-occurring substance use disorder uses pharmacotherapy with
SSRIs and integrated psychosocial treatment. TCAs, including clomipramine,
may be of concern for use in patients with co-occurring substance
use disorders because of the risk of seizures and the potential
for overdose in a suicide attempt. Second-generation antipsychotics
may be an option for some individuals (288).
GAD commonly co-occurs with other psychiatric and substance
use disorders. CBT approaches can be particularly helpful for symptoms
of preoccupation/rumination and exaggerated perceptions
of danger. First-line agents for this population include buspirone
and SSRIs. Although benzodiazepines may be used chronically in GAD
patients with no substance use disorder, their use should be limited
or applied in only the previously described circumstances in patients
with a substance use disorder because of their abuse potential (288).
PTSD is common among individuals with a substance use disorder
(about 20%), with women having about twice the rate of
co-occurring PTSD as men (482); however, clinicians are advised
not to overlook the possibility of PTSD in male patients, because
in the general community, rates of PTSD are higher for men than
for women (483). Rates of PTSD appear to be high in substance use
disorder treatment settings, with one study reporting that 40% of
95 substance- abusing/dependent inpatients met criteria
for current PTSD (484). Women with PTSD and a substance use disorder
often experienced childhood physical and/or sexual abuse,
whereas men typically experienced combat or were victims of crime (483).
PTSD symptoms are a common trigger of substance use, and patients
may perceive the substances as a way of coping with overwhelming
emotional pain (485–488). Indeed, one study showed that
individuals with PTSD and either cocaine or alcohol dependence experienced
increased craving when exposed to both trauma and drug cues (489).
As patients with co-occurring PTSD and a substance use disorder
participate in treatment and become able to maintain continued abstinence,
they may feel overwhelmed by a flood of memories and unprocessed
feelings about the past traumas that have been masked by substance
use (490). Simply because patients have become abstinent from substances
does not mean that symptoms of PTSD have resolved, and these will
need to be addressed in treatment (491, 492). Patients may carry
a great burden of shame and guilt, as both PTSD and substance abuse
may be associated with keeping secrets and denial. These individuals
are sometimes perceived as "crazy," "lazy," or "bad" by
others and by themselves, and these issues are similarly important
to anticipate in psychotherapy (490).
Specific integrated psychotherapies for PTSD co-occurring
with a substance use disorder have been developed and evaluated
(365, 368, 490). These approaches have similar components in that
they educate the patient about both disorders and how the two problems interact
to worsen the course of either disorder alone. Treatment focuses
on stabilizing the substance use disorder and developing coping
skills to manage the PTSD symptoms and trauma memories as they occur
during the early phase of abstinence as well as after prolonged
periods of abstinence (490). Seeking Safety (490), an empirically
tested group treatment for patients with PTSD and a coexisting substance
use disorder, and integrated treatment approaches that combine the
12-step treatment model from substance use disorder treatment with
traditional psychotherapeutic approaches to PTSD have been developed to
treat this patient population (493, 494). One study of 107 women
were randomly assigned to receive Seeking Safety treatment, a manual-guided
relapse prevention therapy, or standard community treatment found
that women receiving Seeking Safety or relapse prevention therapy
had significant reductions in substance use, PTSD, and psychiatric
symptoms over the 3-month treatment period, whereas the symptoms
of women who received standard community treatment worsened (364);
furthermore, the Seeking Safety and relapse prevention groups maintained
the greater improvements in substance use and PTSD symptoms at the
6- and 9-month follow-ups. Outcomes did not differ between the Seeking Safety
and relapse prevention groups.
Many integrated treatment approaches discourage having the
patient describe or explore traumatic memories as might be done
in exposure therapy. Only a few pilot studies have been published
that evaluate trauma exploration therapies (e.g., exposure therapy)
in substance-abusing patients (365, 368). In those few studies,
positive results were generally reported. One recently published
effectiveness trial of integrated exposure-based therapy for PTSD
and psychosocial treatment of substance use disorders reported feasibility
and clinical effectiveness within an inner-city mental health treatment
setting serving dually diagnosed patients (366). Future research
is needed to define which patients may benefit from this type of
treatment. Other psychosocial treatments used to treat PTSD are
being considered for adaptation to patients with PTSD and a co-occurring
substance use disorder; these include mourning therapy (495), eye
movement desensitization and reprocessing (496), and the counting
method (497).
Medication recommendations for treating PTSD in the context
of a co-occurring substance use disorder follow the general recommendations
from APA's Practice Guideline for the Treatment
of Patients With Acute Stress Disorder and Posttraumatic Stress
Disorder (498). The SSRIs are considered first-line
medication treatment for PTSD. Given the abuse potential of benzodiazepines,
prescribing them to patients for the treatment of PTSD presents
a risk for substance relapse and/or the development of
a new substance use disorder.
+
e. Attention deficit hyperactivity disorder
Substance use disorders are common in adolescents and adults
with ADHD, with about 33% of adult ADHD patients having
a history of an alcohol use disorder and about 20% having
a drug use disorder; even higher prevalence rates (50%–60%)
of co-occurring nicotine dependence have been reported (341, 499).
Among patients with alcohol, cocaine, or opioid dependence, 17%–50% have
co-occurring ADHD (499). Establishing a diagnosis of ADHD can be
complicated in the context of ongoing substance use, because attention
problems are often caused by the acute and prolonged effects of
specific substances of abuse, and these attention problems will
often improve with prolonged abstinence. On the other hand, delaying
adequate treatment of co-occurring ADHD may compromise a patient's
capacity to fully participate in treatment for a substance use disorder
(500, 501). Therefore, it is recommended that treating physicians
attempt to gather evidence supporting a co-occurring ADHD diagnosis
(e.g., childhood ADHD, evidence of symptoms during prolonged abstinence
from substance use) during early assessment and treatment planning.
Clinicians are also advised to assess patients with co-occurring
ADHD and a substance use disorder for other commonly co-occurring
psychiatric disorders (e.g., learning disorders, mood and anxiety
disorders, conduct disorder/antisocial personality disorder)
(499).
The occurrence of childhood ADHD contributes independently
of other psychiatric disorders to the risk of developing an early-onset
substance use disorder (502, 503). Early interventions for childhood
ADHD (psychosocial and/or pharmacotherapy) may help to prevent
new-onset substance use disorders in this population in adulthood.
Even though stimulants are commonly recommended for the treatment
of childhood ADHD, concerns that childhood use of prescribed stimulants
may predispose an individual to a future substance use disorder
are unsubstantiated (504). In fact, a recent meta-analysis of the
literature indicated that childhood stimulant therapy lowers the
risk of developing a concurrent alcohol or drug use disorder during
adolescence and adulthood (505, 506).
Stimulant pharmacotherapy is effective for adolescent and
adult ADHD (507) and may be effective for patients with a co-occurring
substance use disorder (508–510); however, clinicians must
carefully assess symptom improvement with stimulant treatment against the
risk for misuse or diversion of prescribed stimulants. Prescription
monitoring (e.g., limited dispensing, medication logs) and the use
of long-acting stimulant preparations and standardized clinical
symptom assessments (511, 512) are recommended. When there is concern
about the safety of stimulant treatment in patients with ADHD and
a substance use disorder, alternative ADHD pharmacotherapies without
an abuse potential may be considered, such as atomoxetine, bupropion,
and desipramine (513).
ADHD symptoms often interfere with a patient's adherence
to substance use treatment, and therefore integrated psychosocial
and pharmacotherapy treatment is recommended for patients with ADHD
and a substance use disorder (501, 514). Although integrated psychosocial
interventions for this population are recommended, research to support
their use is limited. Expert consensus recommends providing patients
with education about both disorders, encouraging their active participation
in support groups, and modifying psychosocial treatments to facilitate
learning (e.g., using brief structured sessions with written handouts) (288, 499).
Epidemiological studies indicate an association between bulimia
nervosa and substance use disorders, but not between anorexia nervosa
and substance use disorders (515). Bulimia nervosa is more common
among individuals with a substance use disorder than in the general
population (515). Inpatient substance abuse treatment studies report
that about 15% of women and 1% of men have an
eating disorder; this group is more likely to abuse stimulants and
less likely to use opioids than individuals without an eating disorder
(515). In clinical samples, substance use disorders have been found
to be common among patients with bulimia (about 23%) (516)
and less frequent among those with anorexia nervosa (about 15%)
(515). The types of agents abused by individuals with an eating
disorder include diet pills, stimulants, laxatives, diuretics, emetics,
and many other substances (515, 517). With chronic use, tolerance
to the effects of and withdrawal from these medications can occur. Tobacco
use and dependence are also common among individuals with bulimia
and anorexia nervosa and may be linked with attempts to lose weight.
Individuals with co-occurring bulimia and substance use disorders
are more likely to be younger when they seek treatment for their
bulimia nervosa and have an earlier onset of problem drinking compared
with those individuals with bulimia nervosa only (516).
Integrated treatment may occur within psychiatric or substance
use disorder treatment programs, and can combine traditional psychosocial
treatments for substance use disorders with treatments for bulimia,
including relapse prevention or CBT strategies (e.g., identifying
automatic thoughts, thought restructuring, identifying cues and
triggers for bingeing/purging and substance use). Substance
abuse treatment programs may need to add nutritional consultation
and education for these patients, help them set goals for an acceptable
weight range, and observe them at and between meals for bingeing
and/or purging behaviors (515, 518). The 12-step recovery–oriented
community groups for both disorders (such as AA and Overeaters Anonymous)
can provide additional structure and support.
Medication strategies to treat bulimia or anorexia nervosa
should follow the recommendations in APA's Practice
Guideline for the Treatment of Patients With Eating Disorders (518).
There are no controlled medication trials to guide treatment of
bulimia nervosa co-occurring with a substance use disorder. Naltrexone
may be worth considering for patients with co-occurring alcohol
dependence and bulimia nervosa, given its clinical utility in bulimic
patients (519, 520) and its established use with alcohol use disorders
(see Sections IV.C.3.a and IX.B.3.a).
+
g. Personality disorders
Personality disorders and substance use disorders commonly
co-occur, with an estimated 50%–60% of
individuals with a substance use disorder having a co-occurring
personality disorder (463, 521). Prevalence rates of borderline
personality disorder (BPD) are approximately 30%–50% across
inpatient, outpatient, and community samples of individuals with
a substance use disorder (522). Antisocial personality disorder
(ASPD) has a lifetime prevalence of 60% among injection
drug users (523, 524), although there are recognized problems with
the accuracy of an ASPD diagnosis in patients with a co-occurring
substance use disorder due in part to drug-associated criminal behavior
(525) and overlap with BPD (318). Establishing a personality disorder
diagnosis in the context of a substance use disorder can be difficult
and may be best done after a patient has achieved a prolonged period
of abstinence from substance use. Because patients with a substance
use disorder and BPD or ASPD have higher-risk behaviors and a higher
suicide risk (303, 318, 526) as well as poorer treatment outcomes
(527–532), improved instruments for assessing a co-occurring
personality disorder in this context would help to identify high-risk
patients who may require more intensive treatments.
Integrated treatments for this population initially focus
on helping the therapist manage countertransference issues, develop
a therapeutic alliance, and integrate existing behavioral therapy
approaches for personality disorders into the substance use disorder
treatment. Specific integrated psychosocial therapies that combine
traditional substance use disorder treatment with the treatment
of a personality disorder have been developed to address these co-occurring
disorders (373, 374, 463). Although dialectical behavioral therapy
has been shown to be effective for treating BPD with or without
a co-occurring substance use disorder, it is not always effective
in improving substance use outcomes (533), and there remains a need
for improved integrated therapies for this high-risk population.
There have been few medication studies for co-occurring personality
and substance use disorders. Medication recommendations in the APA's Practice
Guideline for the Treatment of Patients With Borderline Personality
Disorder (534) may be used to guide treatment.
In some cases, medications for personality disorders are used episodically
to treat specific symptoms. Benzodiazepines should be used with
caution in patients with co-occurring personality and substance
use disorders due to the risk of benzodiazepine abuse (535) and
overdose and suicide attempts (536).
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h. Pathological gambling
Individuals with a substance use disorder are vulnerable to
other non-substance-related compulsive behaviors such as pathological
gambling and compulsive sexual behaviors. Only pathological gambling
is recognized as a DSM-IV-TR disorder. Individuals with a substance
use disorder have about a four- to fivefold higher rate of pathological
gambling when compared with the general population, and studies
suggest that about 15% of substance abusers meet criteria
for pathological gambling (537–539). The National Epidemiologic
Survey on Alcohol and Related Conditions, a large nationally representative community
study, reported that among adults with a lifetime history of pathological
gambling, 73% have had a co-occurring alcohol use disorder,
38% have had a co-occurring drug use disorder, and 60% have
had co-occurring nicotine dependence (540). It is likely that pathological
gambling, though common, is underdiagnosed, because substance abuse
or psychiatric treatment settings do not always screen for it (541).
Individuals with pathological gambling and a substance use disorder
are also at increased risk for engaging in unsafe sexual behaviors
and having mood or anxiety problems, ADHD, ASPD, or legal problems (537, 539, 542, 543).
Integrated treatment programs rarely include pathological
gambling treatment and generally do not provide Gamblers Anonymous
meetings on-site (542, 544). However, integrated treatment could
readily incorporate behavioral therapies for pathological gambling that
are similar to traditional substance use disorder treatment, such
as gambling relapse prevention strategies, social skills training,
problem solving, and cognitive restructuring (544).
Medications that appear to help reduce the desire to gamble
and gambling behaviors have not been examined in individuals with
a co-occurring substance use disorder. Medications studied in pathological
gambling alone include fluvoxamine (545–547) and naltrexone
(548, 549). A large, multicenter, randomized, controlled trial of
paroxetine plus psychosocial treatment failed to demonstrate a significant
difference from placebo (550), and an open-label, flexible-dose
study of sertraline also failed to demonstrate superiority to placebo
(551). Lithium and valproate may be effective in the treatment of
pathological gambling for those with bipolar disorder (552, 553).
In general, medication trials for pathological gambling show a high
early placebo rate; longer-duration studies may be needed to confirm
the positive effects of medication.
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3. Comorbid general
medical disorders
Concurrent general medical conditions frequently complicate
the treatment of substance use disorders. A full description of
the medical problems associated with substance use disorders is
beyond the scope of this practice guideline and has been provided
elsewhere (554, 555).
Substance use causes a variety of health problems (Table 3),
which vary depending on the substance used and its route of administration.
These medical problems may be further complicated by the use of
multiple substances and nutritional deficiencies that may accompany
ongoing substance use. Many substance use disorder patients with
a co-occurring medical disorder do not seek or receive adequate
general medical care for a variety of reasons, including the chaotic
and disorganized lifestyles often associated with substance abuse
and these patients' lack of access to health care. Physicians
may be reluctant to adequately treat the pain of individuals who
have a painful medical condition but also a current or past substance
use disorder (556). Thus, the substance abuse treatment encounter
may be the first opportunity to address the general medical care
needs of these patients.
At present, the medical risks associated with marijuana use
are not well understood. Because it is likely that marijuana contains
many of the same carcinogens as cigarettes, it is possible that
lung cancer may occur in marijuana smokers, although there is no
evidence to support this (557).
Substance use–related conditions such as hepatitis
and tuberculosis and associated events such as motor vehicle accidents,
falls, suicide, and homicide contribute to an increased risk of
death and disability in the substance-using population. Tobacco-related medical
disorders are a greater cause of mortality than alcohol-related
medical disorders among individuals dependent on alcohol or other
nonnicotine substances (558). This finding highlights the importance
of assessing substance-abusing patients for tobacco use and recommending
psychosocial and/or pharmacological intervention that will
help them quit. Among individuals who inject drugs, infectious diseases
are the most common cause of general medical comorbidity. Approximately
30%-40% of inner-city intravenous drug users test
positive for HIV (559, 560), and depending on the treatment setting,
as many as 30%–75% of substance use disorder
treatment patients have been diagnosed with hepatitis C. Indeed,
intravenous drug use accounts for 60% of new cases of hepatitis
C and 25% of new HIV infections per year (561). Regardless
of treatment setting, the adoption of universal precautions against
body contamination by infectious agents is a necessary part of protecting
staff and patients against the spread of HIV (562).
The risks of contracting sexually transmitted diseases commonly
differ between the sexes. Among individuals with severe psychiatric
disorders, men with hepatitis C have increased lifetime rates of
drug-related risk behaviors (e.g., needle use, needle sharing, crack cocaine
use), whereas women have higher lifetime rates of sexual risk behaviors
(e.g., unprotected sex in exchange for drugs, money, or gifts; unprotected
vaginal or anal sex) (563). All substance-using patients should
be counseled about safe sex practices and taught specific interpersonal
skills (e.g., assertiveness, negotiation) for discussing and requiring
the use of safe sex practices with their partners. Gender-specific
group treatments using educational/skills building approaches
have been developed and are being studied (e.g., in the National
Institute on Drug Abuse [NIDA] Clinical Trials
Network studies to reduce HIV-related and sexually transmitted disease–related
risk behaviors in patients in substance abuse treatment). Needle
exchange programs and effective treatment of the substance use disorder
and HIV or hepatitis C also reduce the spread of HIV and hepatitis
C infection (561, 564).
When treating HIV-seropositive, opioid-dependent individuals
with antiretrovirals and methadone, the physician needs to be aware
of the clinically significant interactions between these two medications
that can decrease the efficacy of antiviral medications and/or require
methadone dose adjustments (565). It is recommended that individuals
with hepatitis C receiving treatment with interferon be assessed
for lifetime or current major depressive disorder because of the
frequent development and/or exacerbation of depressive symptoms
during treatment with interferon (566). All patients receiving interferon
should be monitored for the development of depression, and consideration
should be given to initiating antidepressants and counseling. Guidelines
for the psychiatric treatment of patients with HIV or AIDS are available
in the APA's Practice Guideline for the
Treatment of Patients With HIV/AIDS (567).
The rise of treatment-resistant tuberculosis among patients
with a substance use disorder suggests the need to consider periodic
tuberculosis screening for patients and staff who treat these patients,
along with efforts to reduce the spread of tuberculosis in treatment
environments. Supervised on-site chemoprophylaxis or treatment for
tuberculosis within substance abuse treatment programs is also strongly
recommended (568, 569).
The treatment of substance use disorders is crucial in the
pregnant woman because ongoing substance use during pregnancy has
the following multiple implications for both the mother and the
developing fetus:
- The
health of the pregnant woman. Pregnant women with
a substance use disorder are at high risk for sexually transmitted diseases
(e.g., HIV infection), hepatitis, anemia, tuberculosis, hypertension,
and preeclampsia (570, 571). In addition, the presence of a substance
use disorder may affect a woman's ability to maintain a
healthy lifestyle, including proper nutrition and prenatal care.
- The course of the pregnancy. Women
with certain substance use disorders may be at greater-than-average
risk for spontaneous abortions, preeclampsia, abruptio placentae,
and early and prolonged labor (572–574), in addition to
complications of other general medical conditions that may be attributable
to the substance use (e.g., hypertension in cocaine users) (575).
- Fetal development. Some
abused substances, including nicotine, opioids, cocaine, and alcohol,
are known to pass through the placenta and directly affect fetal
metabolism and development (576–578). This may happen at
any stage of development but is particularly likely during the third
trimester, when maternal fetal blood flow and rates of placental
transport are increased. Fetal concentrations of abused substances
average 50%–100% of maternal blood levels
and may be higher than maternal blood levels (579). The circulation
of active metabolites is another source of fetal exposure to potentially
toxic substances. The fetus may be at higher-than-average risk for
birth defects, cardiovascular problems, impaired growth and development,
prematurity, low birth weight, and stillbirth (573, 580–585).
After delivery, the neonate may experience withdrawal from the substance,
which may be difficult to recognize, particularly if the pediatrician
is unaware of the mother's substance use disorder.
- Child development. Some
substances (e.g., alcohol) are associated with long-term negative
effects on physical and cognitive development, as is seen in fetal
alcohol spectrum disorders (586–588).
- Parenting behavior. In
addition to ongoing treatment for the disorder itself, mothers with
a substance use disorder are frequently in need of education and
training in parenting skills, social services, nutritional counseling,
assistance in obtaining health and welfare entitlements, and other
interventions aimed at reducing the likelihood of child abuse or
neglect (589, 590). This is particularly true of women with co-occurring
substance use and psychiatric disorders.
Goals for the treatment of pregnant, substance-using women
include 1) providing appropriate treatment for the substance use
disorder (e.g., methadone maintenance for opioid dependence and
abstinence from other substances, including alcohol, cocaine, marijuana,
and nicotine), 2) treating co-occurring medical or psychiatric
disorders, 3) monitoring the safety of patient behaviors during
pregnancy as well as during the postpartum period, 4) facilitating
competent parenting behaviors, and 5) motivating the patient to
remain abstinent after childbirth.
The optimal therapeutic approach is nonpunitive and maintains
patient confidentiality. Education and counseling to help women
make an informed decision about continuing or terminating a pregnancy
should be provided. Women likely to return to a substance-abusing milieu
should be counseled about long-term treatment options available
in the community.
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5. Gender-related
factors
Information on the natural history, clinical presentation,
physiology, and treatment of substance use disorders in women is
limited. Although women are estimated to comprise 34% of
all individuals with a substance use disorder other than nicotine
dependence in the United States (591), psychosocial and financial
barriers (e.g., lack of child care, lack of health insurance) prevent
many women from seeking treatment (592). Another explanation for
women's low utilization of substance use disorder treatment
services may be women's perception of greater social stigma
associated with their substance abuse (593–595). Once in
treatment, women have been found to have a higher prevalence than
men of primary co-occurring mood and anxiety disorders that require
psychiatric care (593, 596). Many women with a substance use disorder
have a history of physical and/or sexual abuse (both as children
and as adults), which may also influence treatment planning, participation,
and outcomes (597, 598). Female patients, particularly single mothers,
may have more family responsibilities and may require more help
with family-related problems. There is some evidence that tailoring
the goals of treatment to meet the needs of women improves treatment outcomes
for substance-using women (599, 600).
In terms of nicotine dependence, there is some evidence to
suggest that women may smoke less for nicotine reinforcement and
more for nonnicotine factors such as other sensory effects of smoke
inhalation, conditioned responses to smoke stimuli, and secondary social
reinforcement (601). It has also been suggested that women have
more difficulties with smoking cessation than men, although recent
studies have suggested that cessation rates are similar between
the two sexes. There is some evidence that NRT is less effective in
female smokers, but the evidence for this is not strong; any initial
failures with NRT could be followed by nonnicotine therapies such
as bupropion and clonidine (602). Two recent studies showed that
women have improved rates of smoking cessation when treated with
naltrexone in combination with either smoking cessation therapy
alone (603) or NRT and psychosocial therapy (604). Naltrexone as
an adjunctive treatment to NRT and/or smoking cessation
therapy may also be a treatment option for women who have had initial failures
with NRT, although more research is needed to support this. Factors
that may lead to poorer outcomes in women include depressive symptoms,
negative affect, and reduced social supports. Women also frequently
cite the fear of weight gain or actual weight gain after smoking
cessation as a reason for relapsing to smoking. Therefore, smoking
cessation therapies for women should emphasize weight-management
strategies.
Women may also experience more adverse physical outcomes from
tobacco use. Women may be more sensitive to secondhand smoke than
men (605), and studies indicate that women smokers are at increased
risk for lung cancer of all histological types, even after controlling
for the number of cigarettes smoked (606). Estrogen effects on carcinogenesis in
the lung may account for this difference in women.
The prevalence of smokeless tobacco use in young men over
the last several years has dramatically increased (607). This is
particularly alarming given the high rates of oral cancer associated
with smokeless tobacco use. Smokeless tobacco use should be taken
into consideration in addition to cigarette, cigar, and pipe use
during the assessment and treatment planning processes.
With regard to alcohol use, female-to-male ratios for alcohol
abuse are highest in the younger age groups, suggesting more alcohol
use among young women and a closure of the original gap in usage
rates between the sexes (596, 608). Of notable concern is the poorer prognosis
for medical sequelae of alcohol abuse and dependence in women. Alcohol-dependent
women consume less alcohol than men yet progress to late stages
of alcohol-related illness more rapidly (609) and have a shorter
time course to the initial development of alcohol-related medical
morbidity than do men. Prevalence rates of alcohol-related cirrhosis
of the liver and cardiomyopathy in women are twice that in men with
alcohol abuse or dependence. Breast cancer and mortality are increased
in women consuming more than two standard unit drinks per day (610).
Alcohol-abusing women are also at higher risk for death when compared
with same-sex, sober control populations (reviewed in Greenfield
and O'Leary [611]).
One study of individuals with a substance use disorder in
three outpatient treatment settings (methadone maintenance clinic,
intensive outpatient program for cocaine dependence, and general
outpatient substance abuse treatment clinic) showed that women with
a substance use disorder reported significantly more cardiovascular,
mood, nose/throat, CNS, skin, and gastrointestinal symptoms
related to substance use than did men (612). This occurred despite
the lack of differences between men and women in this sample in
their preference for cocaine, alcohol, or opioid drugs. Women frequently
initiate cocaine and opioid use in the context of a substance-using
partner and tend to initiate use at a younger age than men (593, 613).
+
a) Children and adolescents
An in-depth review of the evaluation and treatment of substance
use disorders in children and adolescents is beyond the scope of
this practice guideline. However, because an adult psychiatrist
may be called on to evaluate children or adolescents with a substance
use disorder, some general information and treatment principles
are reviewed here. For more detailed information, the reader is
referred to the American Academy of Child and Adolescent Psychiatry's Practice
Parameter for the Assessment and Treatment of Children and Adolescents
With Substance Use Disorders (614) and the Substance
Abuse and Mental Health Services Administration (SAMHSA) recommendations
for screening and assessing adolescents for substance use disorders (615–617).
Alcohol and other psychoactive substance use, abuse, and dependence
in children and adolescents continue to present a serious public
health problem in the United States. Alcohol and other substance
use are among the leading causes of morbidity and mortality from motor
vehicle accidents, suicidal behavior, violence, drowning, and unprotected
sexual activity in this population (618).
Regional studies reveal that 7%-10% of adolescents
are in need of treatment for substance use disorders (619). Children
and adolescents are generally more likely to have abuse rather than
dependence disorders and are less likely to appreciate the need
for entering and remaining in treatment. Abuse is not necessarily
a prodrome to dependence, and it may be developmentally limited
in many adolescents. In addition, Pollock and Martin (620) demonstrated
the importance of a new nosological entry in youth diagnoses entitled "orphan
diagnoses" that includes subthreshold symptomatology of
alcohol dependence (i.e., one or two symptoms only) but no abuse
symptoms. A 3-year follow-up study demonstrated that this entity
has a unique trajectory dissimilar to that of abuse and dependence.
Assessment and treatment of children and adolescents with
a substance use disorder must take into account their psychosocial
developmental levels and the possible role of their substance use
disorder in impeding the successful attainment of developmental
milestones, including a sense of autonomy, the ability to form interpersonal
relationships, and general integration into society. The assessment
should be multidimensional and address problems in several life
domains, including psychiatric comorbidity, school or employment performance,
family functioning, peer social relationships, legal status, and
recreational activities (621).
Children reared in family environments in which other family
members abuse or are dependent on alcohol or other substances are
at higher risk for physical and sexual abuse, particularly when
family members exhibit antisocial behaviors; these children may
exhibit psychological and behavioral sequelae (including substance
abuse) as a result (622, 623).
Most adolescents with substance use disorders also have one
or more co-occurring psychiatric disorders, most often conduct disorder
and/or major depression, although ADHD, anxiety disorders
(including social phobia and PTSD), bipolar disorder, eating disorders, learning
disabilities, and other axis II disorders are also common (624–626).
Many adolescents with substance use disorders also have preexisting
and concurrent impulsive, oppositional, self-injurious, and suicidal
symptoms or syndromes (627). Treatment should also address these
problems, with treatment of the substance use disorder(s) and coexisting
psychiatric symptoms occurring simultaneously.
In general, the range of treatment modalities used with adults
can be used with adolescents as well. These modalities include brief
interventions, motivational enhancement strategies, cognitive-behavioral
approaches, psychodynamic/interpersonal approaches (individual,
group, and family), self-help groups (628), and medications when
needed (629). Most adolescents are treated in outpatient settings,
and treatment is often delivered in a group therapy format. Although
research data establishing the efficacy of specific treatment modalities
for adolescent substance use disorders are sparse, program outcomes
for adolescents appear to be enhanced by the availability of treatment
that is developmentally appropriate and peer oriented and includes
educational, vocational, and recreational services. Corrective experiences
in family interaction should be part of the treatment plan (628). Family
therapy also appears to have benefit (241, 242, 630). Residential
facilities are very effective in reducing substance use, but gains
are lost when aftercare is not well coordinated (56).
The prevention of substance use and abuse is considered the
primary intervention for schools and clinicians (631–633).
At-risk children and adolescents include those with a substance-abusing
parent and those living under deprived conditions (i.e., neglect
and/or abuse). Educational programs describe the negative
consequences of substance use and teach drug refusal and harm-reduction
behavioral strategies. Life skills training is a substance use prevention
curriculum (634) that focuses on teaching youths the skills necessary to
avoid social pressures to experiment with smoking, drinking, and
drug use. In addition to showing efficacy in white middle-class
youth (634, 635), the effects of the life skills training approach
has also been demonstrated to be beneficial in African American
and Hispanic youth (636). Masterman and Kelly (637) noted that the
empirical literature suggests that universal prevention programs
may delay the onset of drinking among low-risk baseline abstainers
(i.e., individuals who are not drinking at the baseline assessment
and who would be predicted to be at low risk of developing an alcohol
use disorder on the basis of multiple risk factors); however, not
enough studies support the utility of such programs for at-risk
adolescents. Furthermore, they argue that motivational interviewing
within a harm-reduction framework is well suited to adolescents.
Interventions aimed at preventing smoking are similarly crucial,
given that smoking rates among adolescents continue to rise, despite
reductions in other age groups (638). Smoking in adolescents is
often a marker of psychiatric problems such as another substance use
disorder or depression. In adolescents who smoke, the motivation
to quit is often low; many of these adolescents are nicotine dependent
and will have difficulties stopping smoking without behavioral and
pharmacological support. There have been relatively few studies
of smoking cessation in adolescent smokers, and success rates with
interventions such as brief motivational enhancement, nicotine patch,
and bupropion appear to be very low, at approximately 20% by
the end of treatment (639–641).
Two common assumptions concerning adolescent substance use
that are unfounded should be mentioned. Supporting the findings
of a recent meta-analysis (506), a 16-year prospective, controlled
trial showed that the use of stimulant medication (e.g., methylphenidate)
in adolescence to treat ADHD does not lead to increased substance
use in adulthood (642). Furthermore, contrary to the common perception,
cannabis withdrawal is highly prevalent in adolescents (643).
Substance use disorders in elderly individuals are often undiagnosed
and undertreated (644, 645). Abuse of and dependence on prescribed
medications, particularly benzodiazepines, sedative-hypnotic medications,
and opioids, can contribute to excessive confusion and sedation
in elderly patients, poor adherence with prescribed treatment regimens,
and inadvertent overdose, particularly when these drugs are combined
with alcohol (646–648). In addition, alcohol use disorders,
whether an extension of a long-standing disorder or of later onset,
are a major problem among elderly individuals, particularly those
living alone (649–651). Alcohol-related cognitive impairment,
co-occurring depressive disorder, dementia, poststroke syndromes,
and other conditions are also common among elderly individuals and
may impair their ability to obtain or adhere to treatment for a
substance use disorder or other general medical or psychiatric disorder
(652).
Although rates of smoking decline with age (by 15%–20%),
elderly patients who do smoke should be encouraged to quit. Even
in older smokers, smoking cessation can lead to health improvements,
including improved quality and length of life. There are few published
studies of smoking cessation in the elderly; however, clinical experience
suggests that the use of NRT is a safe and effective option. However,
caution should be used when prescribing bupropion to elderly individuals
because of its potential hypertensive effects (653, 654). This agent
should be considered as a second-line agent, as controlled studies have
not been conducted in this population.
There is a paucity of empirical data on the treatment of substance
use disorders in the elderly population; it is generally accepted
that empirically supported treatments of adult substance use disorders
can be effectively applied to the treatment of elderly patients.
Some modifications, such as slowing the pace of therapy, placing
follow-up outreach calls, and providing patients with written information,
improve the effectiveness of some therapies. In a recent study of
250 elderly men screened for substance abuse from a VA outpatient population,
predictors of patient engagement in substance abuse treatment included
severity of substance use, co-occurrence of depression, healthy
cognitive status, and higher educational achievement (655). A large
multisite study (PRISM-E) has also shown that primary care patients
screening positive for a substance use disorder prefer to be treated within
the medical system, with integrated psychiatric and substance abuse
services, rather than to have facilitated referral to outside treatment
(31).
Studies of individuals with alcohol use disorders also suggest
that the needs of older adults may be different from those of younger
patients. Kofoed et al. (656) reported that VA patients age 54 years
or older who received specialized services for elderly patients
as part of a treatment program were four times more likely to complete
the program and remained in treatment longer than those who received
conventional services, although posttreatment relapse rates were
comparable in the two groups.
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7. Racial, ethnic,
and cultural factors
Current research suggests poorer prognoses for ethnic and
racial minorities in conventional treatment programs, although this
may be accounted for by socioeconomic group differences (657–659).
Although there is a paucity of research on the efficacy of culturally specific
programming, treatment services that are culturally sensitive and
address the special concerns of ethnic minority groups may improve
acceptance of, adherence to, and, ultimately, the outcome of treatment.
The training of staff to be sensitive to and incorporate culture-specific
beliefs about healing and recovery should be part of a comprehensive
treatment program that serves different minority and ethnic groups
(660). For example, Native Americans and Alaskans may have a greater
acceptance of treatment that incorporates the use of the Medicine
Wheel (661, 662). Still, clinical judgment in determining what cultural-based
modifications to treatment are appropriate is advised, because some
ethnic groups have large heterogeneity (e.g., Latino/ Latina [663]);
specialized cultural approaches (664) can be considered with a patient
to determine whether or not the approach would be perceived as useful.
In terms of nicotine dependence, African Americans and Hispanics
appear to be less likely to initiate smoking, tend to smoke in lower
amounts, and have increased cotinine levels (due to slower metabolism
of nicotine). When compared with whites, they appear less likely
to become dependent but have less success in smoking cessation efforts
(665–668). Recent studies suggest that the nicotine patch
(669) and bupropion (670) are safe and effective treatments for
African American smokers, but further study is needed.
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8. Gay/lesbian/bisexual/transgender
issues
Controversies in the literature exist about whether or not
substance use rates are elevated in homosexual and bisexual populations.
For example, earlier reports that lesbians are at higher risk than
heterosexual women for alcohol-related disorders (671) have not
been consistently replicated (672). Nonetheless, multiple studies
do indicate increased rates of drug use among gay and bisexual sexually
active men and lesbian women as compared with exclusively heterosexual
men and women, with a prominence of cannabis and nicotine dependence
for both homosexual men and lesbian women (673–675). In
one undergraduate college student population, a higher incidence
of drug use and smoking was found among gay and bisexual men and
lesbian women as compared with heterosexual men and women (676).
Among older gay, lesbian, and bisexual populations (ages 60–91
years), the incidence of alcohol abuse is greater for men than for
women (677). Methodological issues of population sampling may confound
interpretation of these findings. For example, in one community
with a high concentration of gay and bisexual men, few differences
were observed in drug use patterns among gay, bisexual, and heterosexual
men (678). Furthermore, demographic variables other than sexual
orientation influence the presence of substance abuse (679).
Because of concerns about increased risk and prevalence of
substance use disorders in gay, lesbian, and bisexual populations,
substance use disorder treatment programs frequently inquire about
an individual's sexual orientation and whether or not the
individual believes that his or her sexual orientation contributes
in any way to the substance use. Special therapeutic strategies
have been developed that target known regional associations between sexual
orientation and substance abuse, such as a Los Angeles program for
the treatment of male methamphetamine abusers who have sex with
other men (680, 681). The rationale for this program was the discovery
that this population has a high rate of HIV transmission. A similar
concern over the higher prevalence of smoking among adolescent and
adult gay, lesbian, and bisexual individuals has triggered the development
of prevention and cessation programs for these populations (682, 683). SAMHSA published a statement in 2001 concerning the need to
address substance abuse issues among gay, lesbian, bisexual, and
transgender populations (684).
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9. Family characteristics
Substance use disorders exact an enormous toll on family members.
High levels of interpersonal conflict, domestic violence, inadequate
parenting, child abuse and neglect, separation and divorce, financial
and legal difficulties, and substance-related general medical problems
(e.g., AIDS, tuberculosis), if present, can add to the family burden.
In addition, children reared in family environments in which other
family members abuse or are dependent on alcohol or other substances
are also at increased risk of physical or sexual abuse (685).
Families who have one or more members with a substance use
disorder often display a multigenerational pattern of transmission
of both a substance use disorder and other frequently associated
psychiatric disorders (e.g., ASPD, pathological gambling) (686, 687). The impact of maternal substance use on fetal development
and childhood cognitive and emotional adjustment, coupled with the
influence of genetically inherited risk factors (e.g., high genetic
loading for alcoholism in the male population) and negative role
models, plays a role in the development of substance use disorders
across generational lines (688).
The substantial burden that having one or more members with
a substance use disorder imposes on families and the impact of family
interactions in perpetuating or ameliorating these problems affect
the initiation of, perpetuation of, and patient's recovery
from the substance use disorder; the patient's motivation
and ability to adhere to treatment; and the patient's clinical
course and outcome. These relationships, combined with the high
prevalence of substance use disorders, co-occurring general medical
and psychiatric disorders, psychosocial disability, and family burden
make family screening and interventions extremely important (232, 236, 689, 690).
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10. Social milieu
and living environment
The patient's overall social milieu has an important
impact on the development of and recovery from a substance use disorder.
The social milieu shapes attitudes about the appropriate context
for substance use (e.g., the difference between social drinking
on family occasions and recreational drinking to achieve intoxication).
Role models among one's family or peers influence the social
and psychological context for substance use, the choice of substance,
and the degree of control exerted over substance-using behaviors.
Once a pattern of dependence or abuse has developed, an individual's
motivation and ability to adhere to treatment are influenced by
the degree of support within his or her immediate peer group and
social environment. Poor outcome is predicted by continued involvement
with substance-using peer groups or family members as well as by
residence in an environment in which substances are readily available.
Addressing these issues is an important component of any treatment
plan. Patients with high levels of psychosocial and environmental
stressors need correspondingly high levels of community-based support
or, in some cases, temporary relief from these stressors through
treatment in a residential setting until the patient is able to
develop specific relapse prevention strategies that can be applied in
a community setting. Sexually active individuals should be educated
about the prevalence and prevention of HIV infection and other sexually
transmitted diseases (691).
Socioeconomic status may also play a role in the initiation
and cessation of substance use. For example, smokers with lower
education level, wages, and socioeconomic status are more likely
to initiate smoking and less likely to quit; this may be due to
less support for attempts to quit and less access to smoking cessation
services. (692, 693).
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H. Legal and Confidentiality
Issues
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1. Effect of legal
pressure on treatment participation and outcome
Many patients with substance use disorders seek treatment
in response to pressure from family members, employers, legal authorities,
or other sources. Although being internally motivated for treatment
is often regarded as a good prognostic sign, outcome studies of
patients in therapeutic communities have shown that individuals
who enter treatment under legal compulsion (e.g., as a condition
of probation, to avoid incarceration) stay longer and do as well
as comparable patients who enter treatment voluntarily (694, 695).
The use of the opiate antagonist naltrexone has produced higher
rates of adherence to court-mandated treatment by patients and physicians
or other professionals who are at risk of losing their professional
licenses should they fail to comply. Similar findings have been
reported for professionals being treated for substance use disorders
by means of contingency contracting approaches in which the contingency
for nonadherence with treatment is being reported to a professional
board of registration (696).
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2. Confidentiality
and reporting of treatment information
To protect patients' privacy and encourage their
entry into treatment, federal law and regulations mandate strict
confidentiality for information about patients being treated for substance
use disorders (i.e., 42 U.S.C. Sections 290 dd-3 and ee-3; 42 C.F.R.
Part 2). Disclosure of information from treatment records is prohibited
unless the patient has given written consent, the disclosure is
in response to a medical emergency, or there is a court order authorizing
disclosure. Other times when patient confidentiality may be attenuated
include disclosure needed to protect or warn third parties of potential
harm by the patient, disclosure in response to a crime committed
at the treatment program or against program staff, reporting of
suspected child abuse or neglect, or, depending on the requirements
of the local jurisdiction, reporting of suspected abuse of elderly
individuals. Consequently, psychiatrists should be familiar with
local and state reporting laws concerning the possible abuse and
neglect of children, other dependents, or elderly individuals who
may be at risk in the families of substance users.
Federal law generally does not make specific reference to
the confidentiality of information pertaining to the HIV/AIDS
status of a patient in substance abuse treatment, but there are
many different state laws restricting disclosure of such status.
The federal Health Insurance Portability and Accountability Act
of 1996 has been particularly prominent in protecting the privacy
of patients with a psychiatric disorder (697). Psychiatric disorders commonly
co-occur with substance use disorders, and these patients are "doubly
protected" by law.
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3. Legal requirements
for pharmacotherapy with opioids
Federal and state regulations govern the use of methadone,
LAAM, and buprenorphine, the three opioids approved by the FDA for
the treatment of opioid dependence. Programs that use these agents
to treat opioid-dependent patients are registered with and accredited by
the Center for Substance Abuse Treatment. The center holds opioid
agonist treatment programs to a variety of accreditation standards
that regulate issues such as admissions, record keeping, and the
frequency of drug testing. In addition, individual states may also impose
stricter licensing criteria for these programs.
In an effort to expand access beyond the highly regulated
opioid agonist treatment programs, Congress passed the Drug Addiction
Treatment Act of 2000, which allows "qualified physicians" in
office-based practices to prescribe FDA-approved schedule III, IV,
and V medications for the detoxification and maintenance of opioid
dependence. Currently, sublingual buprenorphine and sublingual buprenorphine/naloxone
are the only agents approved by the FDA for this purpose. Most physicians
qualify by completing 8 hours of formal training and obtaining a
special U.S. Drug Enforcement Agency number ("x" number). To
obtain this number, physicians must have the capacity to refer patients
for appropriate counseling and other ancillary services. Once qualified,
physicians may treat patients in an individual or group practice
with sublingual buprenorphine or sublingual buprenorphine/naloxone.
As with all opioid agonist therapies, strict documentation of informed
consent, qualification of the patient as being dependent on opioids
with a history of relapse or medical risk, ongoing monitoring of
efficacy, and evidence of abstinence or substance use through urine
toxicology testing are required for safe prescribing. Physicians
should also document the protection of children from accidental
access to medication.
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III. Treatment of
Nicotine Dependence
Smoking is common among individuals with other substance use
and psychiatric disorders (698, 699). Although most psychiatrists
do not offer comprehensive nicotine dependence treatment, the multiple
negative health effects of tobacco use make it important for clinicians
to identify tobacco smokers and smokeless tobacco users, provide
motivational interventions to encourage patients to quit tobacco
use, and be familiar with medications and psychosocial interventions
that are effective in treating nicotine dependence. Although there
have been several recent controlled studies of smoking cessation
treatments among psychiatric patients (414, 700–705), most
of these studies have been of limited sample size and primarily
involved cohorts of patients with schizophrenia. Thus, much of what
is recommended in this section is similar to other recommendations
for psychiatric patients who smoke (173, 414, 698, 705) as well
as being consistent with guidelines from the U.S. Public Health
Service (706) for the treatment of smokers who do not have a current
psychiatric disorder. It is also important to note that the treatment
of nicotine dependence differs from that of other drug dependencies
in the following ways: 1) treatment commonly uses pharmacotherapies
(e.g., NRT, bupropion), with varying levels of behavioral treatment
given to those willing to receive it; 2) a specific "quit
date" when all tobacco use is to cease is set; 3) a nicotine-dependent
individual generally does not experience substantial social/occupational
dysfunction due to tobacco use; 4) there is less of a need for family
involvement in such treatment; and 5) effective over-the-counter
medication treatments are available for treating this dependence.
In addition to the general aspects of assessment outlined
in Section II.B, the patient's current level of tobacco
use (e.g., number of cigarettes per day) and degree of nicotine
dependence also need to be determined, because highly nicotine-dependent
individuals are more likely to need more intensive therapy, especially
pharmacotherapy. The Fagerström Test for Nicotine Dependence
(Table 4) is widely used in treatment studies and has proven reliability
and validity (707–710).
A score of <3 on this scale indicates that an individual
has very low or no nicotine dependence, whereas a score of 6 suggests that an individual
is highly dependent on nicotine (708). This scale can also predict
which smokers are likely to quit smoking and which may benefit from
high-dose NRT (described in Section III.E.1). Nicotine dependence
in smokeless tobacco users is common, and attempts have been made
to measure dependence levels in this group as well (712).
Several other markers of nicotine dependence have been proposed,
such as number of cigarettes per day, time to first cigarette (an
item on the Fagerström test), cotinine levels, degree of
withdrawal on last attempt, and number of unsuccessful attempts
to quit. However, with the possible exception of time to first cigarette
(713), these markers have yet to be shown to have significant treatment
utility. DSM criteria for substance dependence (Table 2) also appear
to be reliable and have prospective validity in diagnosing nicotine
dependence (714).
As indicators of use, nicotine and cotinine levels can be
measured in blood, saliva, and urine (105). Nicotine levels can
reflect tobacco use over the last few hours, whereas the level of
cotinine, a metabolite of nicotine, is sensitive to tobacco use
in the last 7 days and offers a better measure of total daily nicotine
exposure (105). It has been proposed that the measurement of cotinine
levels be used to help guide nicotine replacement, but the utility of
this strategy has not been well tested (173). An individual's
carbon monoxide level is usually measured by breath and reflects
smoking only over the last few hours (105). It has been suggested
that the measurement of carbon monoxide is a means of motivating
a patient to cease tobacco use or reinforcing abstinence (715),
but the efficacy of this is unclear. The major benefit to using
carbon monoxide levels as a marker is that it is easily measured and
can be used to verify cessation of tobacco use when patients are
using an NRT (105). Because smokers in nontreatment (or minimal
treatment) settings are usually truthful about their smoking status
and the number of cigarettes smoked per day (716), the described
measures are not necessary for evaluating smoking cessation, although
they show promise as helpful assessments.
Because 70% of smokers make more than one attempt
to stop smoking (602), it is important and useful to inquire about
and assess patient perceptions about prior attempts and past treatment
adequacy. In addition to determining the patient's reasons
for previous attempts to quit tobacco use and the amount of time
he or she remained abstinent, it is important to assess the perceived
cause of relapse. For example, was the relapse due to uncontrolled
withdrawal symptoms, environmental stressors, alcohol use, negative
or positive mood, psychiatric instability, or being around other
smokers or tobacco users? Were there factors (e.g., fatigue, life
disappointments, family or other social stressors) that undermined
abstinence? What did the patient learn from prior failures? Past
efforts to quit may also influence a patient's readiness
and motivation to try quitting again. Thus, it is also important
to understand the changes that a patient thinks need to occur before
he or she can make another attempt to quit tobacco use, his or her
fears about quitting, and the barriers to another attempt to quit.
For patients who have returned to tobacco use despite past
efforts at treatment, a first consideration is the adequacy of prior
treatment. For example: What was the duration of therapy? How many
sessions of behavioral therapy were attended? What was the quality
of the behavioral treatment in the last attempt to quit? What were
the doses of gum or patch used? What was the level of adherence
with the psychosocial or somatic therapy? It is also helpful to
determine the patient's satisfaction with prior treatments.
For example, did he or she believe that treatment was helpful? Did
treatment experiences change his or her expectations of future treatment
or its outcome?
The assessment of psychiatric patients in terms of cessation
of tobacco use focuses on a number of other key points:
- Is the patient motivated
to quit using tobacco in the next month?
- Are there any psychiatric reasons for concern about
whether this is the best time for cessation? Is the patient about
to undergo a new therapy? Is the patient presently in crisis? Is there
a problem that is so pressing that time is better spent on this
problem than on cessation of tobacco use?
- What is the likelihood that cessation would worsen the
non-nicotine-related psychiatric disorder?
- Are there any signs or symptoms of other undiagnosed
psychiatric or substance use disorders that might interfere with
efforts to quit tobacco use?
- What is the patient's ability to mobilize coping
skills to deal with cessation?
- What is the tobacco use status (e.g., never smoked,
former smoker, current smoker) of others in the patient's
household and among the patient's close friends?
- What are the patient's treatment preferences
and the basis for these preferences?
A discussion of the impact of these factors on the approach
to treatment can be found in Section III.D, below.
With the exception of patients hospitalized for other reasons,
treatment of nicotine dependence occurs on an outpatient basis.
However, an inpatient model for smoking cessation has been described
(717) and appears to produce high cessation rates, especially given
the level of nicotine dependence among smokers who enroll. There
are no controlled trials that substantiate this at the current time.
Regardless of the specific setting, treatment best occurs
in a system that encourages cessation (33). This may be especially
important to achieve on psychiatric inpatient units, as discussed
below in Section III.G. The psychiatrist should also consider maintaining
a smoke-free work site (33, 34).
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D. General Approach
to Treatment
As with treating other substance use disorders, the general
goals in treating nicotine dependence include motivating and engaging
an individual in treatment to reduce or preferably cease using tobacco.
However, the general approach to treatment of nicotine dependence
will depend on a number of factors, including the patient's
psychiatric status, level of nicotine dependence, past treatment
and efforts at quitting tobacco use, and current motivation for
reducing or quitting tobacco use. This section discusses the general
approach to nicotine dependence treatment; specific aspects of the
pharmacotherapy and psychosocial treatments of nicotine dependence
are discussed in Sections III.E and III.F, respectively.
Meta-analyses have found that the general techniques described
below increase rates of quitting by a factor of 1.5–2.0
(718–721). Descriptive reviews of the skills and techniques critical
to smoking interventions have also been published (33, 172, 722–728).
Research shows that 98% of tobacco use involves cigarettes,
and most of the studies of treatments for nicotine dependence and
smoking cessation have been in cigarette smokers (602). The available
evidence suggests that other forms of tobacco use (e.g., pipe, cigars, smokeless
tobacco) are becoming increasingly common (692). Although studies
of treatment interventions are limited, pipe and cigar use are associated
with higher rates of nicotine dependence because of their higher
nicotine content. Thus, these other forms of nicotine use should
also be taken into consideration in the assessment and treatment
planning process.
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1. Establishing and
maintaining a therapeutic framework and alliance
Nicotine dependence is a chronic relapsing disorder; most
smokers require five to seven attempts before they finally quit
for good (729). Many patients do not realize that several attempts
are often needed to stop smoking, and they will need to be remotivated
to attempt to quit after a previous failure (33). Because of this,
it is important to establish a therapeutic relationship so that
the patient will accept treatment for subsequent attempts to quit,
if necessary (33).
Clinician advice for individuals attempting to quit tobacco
use is best given in a nonjudgmental, empathic, and supportive manner
(32, 33). No studies have been conducted to test whether confrontational
interventions applied in treating other substance use disorders are
useful with nicotine dependence. In patients with a present or past
psychiatric disorder, it is important to convey the message that
simply having a psychiatric disorder is not a reason not to make
a quit attempt (725, 730).
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2. Increasing readiness
and motivation for smoking cessation
A patient's current motivation will determine what
strategies should be used to enhance and support his or her readiness
and attempts to quit smoking. Because many psychiatric patients
are ambivalent about stopping smoking or are not ready to attempt
to quit (731–733), nicotine dependence treatment will most
often consist of enhancing their motivation and dealing with anticipated
barriers to cessation (33).
Brief advice from a physician (using protocols similar to
those recommended by the National Cancer Institute) to stop smoking
typically doubles quit rates, from approximately 5% to
10% (718–721, 734, 735). Advice from nonphysicians
is also effective (718, 721), and advice from multiple sources is
more effective (718, 721). Thus, clear direct advice from the psychiatrist
and other psychiatric personnel (e.g., nurses, social workers) to
stop smoking is an essential initial therapeutic step that may increase
patient readiness and motivation to try other therapies as needed.
Stages-of-change approaches and motivational enhancement models
(32, 736) may help formalize interventions to enhance a patient's
motivation. Such interventions will generally include providing
information and feedback on the risks of smoking and reasons for
quitting that are specific to the individual patient. The most common
reasons for trying to stop smoking are to improve health and respond
to social pressure (737). Revisiting the issue of smoking cessation
at periodic intervals, especially with the occurrence of smoking-related medical
conditions (e.g., bronchitis) or other special situations (e.g.,
pregnancy, living with a child with asthma), can sometimes motivate
smokers to consider quitting (737–740). Documenting smoking
status (as well as concurrent alcohol or other drug use) in the
medical record may help facilitate such a follow-up.
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3. Overcoming barriers
to smoking cessation
Patients who smoke may express negative feelings or fears
related to quitting that may serve as a barrier to their smoking
cessation. The most common concerns are fear of weight gain, fear
of withdrawal, and fear of failure (737). Women frequently cite
the fear of weight gain or actual weight gain after quitting smoking
as negative reinforcers contributing to smoking relapse. The exacerbation
of psychiatric symptoms is likely to be an additional barrier for
psychiatric patients (32). There is little evidence that smoking
cessation can exacerbate psychiatric symptoms in patients diagnosed
with schizophrenia or major depression whose symptoms are stabilized.
However, any patient fears about withdrawal symptoms or a worsening
of psychiatric problems may be dealt with by problem-solving approaches,
increased monitoring by the clinician, behavioral therapy, or treatment
with NRT, bupropion, or both.
Patients who smoke may also be uninformed and demoralized
about their inability to change or may be defensive and resistant
to change. Thus, it may be helpful for a clinician to clarify and
legitimize patients' feelings, explore the reasons for
their smoking, and offer expressions of support and respect. If
feelings of demoralization are uncovered, they can be addressed
by informing the patient that even smokers who are very committed
to quitting may make several attempts to quit before they finally
succeed. Patients who become chronically ambivalent about quitting
may benefit from encouragement to take small steps toward their
goal of quitting, such as reducing the number of cigarettes they
smoke or trying to quit for just 24 hours. The psychiatrist supports
self-efficacy by identifying and praising past behavioral change
and encouraging the use of strategies that were effective in the
past.
Smoking by others in the household and close friends may also
present a barrier to treatment. Whether and how others in the household
and friends have supported or undermined a patient's prior
attempts to quit should be evaluated. Conversely, social support
is a major predictor of cessation (741). If others in the household
are current smokers, it is useful to determine their willingness
to quit at the same time as the patient or not to smoke in front of
the patient.
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4. Eliciting patient
preferences about treatment
Patients' treatment preferences and the reasons for
those preferences should be elicited and considered when developing
a treatment plan. For example, some patients may prefer to stop
smoking on a certain date or may have strong likes or dislikes about
pharmacotherapy, group therapy, or individual therapy. These factors
will be important in setting a specific quit date as well as enhancing
the patient's adherence to the treatment plan.
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5. Determining timing
of smoking cessation
When and how cessation advice is best delivered must be determined
by the patient's status; for example, smoking cessation
is not likely to be successful when the patient is in crisis. The
best time for cessation would appear to be when the patient is psychiatrically stable,
there are no recent or planned changes in medications, and no urgent
problems take precedence (730). On the other hand, admission to
a smoke-free inpatient unit or integrating smoking cessation into
other lifestyle changes that are a part of ongoing psychiatric treatment
(e.g., during cessation of alcohol use) can sometimes motivate a
patient to quit smoking. More immediate cessation is indicated if
the patient has recently been diagnosed with a smoking-related medical
disorder; individuals with such disorders generally have high success
rates for quitting (737, 740). Whenever a smoking quit date is postponed,
it is helpful to list smoking cessation as a goal on the master
psychiatric treatment plan so that it can be addressed at a later
time.
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6. Determining whether
smoking cessation will be abrupt versus gradual
Most patients attempt and most clinicians recommend abrupt
cessation of smoking rather than gradual reduction (742). Previous
thinking has held that gradual reduction is less successful because
patients appear to have difficulty achieving further reductions
once they have cut down smoking to 5–10 cigarettes per
day (173). On the other hand, most of the scientific data available
suggest no difference in the outcomes of abrupt versus gradual cessation
(173, 718, 719, 743); thus, patient preference to follow a gradual
reduction strategy should be respected. A gradual approach may also
be considered if the patient is historically uninterested or unable
to quit smoking, as a significant and sustained reduction in smoking might
still be achievable. Whether reductions in smoking are related to
decreasing risk for smoking-related medical illnesses has not been
clearly established (744, 745).
Once the above factors have been addressed and the patient
agrees to stop smoking, a specific quit date is set and a concrete
discussion of cessation procedures occurs. In addition, the psychiatrist
may give the patient written materials that provide suggestions
for succeeding in quitting. Even if a gradual approach to smoking
cessation is chosen, patients should generally be advised to set
a date by which they will completely stop smoking and that they
should not use NRT until they have stopped smoking. Because many
patients relapse within the first few days of smoking cessation
(746), it is important for the psychiatrist or the psychiatrist's
staff to call or see the patient in the first 1–3 days
after the quit date.
If the patient is not ready to make a commitment to a quit
date, the psychiatrist should plan to readdress smoking at a later
date, encourage the patient to reconsider, and offer to help if
the patient changes his or her mind. In addition, the psychiatrist
may give the patient written materials that are intended to motivate
the patient to make a quit attempt or that give tips on how to successfully
quit.
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8. Developing a plan
of psychosocial and pharmacological treatment
In the general population,
most smokers quit on their own or with minimal treatment (747);
for those who are unable to stop with minimal intervention, many
algorithms and guidelines recommend a stepped-care approach, with
minimal intervention early on and more intensive intervention later
in the course of treatment (140, 172, 748–750). At the same
time, most smokers who quit on their own require several attempts
before they succeed (750); thus any success later in the algorithm
cannot be attributed to the specific treatment being given at that
point. Just as important, early cessation of smoking can prevent much
of the devastating consequences of smoking (751); thus, delaying
delivery of a treatment known to be effective could allow a serious,
irreversible consequence of smoking (e.g., acute myocardial infarction,
lung cancer) to develop. Consequently, the availability of effective
treatments for smoking cessation as well as the rarity of significant
adverse effects of those treatments suggests that pharmacotherapy
be offered to all patients who wish to stop smoking. Combining psychosocial
and medication treatment generally produces the best outcomes; however,
medications are effective even when no psychosocial treatment is provided.
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b) Monitoring clinical
status
After the first follow-up 1–3 days after the quit
date (see Section III.D.7), additional follow-ups may be scheduled,
depending on the patient's perceived need, history of cessation, and
psychiatric history. Follow-up visits may also be needed to assess
a medication blood level that might increase with cessation. Follow-up
visits may also be needed to monitor side effects or plan tapering
of antismoking medications.
At follow-up, the psychiatrist assesses whether the patient
has smoked and, if so, the number of cigarettes smoked per day;
the severity of the patient's withdrawal symptoms; the
onset of any psychiatric symptoms; the patient's use of
alcohol or other drugs; how the patient dealt with situations in
which he or she felt a strong urge to smoke; medication side effects;
and other relevant issues and then tailors treatment accordingly
(33). Most but not all studies suggest that brief follow-ups (including
telephone calls) increase quit rates (720, 721, 752–754).
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(1) Identifying symptoms of withdrawal
Nicotine withdrawal symptoms typically begin a few hours after
the patient has ceased smoking and include dysphoric or depressed
mood; insomnia; irritability, frustration or anger; anxiety; difficulty
concentrating; restlessness; decreased heart rate; and increased
appetite or weight gain. Although most symptoms peak 24–48
hours after cessation, they last an average of 4 weeks, with hunger
and craving for tobacco lasting 6 months or more in some individuals
(755). The duration of nicotine withdrawal symptoms may be a more
important determinant of smoking relapse than the severity of the
symptoms (756). Smoking cessation can cause physiological problems
such as slowing of electroencephalographic activity in the awake
and sleep state, decreases in cortisol and catecholamine levels,
and a decline in the patient's metabolic rate (757). The
mean heart rate decline is about 8 bpm, and the mean weight gain
is 2–3 kg (757).
Nicotine withdrawal can occur in association with all forms
of tobacco use (cigarettes, chewing tobacco, snuff, pipes, cigars)
as well as with NRTs (755, 757). The ability of these products to
induce or maintain dependence and withdrawal increases with the
rapidity of the absorption of nicotine, the nicotine dose, and the
availability of the product (758). Consequently, although symptom
severity varies among patients (757), withdrawal is usually most
severe with cigarette abstinence compared with abstinence from other
forms of tobacco and nicotine medications (755, 757, 759).
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(2) Identifying exacerbations of psychiatric symptoms
Patients with current or past psychiatric symptoms or disorders
need particularly close monitoring in the first 14 days after smoking
cessation because nicotine withdrawal symptoms such as anxiety,
depression, increased rapid eye movement sleep, insomnia, irritability,
restlessness, and weight gain can mimic, disguise, or aggravate
the symptoms of other psychiatric disorders or side effects of medications.
For example, when an alcohol-dependent individual who is also nicotine
dependent is admitted to a smoke-free ward for alcohol detoxification,
his or her anxiety, depression, difficulty concentrating, insomnia,
irritability, and restlessness could be due to or aggravated by
nicotine withdrawal. Although more studies support concurrent attempts
to quit smoking and drinking, there is one study that suggests that
relapse to alcohol is more likely with concurrent smoking cessation
(38). There have been several prospective studies (760, 761) that
have examined whether smoking cessation can exacerbate depressive
(762–766) or psychotic (414, 702, 703, 767) symptoms in patients
with major depression and schizophrenia, respectively; most of the
available evidence suggests that this risk is low when patients' psychiatric
symptoms are stabilized prior to the cessation attempt.
A patient's psychiatric status should also be monitored
because blood levels of some psychiatric medications (e.g., those
metabolized by the CYP 1A2 microsomal system, including clozapine,
fluphenazine, haloperidol, oxazepam, desmethyldiazepam, clomipramine,
nortriptyline, imipramine, desipramine, doxepin, and propranolol)
may increase substantially within 3–6 weeks when patients
taking such medications stop smoking, and these increases could
worsen side effects or cause toxicity (414, 698, 760, 768, 769).
This effect appears to be due not to nicotine but rather to the
effects of benzopyrenes (tobacco carcinogens) and related compounds
on the P450 system.
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9. Providing education
and enhancing adherence
Many patients do not realize their smoking may be a form of
nicotine dependence (770). Key points to convey to patients include
the following: 1) most smokers try to quit multiple times before
they finally succeed, but with persistence, half of all smokers
quit; 2) most smokers fail early on, but if the smoker is able to
remain abstinent for 3 months, relapse is unlikely; 3) nicotine
withdrawal can be relieved with NRT; 4) true withdrawal symptoms generally
last 4 weeks or longer and may include dysphoric or depressed mood,
insomnia, irritability, frustration or anger, anxiety, difficulty
concentrating, restlessness, decreased heart rate, increased appetite,
or weight gain (33).
To support a patient's adherence to treatment, it
is important to deal with the patient's concerns about
weight gain. Even though the health benefits of stopping smoking
clearly outweigh the health risks of weight gain (771), fear of
weight gain is common and is a major deterrent to smoking cessation,
especially in women (772, 773). On average, smokers weigh 2–3
kg less than individuals who have never smoked, and when smokers
stop smoking, they gain weight until they are similar in weight
to those who have never smoked (771). Most smokers gain weight over
the first few months after quitting smoking, but many later lose
much or all of this weight. Women who are already trying to decrease
their weight gain the most (773). However, smoking cessation-related
weight gain does not cause a relapse to smoking (755). In fact,
a concentrated effort to control weight gain by dieting during abstinence
increases, not decreases, the chances of a relapse to smoking (774, 775). This may be because attempting to quit smoking and dieting
at the same time is just too difficult. Clinicians can recommend
that patients increase their physical activity and learn healthy
eating strategies rather than diet or convince patients to tolerate
a moderate amount of weight gain over the first 3 months after smoking
cessation and work on losing weight later (775). Nicotine gum, but
not the nicotine patch, appears to delay weight gain and could be
used to delay attempts to control weight until a relapse to smoking
is less likely (776).
Alcohol use is a risk factor in most studies for relapsing
to smoking (777); thus, it is recommended that patients who are
attempting to quit smoking either diminish their alcohol intake
or abstain from alcohol. Caffeine use typically does not change
with smoking cessation (755), and it is unclear whether caffeine
use is a risk factor for relapse (769). Smoking increases the metabolism
of caffeine, and smoking cessation increases caffeine levels by 50%–60% (778).
Because many of the symptoms of caffeine intoxication and nicotine withdrawal
overlap (e.g., anxiety, insomnia, restlessness), reducing caffeine
intake after smoking cessation might be helpful; however, the one
study to test this hypothesis found caffeine does not increase the
severity of tobacco withdrawal (778). In addition, abruptly stopping
caffeine could induce a withdrawal syndrome of its own (779). In
summary, with this contradictory evidence, patient preferences on
whether to change caffeine intake should be respected.
Because smoking even one cigarette during a cessation attempt
often portends a full-blown relapse (780), reports of any slips
should prompt immediate planning around changes in behavioral therapy
(e.g., discuss ways to avoid or cope with the situation that led
to the slip) or changes in pharmacotherapy (e.g., increased dose,
change in medication). If the patient has fully relapsed, the psychiatrist
should praise the patient for even limited success. The patient
and psychiatrist should then discuss what was learned with this
quit attempt and when the patient would like to think about trying
again. Most patients who relapse continue to be interested in stopping
smoking; thus, the psychiatrist should discuss setting a time to reconsider
another cessation attempt.
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10. Determining approaches
for patients who do not respond to initial treatment
When a patient does not respond to a trial of a known effective
formal therapy (e.g., behavioral therapy, NRT, bupropion, a combination
of these therapies), it is first important to determine if the treatment
was adequately or inadequately implemented. If inadequately implemented,
the therapy may be repeated with changes to ensure the fidelity
to therapeutic steps, treatment adherence, and adequacy of treatment
dose and duration.
If the treatment was both appropriate and adequately implemented,
rescreening the patient for other co-occurring disorders is indicated,
as other unrecognized substance use or psychiatric disorders can
interfere with smoking cessation (698, 760, 781). The psychiatrist should
also attempt to determine whether the relapse was related to withdrawal
symptoms or other causes. If the patient has not previously been
treated with NRT and the prior relapse appeared to be caused by
withdrawal symptomatology, NRT is appropriate. If the patient has
been adequately treated with NRT, the psychiatrist may consider
bupropion and/or a different formulation or dose of NRT.
If these approaches are also ineffective, the use of clonidine or
nortriptyline could be considered.
Other NRT delivery systems can also be considered. Although
its side effects can limit its acceptability to some patients, nicotine
nasal spray produces a more bolus-like effect that might better
relieve withdrawal symptoms and craving (782), especially in heavy smokers
who report that they relapsed to smoking both for withdrawal relief
and for the positive effects of nicotine and tobacco (e.g., liking,
satisfaction). A nicotine inhaler has the added advantage of replicating
the hand-to-mouth motor acts associated with smoking, which may
further support its utility. A strategy of initially using nicotine
nasal spray and then switching to a nicotine patch or concomitantly
using nicotine nasal spray and patch has been proposed and received
some empirical support from controlled studies (782a, 782b, 1563).
The combination of a patch with a faster-acting NRT such as gum,
lozenge, spray, or inhaler may have some rationale, as the patch
provides a steady level of nicotine for withdrawal relief and the
faster delivery systems address the positive aspects of smoking
(satisfaction and liking).
If the patient has relapsed because of a stressful life event
and has not previously been treated with behavioral therapy, this
type of therapy should be considered. If the patient has already
had behavioral therapy, two choices are available: 1) more intensive
behavioral therapy or 2) behavioral therapy within a different content
or format (e.g., group therapy, individual therapy, combined individual
and group therapy, involvement of family members). Whether these
treatments are effective for those who have not responded to prior
behavioral therapy has not been studied. Sometimes it is difficult
to distinguish withdrawal versus nonwithdrawal causes of relapse.
Under such circumstances, the patient may be a candidate for combined
pharmacological and behavioral therapy (783, 784).
The results of three small controlled studies of acupuncture
are promising (785–787), but due to methodological limitations,
they do not justify the use of acupuncture for treating nicotine
dependence either alone or in combination with other treatments.
Furthermore, a meta-analysis of 22 controlled studies suggests acupuncture
lacks efficacy in promoting smoking cessation (788).
When the treating psychiatrist does not have the knowledge
necessary to implement the treatments outlined herein, or if the
strategies are administered and the patient is not able to quit
smoking, the psychiatrist should consider referring the patient
to someone who specializes in treating nicotine dependence.
+
1. Nicotine replacement
therapies
NRTs can be used as a first-line treatment approach for any
individual who wishes to stop smoking. At present, there are five
FDA-approved forms of NRT: patch, gum, lozenge, nasal spray, and
inhaler. Because all are effective in alleviating withdrawal symptoms
(789) and reducing smoking (790) in men and in women (791, 792),
the choice of a specific NRT typically depends on patient preference
and the NRT's route of administration and side effect profile
(793). It is unclear what adjustments to NRTs are needed for pipe
and cigar users; probably these therapies should be implemented
according to the patient's nicotine dependence level as
measured by the Fagerström Test (794). Using a combination
of NRTs (790) or combining NRT with bupropion (795) or psychosocial
therapies (790) may improve outcome.
The optimal duration of NRT is debatable (693). Although some
individuals appear to require long-term use of NRT (e.g., 6 months), almost all
eventually stop using such agents, and the development of dependence
on these agents is rare (796, 797). Thus, patient preference should
be the major determinant for the duration of an NRT.
Of the NRTs, many individuals find it easier to adhere to
nicotine patch therapy. Typically, nicotine patch therapy will begin
with a high-dose patch (21 or 22 mg); however, patients who smoke
<15 cigarettes per day are candidates for starting with an intermediate-dose
patch (e.g., 11 or 14 mg) or for using another form of NRT (798).
Whether the 24- or 16-hour patch is better is debatable (71, 798).
The 24-hour patch may better relieve morning craving but appears
to cause insomnia in some patients (799, 800). Other common side effects
are skin irritation (which can be diminished by rotating patch placement
sites), nausea, and vivid dreams; however, patients usually develop
tolerance to these side effects (790, 801). The recommended duration
of nicotine patch therapy is 6–12 weeks, with a tapering
of the patch dose over that period; longer durations of patch therapy
have not been found to be more effective (790).
When nicotine gum or lozenges are used, scheduled dosing (e.g.,
one 2-mg lozenge or piece of gum every hour) rather than ad libitum
dosing is often best. The 4-mg dose is recommended for heavy smokers
(>25 cigarettes/day) or more nicotine-dependent smokers (790, 802, 803). The dose of nicotine replacement can be tapered over
6–12 weeks by decreasing the gum or lozenge dose (i.e.,
from 4 to 2 mg) and/or increasing the time between doses.
Patients also benefit from receiving instructions about proper use
of these NRTs. With nicotine gum, patients should be instructed
to chew one piece of gum very slowly until a slight tingling or
distinctive taste is noted, at which time the gum should be placed ("parked")
between the cheek and gum until the taste or tingling is almost
gone. This process is then repeated over about 30 minutes for each
piece of gum. Nicotine lozenges should be sucked on rather than
bitten or chewed. Typical side effects of lozenges are minor but include
nausea, heartburn, and mild throat or mouth irritation; side effects
of the gum are jaw soreness or difficulty chewing (802, 804). In
addition, the lozenge contains phenylalanine and should not be used
by individuals with a history of phenylketonuria. With both the lozenge
and the gum, it is important to avoid beverages other than water
immediately before or during NRT use because associated pH changes
can blunt nicotine absorption (804a).
Nicotine nasal spray and vapor inhaler systems provide faster
delivery of nicotine than gum or lozenges, but still deliver nicotine
more slowly and with lower peak nicotine levels than cigarettes.
Nicotine nasal sprays produce droplets that average 1 mg per administration,
and patients administer the spray to each nostril every 1–2
hours. Nicotine vapor inhalers are cartridges of nicotine that are
placed inside hollow cigarette-like plastic rods and produce a nicotine
vapor (0.013 mg/puff) when smokers puff on them (805, 806).
The recommended dose is 6–16 cartridges daily, with the
inhaler being used ad libitum for about 12 weeks. Short-term side
effects from nicotine nasal spray include nasal and throat irritation,
rhinitis, sneezing, coughing, and watering eyes in up to 75% of
users (807–809), and nicotine inhaler use is most often
associated with throat irritation or coughing in up to 50% of
users (806, 810). When compared with other forms of NRTs, the nasal
spray and inhaler may have somewhat higher rates of continued use
for periods >6 months (782, 796, 811).
The antidepressant agent bupropion in the sustained-release
formulation is a first-line pharmacological treatment for nicotine-dependent
smokers who want to quit smoking. Bupropion appears to have comparable
tolerability and effectiveness to NRTs (158–160, 795, 812)
and is equally beneficial in men and women (813). The target dosage
for individuals with nicotine dependence is 300 mg/day.
The medication is initiated at 150 mg/day 7 days prior
to the target quit date; after 3–4 days, dosing is increased
to 300 mg/day (150 mg b.i.d.). Bupropion can also be used
in combination with an NRT, although the evidence is mixed on the
extent to which this improves outcomes (795).
The primary side effects associated with bupropion are headache,
jitteriness, insomnia, and gastrointestinal symptoms (795). Caution
is needed when prescribing bupropion to individuals with a history
of seizures of any etiology, as seizures have also been observed with
bupropion treatment. The use of bupropion, especially the short-acting
preparation, is also discouraged in patients with a past, and particularly
a current, diagnosis of an eating disorder (i.e., anorexia nervosa
or bulimia nervosa) because of higher rates of seizures observed
in initial studies of the medication (161). In other individuals,
the rate of de novo seizures is low (<0.5%), and such
seizures are predominantly observed when daily dosing exceeds 450
mg/day (795).
There is also support for the use of nortriptyline and clonidine
as treatments for nicotine dependence; however, given the number
of other available treatments for which results are well validated,
these should be viewed as second-line therapies. Nortriptyline may
be particularly promising as a second-line nonnicotine pharmacotherapy,
and its efficacy does not appear to depend on the presence of co-occurring
depressive symptoms or major depressive disorder (795, 814). However,
the side effects of nortriptyline are more prominent than those
of NRTs or bupropion, and nortriptyline is also toxic in overdose
amounts (455, 815–817). Clonidine may also have some merit
as a second-line agent (818), but its side effects may limit its
use (819). Acupuncture (788) and other agents (e.g., naltrexone,
mecamylamine, buspirone, monoamine oxidase inhibitors [MAOIs],
SSRI antidepressants) (603, 795, 820–823) have also been
studied, but their efficacy for smoking cessation has not been established.
+
F. Psychosocial Treatments
There is extensive evidence of the efficacy of psychosocial
therapies for treating individuals with nicotine dependence, whether
delivered in a group (824) or individual (825) format. These therapies
are typically provided as a multimodal package of several specific treatments
and aim to provide patients with the skills to quit smoking and
avoid smoking in high-risk situations. Behavioral coping skills
may include removing oneself from the situation, substituting other
behaviors (e.g., walking, exercising), or using skills to manage triggers
(e.g., assertiveness, refusal skills, time management). Cognitive
coping skills may include identifying maladaptive thoughts, challenging
them, and substituting more effective thought patterns to prevent
a slip from becoming a relapse (e.g., not viewing the slip as a
catastrophe). The 6-month quit rates for behavioral therapies in
general are typically 20%–25%, or about
twofold greater than quit rates with control conditions (824–828).
A review of behavioral therapy studies also suggests that 1) more
intensive behavioral therapies can produce better treatment outcomes
versus low-intensity interventions (701, 703), and 2) behavioral
therapies can augment smoking cessation outcomes with pharmacotherapies,
including all NRTs and bupropion (414, 701, 703, 704).
Social support appears to be of benefit in encouraging an
individual to quit smoking, whether it is measured according to
the degree of support provided by a spouse or partner (829) or is
provided in the form of a specific intervention (e.g., buddy system)
(718, 826, 828, 830–833). Thus, social support is recommended
as a treatment for smoking cessation.
Brief therapies, such as behavioral supportive cessation counseling,
may lead to enhanced rates of treatment retention or smoking cessation
(639, 826, 828, 834–837). Such therapies can often be implemented
successfully and economically in a broad range of health care settings.
These therapies often incorporate elements of MET and encourage
the patient to examine the reasons for and against quitting smoking.
When brief interventions are used, patients are likely to have a
greater number of quit attempts and a greater likelihood of success
in smoking cessation (825, 826, 828).
+
3. Behavioral therapies
Behavioral therapies are recommended as a first-line treatment
for smoking cessation, with a large database of over 100 controlled
prospective studies on multimodal behavioral therapy supporting
this recommendation (720, 734, 735, 826, 838). In most reviews and meta-analyses,
6-month quit rates with behavioral therapy are double those observed
in control groups (824, 826, 828) and similar to long-term outcomes
obtained with NRTs and bupropion. Specific types of behavioral therapy
that have also been studied include contingency management, cue
exposure, and "rapid smoking" aversion therapy;
however, none of these are sufficiently well studied to support
their use clinically.
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4. Cognitive-behavioral
therapies
Several controlled studies suggest that CBTs are effective
for smoking cessation (700, 839, 840) and are possibly effective
for smokers with comorbid depressive symptoms, major depression,
and alcohol and other substance use disorders (456, 459, 841–844).
CBT may also help in addressing weight concerns associated with
smoking cessation (840). However, the long-term effectiveness of
CBT in this population has not been established.
+
5. Self-guided therapies
Self-help materials are designed to increase patients' motivation
to quit smoking and teach them smoking cessation skills. In most
(845–853) but not all (854, 855) studies, approaches such
as community support groups, telephone counseling, written manuals,
videos, and computer-generated, tailored self-help materials have
shown promise in increasing smoking cessation rates. The use of
multiple modes of therapy (e.g., written materials plus phone contact)
(718, 720, 721, 856–859) and tailoring materials to the
specific needs and concerns of each patient improves the effectiveness
of self-help methods (736, 851, 860).
A number of other psychosocial therapies have been evaluated
in a small number of clinical trials, with the results showing variable
success. For example, some evidence suggests that exercise programs
may help prevent a relapse to smoking in women (861, 862), whereas
other studies do not (863, 864). However, based on the other health
benefits of exercise, increased activity is encouraged in smokers
attempting to quit or those who have recently quit smoking. There
is also some support for the effectiveness of stimulus control techniques
in reducing smoking urges, such as discarding cigarettes; removing
ashtrays, lighters, and matches; avoiding smokers; and avoiding
situations associated with smoking (718). However, these strategies
are probably best used within the context of multicomponent therapies.
Little evidence is available that would support the use of physiological
feedback (i.e., giving immediate positive feedback on the benefits
of smoking cessation such as decreasing carbon monoxide levels),
gradual cessation (i.e., "nicotine fading"), or
relaxation techniques (718). In addition, there is an insufficient
number of studies of adequate research design regarding the use
of 12-step programs, hypnosis, biofeedback, family therapy, IPT,
or psychodynamic therapies for treating nicotine dependence, although
clinical consensus suggests that such therapies may be useful in
some patients.
+
G. Treatment of Smokers
on Smoke-Free Wards
This section focuses on the treatment of psychiatric patients
on smoke-free wards, a common issue confronted by psychiatrists.
The principles described also apply to smokers on general medical
wards seen in consultation and to smokers in smoke-free nonmedical settings,
such as residential care settings. Controlled studies of treating
nicotine withdrawal symptoms on psychiatric inpatient wards have
not been published; thus, the recommendations below are based on
treating withdrawal in outpatient settings (755, 757).
An inpatient stay may be an opportune time for initiating
treatment for nicotine dependence because of the intensity of exposure
to medical staff, diagnosis of medical conditions, and removal from
usual smoking cues. It may therefore be helpful to include smoking cessation
on the master treatment plan whenever relevant. As in other settings,
smokers should be assessed for their readiness and motivation for
change (32). Those considering quitting should be asked about their
interest in using the temporary abstinence of the smoke-free unit
as a beginning step toward permanently stopping smoking. In addition
to the aspects of assessment discussed above in Section III.B, it
may also be helpful to elicit from the patient any history of withdrawal
symptoms in prior hospitalizations, withdrawal during prior voluntary
quit attempts, or significant fear of withdrawal. An important but
often neglected issue is the incorporation of NRTs and smoking cessation-related
advice and aftercare into treatment plans on patient discharge (865).
Although many inpatient units have been concerned about implementing
smoke-free units, most have found it less difficult than anticipated
(34, 866, 867). Most (34, 866, 868–870) but not all (871)
reports before and after the institution of smoke-free units indicate
no increases in aggression, disruption, discharges against medical
advice, use of medications or restraints, or admission refusals.
However, a recent retrospective study on a smoke-free unit suggested
that smokers may be more likely to be irritable or agitated than
nonsmokers and that smokers who are not prescribed an NRT were more
likely to be discharged against medical advice than other patients
(865). Giving special off-ward privileges to allow patients to smoke
or labeling off-ward passes as "smoking breaks" implicitly
condones smoking (34, 866). In addition, there are risks in allowing
some patients to have smoking breaks, such as patients with suicidal
ideation or those with a history of eloping or exhibiting other problematic
behavior on passes. Policies that provide breaks for smokers and
nonsmokers on the same schedule may be preferable to policies that
provide smokers with extra passes. Other recommendations for implementing
a smoke-free unit are discussed in reviews (34, 866).
Patients need to be educated about the rationale for a smoke-free
unit; that is, that its purpose is not to force patients to stop
smoking but to prevent secondhand smoke exposure to other patients
and be consistent with the institution's goal to encourage
healthy behaviors (34, 866). Patients should also be educated about
the goal of smoking cessation treatment: to reduce withdrawal symptoms
and, if patients are interested, to help them begin a cessation
attempt (see Section III.D.9). Many patients are unaware of the
valid symptoms of nicotine withdrawal and their time course; thus
education about these can be helpful (34, 866).
+
3. Monitoring of
symptoms
Although true for all individuals who stop smoking, it is
particularly important to monitor patients in smoke-free inpatient
settings for changes in psychiatric symptoms. Smoking cessation
can worsen anxiety, insomnia, concentration, and weight gain, thereby
confounding assessment and treatment of the patient's other
psychiatric disorders (865). For example, because many alcohol-dependent
patients smoke, it may not be clear whether their irritability,
anxiety, insomnia, restlessness, difficulty concentrating, and depression
are due to alcohol or nicotine withdrawal during alcohol detoxification
on a smoke-free ward. Although nicotine withdrawal symptoms are
thought to be milder than alcohol withdrawal symptoms, there is
substantial person-to-person variability so that some alcohol-dependent smokers
have nicotine withdrawal symptoms that are more severe than their
alcohol withdrawal symptoms (872). When patients with schizophrenia
are hospitalized and given higher doses of medications to treat
acute psychosis, any increases in restlessness could be due to nicotine
withdrawal rather than to neuroleptic-induced akathisia. Further
confounding the source of the increased symptoms is the fact that
smoking cessation can cause dramatic increases in blood levels of
some medications (e.g., those metabolized by the CYP 1A2 microsomal
system) (760, 873). In particular, clozapine levels can increase
by up to 40% with smoking cessation (874).
+
4. Treatment of withdrawal
symptoms
For some individuals, nicotine
withdrawal during hospitalization is often not as severe as anticipated
because of the absence of smoking cues, the distraction of the primary
psychiatric problem, and the effects of medications. However, a
recent retrospective study suggests there are clear benefits of
providing NRTs to smokers on smoke-free inpatient psychiatric units
(865), findings that are consistent with recommendations of the
U.S. Agency for Healthcare Research and Quality's A
Clinical Practice Guideline for Treating Tobacco Use and Dependence (826)
and with a meta-analysis of studies in nonpsychiatric inpatients
(875). Thus, given the low risk of NRTs, prophylactic treatment
with an NRT is suggested for all psychiatric inpatients who smoke.
The advantages of nicotine gum in this context include the patient's ability
to self-titrate the nicotine dose and stop using the gum immediately
before intermittent smoking (e.g., during passes). In addition,
many patients find that only a few pieces of gum per day are sufficient
to prevent withdrawal symptoms (34, 866). The nicotine patch has
the advantage of improved adherence and providing stable nicotine
replacement. This may be especially advantageous in patients for
whom a clinician is trying to differentiate nicotine withdrawal
symptoms from psychiatric symptoms (873). For highly nicotine-dependent
individuals, the use of more than one form of NRT (e.g., nicotine
patch plus gum) may be helpful (865). A frequent question about
prescribing NRT to patients on smoke-free units relates to those
individuals who do not wish to stop smoking entirely and may use NRTs
and cigarettes concurrently. However, such use of NRTs appears to
be unlikely to produce significant adverse effects (865, 876–881).
Bupropion can also be used in inpatient settings given its fixed
dosing, easy monitoring, and efficacy in reducing signs and symptoms
of the withdrawal syndrome (158).
Although the existing evidence does not show direct effects
of psychosocial treatments on withdrawal symptoms, clinical experience
suggests several strategies that may be useful for individuals in
inpatient settings. Relaxation tapes can be used to alleviate anxiety.
Anger can be averted by temporarily avoiding interactions; insomnia
can be decreased by improving sleep hygiene; weight gain can be
combated by increasing activity; and distraction and activities
aimed at keeping busy can be used to get through craving episodes.
Support groups for those going smoke free and support from family
and significant others for going smoke free can be helpful as well.
+
H. Clinical Features
Influencing Treatment
+
1. Use of multiple
substances
There is strong evidence that rates of smoking are much higher
in patients with a substance use disorder than in the general population
(347). For example, in the National Epidemiologic Survey on Alcohol
and Related Conditions, the 12-month prevalence of nicotine dependence
is 34.5% among individuals with any alcohol use disorder
and 52.4% among individuals with any drug use disorder
(347). Conversely, among subjects with nicotine dependence, the
12-month prevalence of an alcohol use disorder is 22.8% and
that of a drug use disorder is 8.2%, rates that are 4.4-
and 8.1-fold higher, respectively, those observed in non-nicotine-dependent
individuals (347). A similar association between nicotine dependence
and other substance use disorders has been observed in data from
the National Comorbidity Study (349). In addition, the presence
of alcohol or illicit drug use may be a negative predictor of smoking
cessation treatment outcomes (698, 872). Although substance use
and smoking are often concurrent and conditioned effects may be
one important factor in determining the high rates of comorbidity
and treatment failure, rates of smoking cessation among these individuals
can still be substantial (349). In addition, many individuals with
a substance use disorder express an interest in smoking cessation.
In patients who do not express a current interest in quitting, motivational
interventions should be used.
There is conflicting evidence about whether concurrent smoking
cessation can increase, decrease, or affect at all the risk of relapse
to alcohol (38), and it is also unclear whether cessation should
be attempted concurrently or after initial abstinence from other
substances. For these reasons, this decision may be guided by patient
preference. In addition, there are few studies of pharmacotherapies
in individuals with substance use disorders (705), but there is
some evidence for the utility of NRT and behavioral approaches.
The use of alcohol treatment-related pharmacotherapies such as disulfiram
or naltrexone might be considered in alcohol-dependent smokers,
but there are no empirical studies to suggest the efficacy of these
therapies in smoking cessation. In any case, such smoking cessation
treatment should be made available in substance use disorder treatment
programs.
+
2. Treatment in the
presence of specific co-occurring psychiatric disorders
In the presence of a co-occurring psychiatric disorder, smoking
cessation may be more difficult (349, 698, 760, 882). Psychiatric
patients appear to have more withdrawal symptomatology when they
stop smoking (414, 703, 767), probably as a function of their higher levels
of nicotine dependence and smoking consumption. Cessation rates
with NRTs (702, 703, 883) appear promising in patients with serious
psychiatric disorders. Nicotine nasal spray and vapor inhaler systems
provide faster delivery of nicotine, which may increase the rewarding
effects of their use. However, no specific studies on these systems
have been published in psychiatric patients, and the degree of difficulty
of using these delivery systems and their side effects may limit
their utility in this population (758, 884). Although many psychiatric
patients smoke large numbers of cigarettes and inhale cigarette
smoke deeply (885), using higher-than-normal doses of nicotine for
heavier smokers has not been consistently shown to be more effective
(790, 886). However, supplementation of the nicotine patch with
ad libitum use of nicotine gum, lozenges, or inhaler appears helpful
(887, 888). NRTs may also be considered as a way to reduce smoking
even when patients do not have smoking cessation as a goal.
Initial psychosocial interventions for psychiatric patients
may need to include higher intensities of behavioral therapy, because
briefer psychosocial treatments are often unsuccessful (414, 702–704).
There has been little study of behavioral therapies for smoking cessation
in chronic psychiatric patients, although preliminary studies provide
modest evidence that higher-intensity therapies may improve outcomes
(701, 703). These studies have typically lacked a treatment as usual
or minimal intervention controls, necessitating more controlled
studies to establish the efficacy of these treatments. Combining
higher-intensity behavioral treatments with an NRT or bupropion
should be considered and has shown some modest success rates in
preliminary studies (414, 701, 703, 704). In addition, psychiatric patients,
including those who abuse or are dependent on substances, are more
likely to benefit from behavioral therapy because of their high
incidence of psychosocial problems, poor coping skills, and often,
history of benefit from such therapy (730). When deciding between individual
or group therapy, it is important to consider patient preference,
as many psychiatric patients have experience with one or both kinds
of psychotherapy. For some patients, both individual and group therapy
may be indicated; for example, a specific problem that undermines
cessation (e.g., a problem with assertiveness) might be addressed
by individual therapy, whereas smoking cessation in general might
be addressed in group therapy. Patients with low levels of coping
skills or supports might also benefit from both individual and group
behavioral therapy.
Rates of smoking in patients with schizophrenia are much higher
(58%–88%) than in the general population
(349, 889). The motivation to address smoking is often poor in these
patients (882, 890), and thus motivational interventions as initial
treatments are strongly suggested (891). In addition, the very low
quit rates observed for these patients (349) suggest that more intense
interventions are needed. Several controlled trials (414, 701–704)
using combinations of higher-intensity behavioral support and pharmacotherapies
(NRTs or bupropion) have shown modest short-term cessation rates,
whereas one open-label trial of bupropion and supportive group therapy
showed a decreased consumption of cigarettes in patients with schizophrenia
(415). Concurrent alcohol and drug abuse in individuals with schizophrenia
is high and can complicate cessation efforts; most studies have
attempted cessation in patients whose drug use is in recovery and
whose psychiatric symptoms are stable. Regular monitoring of antipsychotic
side effects and plasma concentrations may be needed because smoking
cessation may increase levels of antipsychotic medications that are
metabolized via the CYP 1A2 system (e.g., clozapine, olanzapine,
fluphenazine, haloperidol) (see Section III.D.8.b.2). There is some
evidence that in smokers with schizophrenia, the use of second-generation
antipsychotic agents can either reduce smoking (e.g., clozapine)
in those not wanting to quit (407) or facilitate cessation in those
attempting to quit with the nicotine patch (703) or bupropion (414),
but further studies of this effect are needed in larger samples.
+
b) Depressive disorders
Individuals with major depressive or dysthymic disorder also
have high rates of smoking, with 12-month prevalence rates of about
30% (347). Similarly, about 17% of nicotine-dependent
individuals have a 12-month prevalence of major depressive disorder
(347), and 40% of smokers seeking treatment have a history
of depression (760, 781). Current (765, 892, 893) and perhaps past
(894) depression appears to be a negative predictor of treatment outcome
during smoking cessation. Although pharmacotherapies for smoking
cessation have not been carefully tested in patients with current
(458) or past (456) major depression, antidepressants such as bupropion
(158) or nortriptyline (456) should be strongly considered. In general,
SSRIs do not appear to be efficacious in promoting smoking cessation (602, 795). Behavioral therapies such as CBT should also be considered
for depressed smokers (456, 459, 893, 895), as these individuals
are likely to fail with more minimal interventions. After a patient
has quit smoking, his or her plasma levels of some antidepressants
(e.g., TCAs) that are metabolized by CYP 1A2 may increase, necessitating
close monitoring of levels and antidepressant side effects.
+
c) Other psychiatric
disorders
Smoking rates in patients with a bipolar or anxiety disorder
(e.g., PTSD, panic disorder), ADHD, or another substance use disorder
(e.g., marijuana, opioids, cocaine) are also higher than in the
general population, but there has been little study of factors associated
with these patients' interest in quitting smoking or the
efficacy of smoking cessation interventions with these patients
(698, 699).
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3. Comorbid general
medical disorders
Nicotine dependence is the most frequent substance use disorder
in all medical settings. In 2001, an estimated 46.2 million adults
in the United States smoked cigarettes (896). A 2004 report of the
U.S. Surgeon General (897) concluded that there is sufficient evidence to
infer a causal relation between smoking and many medical conditions,
including cancer and cardiovascular and respiratory diseases. Despite
improved public awareness of its dangers, tobacco use continues
to be the leading preventable cause of disease and death in the United
States, leading to approximately 440,000 deaths per year (898).
Because the duration of smoking is a substantial contributor to
the associated harms from inhalation of tar and carbon monoxide,
early intervention is important if smoking-related morbidity and mortality
are to be prevented.
It is not surprising that smokers with psychiatric disorders
have an increased risk for nicotine-related medical disorders because
individuals with a psychiatric and/or a substance use disorder
are two to three times more likely to be dependent on nicotine than
the general population (347) and smokers with psychiatric disorders
consume nearly half of all the cigarettes consumed in the United
States (349). In addition, many of these individuals are obese,
consume harmful levels of alcohol and salt, and do not exercise
or undergo cholesterol screenings (899). As well as having increased
medical comorbidity, smokers on psychiatric or other medications
that are metabolized through CYP 1A2 will require higher medication
doses compared with nonsmokers (414, 698, 760, 768, 769).
Environmental tobacco smoke (secondhand smoke) also contributes
to increased morbidity and mortality and has been classified by
the U.S. Environmental Protection Agency as a known cause of lung
cancer in humans (group A carcinogen). Secondhand smoke is estimated
by the agency to cause approximately 3,000 lung cancer deaths in
nonsmokers each year (900). Given the high proportion of individuals
with psychiatric disorders who smoke, those who reside or attend
treatment programs with large numbers of other smokers may be at
increased risk from environmental tobacco smoke.
+
b) Issues related
to specific physical disorders
Cardiovascular disease, lung cancer, and chronic obstructive
pulmonary disease are the most common causes of morbidity and mortality
among smokers, making it important to screen smokers for the signs
and symptoms of these conditions (751, 901). Among smokeless tobacco,
cigar, and pipe users, mouth and upper airway cancers are the most
common causes of tobacco-induced mortality, and users of these forms
of tobacco should be screened for the presence of these diseases
(751, 901).
With smoking-related physical disorders, the duration of smoking
abstinence is directly related to decreases in risk within 5 years
of cessation (902–906). Smoking cessation also leads to
an improved quality of life. Because medical hospitalization, cancer
diagnosis, impending surgery, or exacerbation of cardiorespiratory
symptoms may motivate individuals to consider smoking cessation,
treatment for nicotine dependence is particularly important at these
junctures. Screening for other substance use is also indicated,
as smokers with pulmonary problems may be highly dependent and have
a comorbid alcohol use disorder.
In general, the treatments for nicotine dependence that are
recommended for use in the general population are effective in patients
with co-occurring general medical conditions. NRTs decrease acute
symptoms of nicotine withdrawal and increase smoking cessation rates
(839, 907–912) without appearing to have any increased
risk of adverse outcomes (836, 876, 913–916). Bupropion
also appears to be safe as well as effective in individuals with
cardiovascular (917) and pulmonary disease (918). Behavioral interventions
improve smoking cessation rates when administered alone (875, 919, 920), as a package of several behavioral interventions (836, 875, 920, 921), or in combination with an NRT (908, 911, 912); they appear
particularly useful when delivered in more intensive formats (855, 875, 920) or in conjunction with a program of smoking cessation
aftercare (836, 875, 920, 921).
Pregnant women who smoke pose an immediate and considerable
challenge, given the risks of smoking to the fetus (574, 922–928).
Screening patients for their smoking status during pregnancy is
essential, and biochemical measures may be more accurate than self-report
measures in identifying those in need of intervention (929). The
primary risk of smoking during pregnancy appears to be low-birth-weight
infants. If a woman quits smoking by her third trimester, the risk
of giving birth to a low-birth-weight infant is no greater than
the risk to a nonsmoker (930–935).
There is good evidence that physician counseling about smoking
during pregnancy is effective (936, 937). In addition, behavioral
interventions may be preferred by many women (938, 939); thus, these
interventions should be considered first-line treatments for pregnant smokers
(939).
The evidence is mixed on the ability of NRTs to augment rates
of smoking cessation in pregnant women compared with behavioral
interventions alone (940, 941). Although there appears to be no
increased risk for NRTs in pregnancy (930, 938), this has not been
well studied. Nevertheless, the consensus suggests that any increase
in risk that might occur with NRTs is likely to be less than the
risk of ongoing smoking (942, 943). Intermittent forms of NRTs may
be preferred over the nicotine patch as the former minimize nicotine
exposure to the fetus (930). Although there are no reports on the
teratogenicity of bupropion, the decision to treat a pregnant woman
with bupropion should include consideration of the potential benefits
and risks to the woman and the fetus.
Regardless of the form of treatment used to augment smoking
cessation in pregnant women, postpartum relapse rates are high (738, 929, 944, 945), suggesting a need for additional efforts at relapse
prevention.
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IV. Treatment of
Alcohol-Related Disorders
The focus of this section is on the treatment of patients
with alcohol dependence or abuse. However, treatment of these disorders
may be complicated by episodes of intoxication and withdrawal, the
treatment of which is discussed in Sections IV.C.1 and IV.C.2. Alcohol
use disorders are common. In the National Epidemiologic Survey on
Alcohol and Related Conditions, the 12-month prevalences were 4.65% for
alcohol abuse and 3.61% for alcohol dependence (23), with
corresponding 12-month prevalences in the National Comorbidity Study
of 3.1% and 1.3%, respectively (946), and prevalences
of lifetime disorder that were about five times the 12-month prevalences
(947).
The course of alcohol use disorders is variable and frequently
characterized by periods of remission and relapse. The first episode
of alcohol intoxication is likely to occur in the mid-teens, and
the age at onset of alcohol dependence peaks at ages 18–25
years (947, 948). The first evidence of withdrawal, if it occurs,
is not likely to appear until many other aspects of dependence have
developed. Although some individuals with alcohol dependence achieve
long-term sobriety without active treatment, others need treatment
to stop the cycles of remission and relapse (949).
The relation of alcohol dependence to alcohol abuse is also
variable. In one study (950), only 30% of male subjects
with alcohol abuse at baseline met criteria for alcohol dependence
4 years later; the other 70% either continued to meet criteria
for alcohol abuse or saw their alcohol problems remit entirely.
The long-term goals of treatment for patients with an alcohol
use disorder are identical to those for patients with any type of
substance use disorder and include abstinence (or reduction in use
and effects), relapse prevention, and rehabilitation. There is some
controversy in the literature, however, regarding the possible benefits
of striving for a reduction in alcohol intake, as opposed to total
abstinence, for those who are unlikely to achieve the latter. A
comprehensive review of the issue (951) concluded that a lower severity
of pretreatment alcohol dependence and an individual's
belief that he or she could control his or her drinking were associated
with the individual's achieving controlled drinking after
treatment. Interventions aimed at achieving moderate drinking have
also been used with patients in the early stages of alcohol abuse
(952, 953). Controlled drinking may be an acceptable outcome of
treatment for a select group of patients when it is accompanied
by substantial improvements in morbidity and psychosocial functioning.
However, abstinence is the optimal goal that achieves the best long-term
overall functioning (9).
Numerous studies (43, 954, 955) have documented positive outcomes
among individuals who receive treatment for alcohol dependence;
approximately 70% of all such patients manifest a reduction
in the number of drinking days and improved health status within
6 months (43).
The majority of patients who are treated for an alcohol use
disorder have at least one relapse episode during the first year
after treatment. However, there is considerable evidence to show
that most individuals with an alcohol use disorder drink less frequently
and consume less alcohol after receiving treatment compared with
before treatment (956–959). For example, patients typically
report drinking heavily on 75% of the days during a 3-month period
before treatment, whereas during posttreatment follow-ups, they
report being abstinent on 70%–90% of
the days and engage in heavy drinking on 5%–10% of
the days (231).
Treatment has also been shown to bring about improvements
in family functioning, marital satisfaction, and psychiatric impairments
(43, 290, 960–963). Although improvements after treatment
for alcohol dependence are at least in part attributable to nontreatment
factors such as patient motivation (964), it is generally accepted
that treatment does make a difference, at least in the short run.
The choice of treatment setting for an alcohol-dependent individual
will be determined by the results of the initial medical and psychiatric
evaluation (see also Section II.C). In addition, the optimal treatment
setting and subsequent treatment outcome are likely to vary depending
on the characteristics of the individual patient (965, 966).
Patients with alcohol withdrawal must be detoxified in a setting
that provides for frequent clinical assessment and the provision
of any necessary treatments (967). Some outpatient settings can
accommodate these requirements and may be appropriate for patients deemed
to be at low risk for a complicated withdrawal syndrome, with medical
detoxification being accomplished using the medications described
below (see Section IV.C.3). Postdetoxification treatment can also
be successfully conducted outside of the hospital (e.g., in outpatient,
day hospital, or partial hospitalization settings) for most patients
with alcohol dependence or abuse (51, 956, 967). Intensive outpatient
care involving frequent visits or conducted in a day hospital is
generally preferable for the early phase of treatment. It is usually
preferred that a significant other be available for travel to and
from the treatment site, medication monitoring, symptom evaluation,
support for abstinence, and communication with a responsible health
care professional on behalf of the alcoholic patient. Relapse prevention
medications should always be considered after detoxification. Currently
available medications are naltrexone, disulfiram, and acamprosate
(see Sections IV.C.3.a–c).
Patients who are unlikely to benefit from less intensive and
less restrictive alternatives may need to be hospitalized at times
during their treatment. In particular, those who have a history
of withdrawal seizures or delirium tremens, whose documented history
of very heavy alcohol use and high tolerance places them at risk
for a complicated withdrawal syndrome, who are concurrently abusing
other substances, who have a severe comorbid general medical or
psychiatric disorder, or who repeatedly fail to cooperate with or
benefit from outpatient detoxification are more likely to require
a residential or hospital setting that can safely provide the necessary
care. Patients in severe withdrawal (i.e., delirium tremens) always
require treatment in a hospital setting. Patients who fail to achieve
abstinence or who relapse frequently should also be given a trial
of inpatient care. Under some circumstances, psychiatrically or
socially unstable individuals may similarly benefit from the stabilization
provided by a residential treatment setting.
Inpatient care should include medical detoxification and a
program of rehabilitation. Although many inpatient and residential
treatment programs have been traditionally organized around a treatment
length of 28 days, empirical studies have not yet identified a specific
optimal length of stay for the treatment of patients with an alcohol
use disorder. Moreover, 28 days is a brief period in the natural
history of a chronic disease.
Regardless of whether treatment for an alcohol use disorder
begins in an inpatient or outpatient setting, the pivotal factor
in successful treatment is engaging the patient in long-term outpatient
relapse prevention with a duration measured in years rather than
days. Patients should also be encouraged to participate in 12-step
or other self-help group programs during outpatient rehabilitation.
+
1. Treating intoxication
states
In general, the acutely intoxicated patient requires reassurance
and maintenance in a safe and monitored environment in which efforts
are made to decrease external stimulation and provide orientation
and reality testing. Adequate hydration and nutrition are also essential. Clinical
assessment should follow the general guidelines described in Section
II.B, giving particular emphasis to the patient's general
medical and mental status, substance use history, and any associated
social problems. Patients presenting with signs of intoxication
should also be assessed for the possibility of recent use of other
substances that could complicate their clinical course. Patients
with a history of prolonged or heavy drinking or a history of withdrawal
symptoms are at particular risk for medically complicated withdrawal
syndromes and may require hospitalization.
+
2. Treating withdrawal
syndromes
The treatment of alcohol withdrawal has two major goals: 1)
help the patient achieve detoxification in a manner that is as safe
and comfortable as possible and 2) enhance the patient's
motivation for abstinence and recovery (968). According to DSM-IV-TR,
the syndrome of mild to moderate alcohol withdrawal generally occurs
within the first several hours after the cessation or reduction
of heavy, prolonged ingestion of alcohol. It includes signs and
symptoms such as gastrointestinal distress, anxiety, irritability,
elevated blood pressure, tachycardia, and autonomic hyperactivity.
The syndrome of severe alcohol withdrawal, including delirium
tremens, occurs especially within the first several days after cessation
or reduction of heavy, prolonged ingestion of alcohol; the syndrome
includes signs and symptoms such as clouding of consciousness, difficulty
in sustaining attention, disorientation, generalized tonic-clonic
seizures (grand mal) seizures, respiratory alkalosis, and fever
(969–971). As described in DSM-IV-TR and elsewhere (972, 973), <5% of individuals with alcohol withdrawal develop
severe symptoms and <3% develop grand mal seizures.
In the past, the mortality rate for patients experiencing alcohol
withdrawal delirium was as high as 20%; currently, it is
closer to 1% because of improved diagnosis and medical
treatment (972). The presence of a co-occurring medical disorder
may also increase the likelihood of a complicated withdrawal syndrome
(974–976). Because mounting evidence suggests that repeated
episodes of alcohol withdrawal may lead to a worsening of future
withdrawal episodes (a phenomenon known as the alcohol withdrawal
kindling or sensitization effect), individuals with multiple previous
withdrawals may require more aggressive treatment (977). To aid
in identifying individuals at risk for severe alcohol withdrawal,
a number of standardized instruments have been developed that assess
and qualify the severity of withdrawal symptoms, with perhaps the
most widely used being the Clinical Institute Withdrawal Assessment
for Alcohol Scale, Revised (978, 979).
For approximately 67% of the patients with mild to
moderate withdrawal symptoms, generalized support, reassurance,
and frequent monitoring are sufficient treatment (980), although
the effectiveness of supportive treatment for these patients relative
to pharmacotherapy is not well established (981, 982). In one case-control
study (981), 74% of hospitalized alcohol-dependent patients
without a serious comorbid general medical problem responded to
supportive treatment for alcohol withdrawal. Consensus does suggest
that thiamine be given routinely to all patients receiving treatment
for a moderate to severe alcohol use disorder to treat or prevent
common neurological sequelae of chronic alcohol use (983–986).
In addition, patients in more severe withdrawal and those who develop
hallucinations require pharmacological treatment.
The criteria for an ideal pharmacological agent to treat alcohol
withdrawal include effectiveness in relieving symptoms and preventing
seizures and delirium; a benign side effect profile, including safety
in overdose; limited interactions with other medications; tolerability
by those with comorbid medical conditions; tolerability by outpatients
who may have cognitive impairment; and the ability to suppress drinking
during and after alcohol withdrawal (987). Because no single agent
or class of agents meets all of these criteria, a pharmacotherapeutic
agent needs to be chosen according to the needs of the individual
patient.
There are numerous reviews of the pharmacological treatment
of moderate to severe withdrawal (987–993). The pharmacotherapy
is directed toward reducing CNS irritability and restoring physiological
homeostasis. This often requires the use of fluids, benzodiazepines,
and, in selected cases, other medications (138, 987, 992, 994),
as described below. In particular, benzodiazepines effectively reduce
withdrawal severity and the incidence of seizures and delirium (991, 992). Carbamazepine, beta-blockers, and clonidine also diminish
the severity of alcohol withdrawal symptoms but have not been proven
to prevent delirium or seizures, which suggests that beta-blockers,
clonidine, carbamazepine, and neuroleptics can be used adjunctively
but not as monotherapy (992). In fact, there is some suggestion
that protracted withdrawal symptoms and the relapse rate that occurs
after successful detoxification may depend in part on what type
of agent (benzodiazepine or anticonvulsant) is used during the acute
detoxification period (977).
Additional factors need to be taken into consideration when
choosing a medication in an outpatient detoxification setting. It
is clear that benzodiazepines can cause sedation and, if used with
alcohol, can be especially dangerous. Use of an anticonvulsant agent
such as carbamazepine may be considered. Anticonvulsants, clonidine,
and beta-blockers do not have the abuse potential of benzodiazepines
and are not likely to be diverted for other uses. These factors
may be particularly important in the outpatient detoxification of
a person who abuses multiple substances.
The use of benzodiazepines to control withdrawal symptoms
takes advantage of the cross-tolerance between alcohol and this
class of medication (972). A substantial body of evidence, including
several meta-analyses (991, 992, 995), supports the use of benzodiazepines
in the treatment of alcohol withdrawal.
The literature is less clear about specific benzodiazepines
or a specific protocol for detoxification with benzodiazepines.
Some authors suggest a single oral loading dose of 200–400
mg chlordiazepoxide or 20–40 mg diazepam, or as needed,
may be used (996, 997). Orally administered chlordiazepoxide (50
mg every 2–4 hours), diazepam (10 mg every 2–4
hours), oxazepam (60 mg q2h), and lorazepam (1 mg q2h) are commonly
used (982, 998). Another approach is to take the total dose necessary
to suppress CNS irritability and autonomic hyperactivity in the
first 24 hours (i.e., the stabilization dose) and give it in four
divided doses the following day, after which the dose can usually
be tapered over 3–5 days, with monitoring for reemergence
of symptoms (999). For most patients, the equivalent of 600 mg/day
of chlordiazepoxide is the maximum dosage, and many patients require less;
a few, however, may require substantially more (1000). Patients
in severe withdrawal and those with a history of withdrawal-related
symptoms may require up to 10 days of treatment before benzodiazepines
can be completely withdrawn. Benzodiazepine administration should
be discontinued once detoxification is completed. Multiple randomized, controlled
trials demonstrate the use of less medication as well as shorter
duration of treatment in symptom-triggered detoxification protocols
(998, 1001–1003).
For patients who have severe hepatic disease, are elderly,
or have delirium, dementia, or another cognitive disorder, short-acting
benzodiazepines such as oxazepam or lorazepam (1004) are preferred
by some clinicians and appear to be efficacious (1005). Oxazepam
and lorazepam do not require multistep biotransformation; they are
metabolized by phase II enzymes (glucuronidation) that are not as
affected by alcohol-related hepatitis. Glucuronidation is preserved
even in severe liver disease and cirrhosis (1006, 1007), making
these medications safer choices for such patients. Lorazepam also
has the advantage of being able to be administered parenterally.
However, because of their brief half-lives, the short-acting benzodiazepines
need to be given more frequently (1008–1011).
+
b) Adrenergic agonists
and antagonists
Beta-adrenergic antagonists (e.g., propranolol, 10 mg p.o.
q6h) have been used to reduce signs of autonomic nervous system
hyperactivity (e.g., tremor, tachycardia, elevated blood pressure,
diaphoresis) and, at higher doses, arrhythmias (1012–1014).
Atenolol has been used for a similar purpose, usually in combination
with benzodiazepines (1015), thus allowing the use of lower doses
of benzodiazepines and thereby reducing the sedation and cognitive
impairment often associated with benzodiazepine use. Clonidine,
an -adrenergic agonist
(0.5 mg p.o. b.i.d. or t.i.d.) has been shown to reduce tremor,
heart rate, and blood pressure (1016, 1017). However, the use of
beta-blockers or clonidine alone for the treatment of alcohol withdrawal
is not recommended because of their lack of efficacy in preventing
seizures (992).
The use of anticonvulsants as a treatment for acute alcohol
withdrawal has been investigated in several studies (977, 994, 1018–1020)
and considered in two meta-analyses (991, 992) and a review (987).
Anticonvulsants and benzodiazepines appear to have comparable efficacy
in preventing seizures during alcohol withdrawal (995); however,
the prophylactic use of anticonvulsants such as phenytoin is not
generally recommended (1005, 1021–1023) except in individuals
with a co-occurring seizure disorder who have stopped their anticonvulsant
medications while drinking (1024). Other withdrawal symptoms may
also be diminished by anticonvulsants (992, 994, 1018, 1020), particularly
in patients with mild to moderate withdrawal, although the evidence
for this is mixed (987) and sample sizes of studies considering
this usage have generally been small, making meta-analysis problematic
(1025). Carbamazepine (600–800 mg/day for the
first 48 hours; then tapered by 200 mg/day) has also been
demonstrated to be effective in preventing withdrawal-related seizures,
although its tendency to lower white blood cell counts in some patients
may pose an added risk of infection (1026–1030). Although
the evidence for the use of oxcarbazepine is sparse, this medication
may be useful as an alternative to carbamazepine (1031). Divalproex
sodium at a dosage of 500 mg t.i.d. (994) and intramuscular magnesium
sulfate (1032) have also been used for preventing withdrawal seizures.
Barbiturates (e.g., pentobarbital, phenobarbital, secobarbital)
may be useful in reducing withdrawal symptoms in patients whose
symptoms are refractory to benzodiazepines (1033). However, more
recent reviews indicate that well-controlled studies of phenobarbital
are rare and do not recommend phenobarbital for routine treatment
of alcohol withdrawal (987).
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d) Antipsychotic
agents
For patients manifesting delirium, delusions, or hallucinations,
antipsychotic agents, particularly haloperidol (0.5–2.0
mg i.m. q2h, as needed) are recommended. Because antipsychotic agents
are not effective for treating the underlying withdrawal state (992),
they should be used as an adjunct to benzodiazepines. Most patients
will require <10 mg of haloperidol every 24 hours, although some
patients may require considerably more.
Although some hospitals maintain oral and intravenous ethanol
in their formularies to treat alcohol withdrawal syndromes, there
is no clear evidence for the effectiveness of ethanol in this application.
Given the published evidence of intravenous or oral benzodiazepine
treatment for minor and major abstinence syndromes and the lack
of any controlled trials comparing the use of intravenous benzodiazepines
such as chlordiazepoxide with intravenous ethanol, the use of intravenous
ethanol is not supported by the current published data (1034, 1035).
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3. Medications to
treat alcohol abuse and dependence
Naltrexone, an opiate receptor antagonist, is thought to act
by preventing the opiate receptor-mediated euphoric and rewarding
effects of alcohol, diminishing the rewarding aspects of alcohol-induced
dopamine release, and blunting the subsequent craving for alcohol.
Naltrexone is one of the most widely studied medications for the
treatment of alcohol dependence. Meta-analyses have found it to
be more effective than placebo in promoting abstinence, reducing
heavy drinking days, and decreasing rates of relapse (152–154, 1036). Depending on the study and outcome measure used, naltrexone
is associated with small to moderate benefits (e.g., with effect
sizes of 0.1–0.5 and/or relative risk decreases
of 10%–14%). In addition, individual
responsiveness to naltrexone varies, with some evidence that a family
history of alcoholism and high levels of craving may predict better
naltrexone response.
Some single-site and small multisite trials from several countries
have shown therapeutic benefits of oral naltrexone (187, 954, 1037–1041),
whereas other larger multisite studies have not (1042, 1043). Long-acting
injectable naltrexone also appears to be efficacious (1044). In
a number of these studies, the type and amount of concomitant psychosocial
interventions may confound the interpretation of the study findings
(1042, 1043). Several studies have indicated that naltrexone works
best when combined with a relapse prevention approach, such as coping
skills or CBT (187, 1038, 1039, 1041). Conversely, when more severely
dependent subjects have been studied without concomitant relapse
prevention interventions, the efficacy of naltrexone has been less
robust (1045) or nonexistent (1043).
With the initiation of naltrexone
therapy, patients taking opioids may experience withdrawal symptoms;
therefore, before starting naltrexone, patients should be opioid
free for at least 5 days after the last dose of a short-acting opioid
such as heroin or 7 days after the last dose of a longer-acting
opioid such as methadone (see Section VII.C.1.c). A urine toxicology
screen for opiate medication may be indicated before naltrexone
therapy is initiated. In non-opioid-abusing patients, the 50-mg
dose of naltrexone used in most studies has been associated with
mild and transient side effects, including CNS-related symptoms (headache,
fatigue, dysphoria) and gastrointestinal problems (nausea, vomiting,
abdominal pain). Similar side effects are reported with the long-acting
injectable naltrexone and are more prominent in doses of 380 vs.
190 mg i.m. per month (1044). In addition, injection site pain was
noted in about 10% of patients (1044).
Although significant
hepatoxicity has been reported with naltrexone, this side effect
is rare at the usual doses. Moreover, liver function may improve
in naltrexone-treated patients as a result of decreased drinking
(1046). Hepatotoxicity may be more likely in morbidly obese individuals
or at doses higher than those normally used in clinical treatment
(>100 mg/day). Hepatoxicity resulting from an interaction
between nonsteroidal anti-inflammatory drugs (NSAIDs) and high-dose
naltrexone has also been described (1047); clinicians should use
high doses of naltrexone cautiously and warn patients accordingly.
In addition, because naltrexone is an opioid antagonist, it would
be inappropriate for patients requiring opioid analgesics. The naltrexone-treated
patient should carry a card explaining these issues and provide
it to health care personnel in an emergency.
Treatment with the aversive agent disulfiram (usually 250
mg/day, range 125–500 mg/day) is aimed
at motivating abstinent alcoholic individuals to resist alcohol
consumption. When aldehyde dehydrogenase is inhibited by disulfiram
(151), alcohol consumption causes toxic levels of acetaldehyde to
accumulate, which in turn is associated with a host of unpleasant
and potentially dangerous signs and symptoms, including a sensation
of heat in the face and neck, headache, flushing, nausea, vomiting,
hypotension, and anxiety (148–150). Chest pain, seizures,
liver dysfunction, respiratory depression, cardiac arrhythmias, myocardial
infarction, and death have also been reported. The purpose of disulfiram
is not to make the patient ill but to prevent a patient from drinking
impulsively because he or she knows that illness will result from
drinking while he or she is taking disulfiram. However, disulfiram
is only effective to the degree that an alcohol-using individual
adheres to taking it as prescribed. Methods to improve adherence
include behavioral contracting between an alcohol-dependent individual
and his or her spouse and other forms of monitored administration
with set contingencies.
Controlled trials have not demonstrated any advantage of disulfiram
over placebo in achieving total abstinence, delaying relapse, or
improving employment status or social stability (1048, 1049), and
a meta-analysis showed only some diminution in drinking with disulfiram
(1036). However, a large VA multisite cooperative study did find
that patients receiving 250 mg of disulfiram reported significantly
fewer drinking days than those who either received no disulfiram
or 1 mg of disulfiram (150). Moreover, some clinicians believe that
this medication, when combined with other therapeutic interventions,
has some benefit for selected individuals who remain employed and
socially stable (150, 1048, 1050–1052). Patients who are
intelligent, motivated, and not impulsive and whose drinking is
often triggered by unanticipated internal or external cues that
increase alcohol craving are the best candidates for disulfiram
treatment. Treatment effectiveness is enhanced when adherence is
encouraged through frequent behavioral monitoring (e.g., breath
tests), group support for remaining abstinent (e.g., group therapy,
AA) (1053), contingency contracting, or, where feasible, supervised
administration of disulfiram (1054, 1055).
Disulfiram should never be used without the patient's
knowledge and consent; understanding and explaining disulfiram's
toxic or potentially lethal effects to patients is a prerequisite
for its use (1056–1058). Patients taking disulfiram must
be advised to avoid all forms of ethanol (including, for example,
that found in some cough syrups). Disulfiram requires hepatic metabolism
to convert it into an active medication. A metabolite of disulfiram
is an inhibitor of CYP 450 3A4 (1059) and can interfere with the
metabolism of a variety of psychotropic and other medications that
are substrates for CYP 450 3A4. In addition to its aversive effects
after the ingestion of alcohol, disulfiram can cause a variety of adverse
effects that are rare but potentially severe, including neuropathies
and hepatotoxicity. Thus, it should be used cautiously in patients
with moderate to severe hepatic dysfunction, peripheral neuropathies,
renal failure, and cardiac disease (1048). A patient who is impulsive,
has poor judgment, or has a severe co-occurring psychiatric disorder
(e.g., schizophrenia, bipolar disorder) that makes him or her unreliable
or self-destructive (149, 1060) may also be a poor candidate for
disulfiram treatment. Moreover, disulfiram is eliminated from the
body slowly. Ingesting alcohol even 1–2 weeks after the
last dose of disulfiram could cause an alcohol-disulfiram reaction
(1061).
In 2004 the FDA approved a new medication, acamprosate, for
the treatment of alcohol dependence. The approval was based primarily
on data derived from studies done in Europe (reviewed in 1062, 1063).
Although the neuropharmacological action of acamprosate is not completely
known, researchers do know that it is an amino acid derivative of
taurine that is thought to work at brain glutamate receptor sites
and stabilize glutamatergic function (155). As such, it has been
hypothesized that it might normalize an aberrant glutamate system
present during early abstinence that may be the basis of protracted
withdrawal and early abstinence craving (1064).
Studies in Europe have evaluated patients who have generally
started on the medication while in a hospitalized setting and who
were abstinent for at least 7–10 days before taking the
medication; the results of those studies showed that an increased
number of patients maintain abstinence. Those who relapsed had more
abstinent time before their first drinking day and also more overall
abstinent days during a year or more of treatment (1062, 1063, 1065, 1066). In contrast, a multisite trial completed in the United States
did not find acamprosate to be effective in a primary intent-to-treat
analysis but did find that when subjects' motivation to
maintain abstinence and adhere to medication treatment was taken
into account, acamprosate was more effective than placebo in increasing
the number of abstinent days (1067). The U.S. trial included outpatients
who had a varied number of abstinent days prior to medication initiation,
but, in general, the overall pretreatment abstinent time was much
shorter than that in the European trials. Also, subjects in the
U.S. trial received a standardized medical management type of counseling,
whereas the European studies generally used varied traditional psychosocial
alcohol treatment approaches focusing on the maintenance of abstinence.
It would appear that, although not specifically studied, a number
of days (perhaps 7 or more) of abstinence prior to starting acamprosate
might be needed for acamprosate to be most effective.
There is also some evidence that acamprosate and naltrexone
can be given together, but the benefit of doing so has not been
clearly established (954, 1068). The COMBINE Study, a multisite
trial supported by the National Institute on Alcohol Abuse and Alcoholism
is in the process of further assessing the efficacy of acamprosate
alone and in combination with naltrexone with and without a specialist-delivered
behavioral intervention (1069, 1070). Acamprosate has also been
studied in combination with disulfiram and has shown an apparent
improvement in efficacy (1071).
At a dosage of two 333-mg pills t.i.d. (total dose of 1,998
mg), which is an approved dose in the United States, acamprosate
is well tolerated, with generally self-limited and symptomatically
treated diarrhea being the main adverse effect. Because acamprosate
is excreted by the kidneys and not metabolized by the liver, caution
must be taken with patients who have renal impairment (1072). However,
liver disease should not affect its metabolism or blood level concentrations.
Acamprosate has minimal if any negative interaction with alcohol
so that it is expected to be generally safe in active or relapsed
drinkers.
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d) Medications acting
on the serotonin system
SSRIs have been used in the treatment of alcoholism to directly
affect alcohol consumption, with the goal of reducing drinking or
promoting abstinence. SSRIs also may reduce psychiatric symptoms
or syndromes (e.g., anxiety, depression) that might influence drinking
behavior.
In addition to evidence that serotonin modulates the behavioral
effects of alcohol (479, 1073–1075), several randomized,
double-blind, placebo-controlled human studies with nondepressed
heavy drinkers found that SSRIs reduce short-term alcohol consumption
by 15%–20% (1076, 1077). However, subsequent
studies in patients diagnosed with alcohol dependence have been
less consistent (1078–1080) and suggest that SSRIs may
worsen drinking behaviors in some individuals. The use of SSRIs
in the treatment of alcohol dependence is similar to their use in
other disorders (430), although gastrointestinal side effects may
be more prominent in alcohol users.
TCAs also have nonselective effects on serotonin reuptake
and have been used to treat depression associated with alcohol use
disorders with equivocal results (138). However, two studies showed
improved mood and reduced alcohol consumption in open (428) and double-blind,
placebo-controlled trials (1081) with desipramine. Subsequent randomized, double-blind,
controlled trials with desipramine (438) and imipramine (437), as
well as a recent meta-analysis (425), concluded that TCAs may offer
modest benefits in treating patients with alcohol use disorders
and depression but not those with alcohol use disorders in the absence
of depression.
Based on animal studies (1082, 1083) and early clinical laboratory
findings (1084), the selective serotonin-3 receptor antagonist ondansetron
was thought to have effects on alcohol reward and thereby reduce
alcohol consumption and promote abstinence. Although patients with
early-onset alcoholism and lower levels of drinking showed some
benefit with low-dose ondansetron (1085, 1086), other patient subgroups
did not demonstrate a response. Replication studies have yet to
be conducted, and ondansetron is not approved by the FDA for alcoholism
treatment. (Dosing, side effects, and implementation of treatment with
ondansetron are discussed in greater detail in Section IX.B.3.d.)
The use of lithium to treat patients with an alcohol use disorder
not comorbid with bipolar disorder was supported by some early anecdotal
reports and by a small double-blind, placebo-controlled study (1087).
However, a large VA collaborative study (1088) showed no benefits
of lithium over placebo for patients with or without depressive
symptoms. A more recent meta-analysis also showed no efficacy for
lithium in treating alcohol use disorders (1036). Consequently,
lithium is not recommended as a primary treatment in patients who
do not have co-occurring bipolar disorder.
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D. Psychosocial Treatments
A variety of psychosocial treatments have been used in the
treatment of alcohol use disorders (1089), and the efficacy of specific
psychotherapies for these disorders has been reviewed by a number
of authors (79, 956, 1090, 1091). The sections that follow provide
an overview of the use of CBT, behavioral therapies, psychodynamic
therapies, IPT, self-help groups, brief interventions, marital and
family therapy, and aftercare in the treatment of alcohol use disorders.
+
1. Cognitive-behavioral
therapies
CBT and relapse prevention therapies aimed at improving self-control
and social skills have been consistently found to reduce drinking
(79, 1090, 1092–1094); such cognitive-behavioral therapies,
as well as MET and TSF, are therefore recommended for use in individuals
with an alcohol use disorder. Cognitive-behavioral stress management
interventions and behavioral self-control training (consisting of
cognitive and behavioral strategies, including self-monitoring,
goal setting, rewards for goal attainment, functional analysis of drinking
situations, and the learning of alternative coping skills) produced
better outcomes than control treatments in about half of the studies
(79, 1090, 1095–1097). Better outcomes during follow-up
also seem to occur in individuals who show increased coping responses or "self-efficacy" at
the end of treatment (184, 1098–1100) and in those who
use problem solving or mastery rather than relying on avoidance
of high-risk situations as a coping strategy (43, 265, 959, 1101).
In contrast, cognitive therapy interventions that are focused on identifying
and modifying maladaptive thoughts but that do not include a behavioral
component are not as effective.
In group settings, CBT approaches are similarly effective,
although treatment benefits may vary with patient characteristics
(1102–1104). Finally, most studies show efficacy for social
skills training, which focuses on learning skills for forming and
maintaining interpersonal relationships, being assertive, and refusing
alcohol (79).
MET and motivational interviewing are typically brief therapies
that last one to four sessions and are aimed at maximizing the patient's
intrinsic desire to change or enhancing a patient's adherence
to more intensive or extended treatment. Motivational approaches
have been found to be efficacious in most studies (reviewed by Dunn
et al. [1105] and Miller and Wilbourne [79]),
including the findings from Project MATCH (43, 90, 265, 1106) in
which four MET sessions given as a stand-alone treatment either
initially or as part of posthospitalization care were comparable
to 12 sessions of CBT or TSF, with benefits of treatment persisting
through 3 years of follow-up.
+
2. Behavioral therapies
Individual behavioral therapy, particularly involving positive
reinforcements for targeted behaviors, has been found to be effective
for patients with an alcohol use disorder (191, 956, 1090) and is
also a recommended treatment approach. Also effective are behavioral contracting
(79) and the community reinforcement approach (190, 1107, 1108),
which uses behavioral principles and usually includes conjoint therapy,
training in job finding, counseling focused on alcohol-free social
and recreational activities, monitoring of disulfiram use, and an
alcohol-free social club. When compared with usual outpatient treatment
or disulfiram plus a behavioral adherence program, community reinforcement
led to significantly better patient outcomes (190, 1108). Community
reinforcement also has documented effectiveness in combination with
marital therapy (690). Compared with positive reward approaches,
aversive therapies have been less successful (79). Relaxation training,
although widely studied, has been ineffective in virtually all controlled
trials (79).
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3. Psychodynamic
and interpersonal therapies
There are insufficient studies of adequate research design
regarding the use of group or individual psychodynamically oriented
psychotherapies for the treatment of individuals with an alcohol
use disorder (79, 1090). It is difficult to draw conclusions in
this area because of the paucity of well-controlled and designed
studies, and the small extant literature is limited by poor research
design and short duration of studies. However, there is some clinical
consensus that such treatment is particularly helpful when other
psychiatric disorders or interpersonal issues are present and when
combined with other psychosocial or biological interventions. There
are large numbers of patients in this type of treatment, and clinical
consensus suggests the therapy is effective in at least some of
these patients (956, 1090). In addition to addressing alcohol abuse
or dependence, treatment goals often include stabilization of the
patient's social and interpersonal life, disorganization
of which may both accompany and perpetuate the alcohol use disorder.
Brief interventions are generally delivered over one to three
sessions and include an abbreviated assessment of drinking severity
and related problems as well as the provision of motivational feedback
and advice. Typically studied in general medical or school-based settings
and in non-treatment-seeking heavy drinkers, brief therapies have
been shown to be effective in reducing alcohol use and improving
general health and social functioning (79, 275, 1109). In these
subgroups of patients, the efficacy of brief therapies is often
comparable with that of longer, more intense treatment; even very
brief interventions (i.e., a few hours) may have some positive effect
(1110, 1111).
+
5. Self-help groups
and 12-step-oriented treatments
The effectiveness of AA, per se, has not been evaluated in
randomized studies. However, other sources of information provide
growing support for the utility of AA and 12-step-oriented treatments
(259, 261, 956, 958, 959) as well as the efficacy of professional
therapies such as TSF that are aimed at motivating patients to participate
in AA (43, 219, 265, 267, 269). In addition, a large number of studies
have documented that greater AA participation is associated with
greater rates of abstinence from alcohol (1112) as well as with
better drinking outcomes (260–266, 289, 1113, 1114). Thus,
most patients should be encouraged to attend at least several AA
meetings to ascertain the appropriateness and utility of AA in helping
them remain alcohol free. Individual patient needs and concerns
should, however, be taken into consideration when making this recommendation.
As a spiritual but nonreligious program requiring belief in
something beyond oneself (268), AA provides tools for its participants
to maintain sobriety, including the 12 steps, group identification,
and mutual help. More specifically, "AA is a fellowship
of men and women who share their experience, strength and hope with
each other that they may solve their common problem and help others
to recover from alcoholism. The only requirement for membership
is a desire to stop drinking" (253). Al-Anon (friends and
family), Alateen (teenage children of alcoholic individuals), and
Adult Children of Alcoholics (those who grew up in alcoholic or
otherwise dysfunctional homes) help family members and friends of
alcoholic individuals focus on the need to avoid enabling behaviors
and care for oneself whether a loved one is drinking or not. Other
mutual help programs include Women for Sobriety, Rational Recovery,
Double Trouble (for patients with alcohol dependence comorbid with
other psychiatric disorders), and Mentally Ill Chemical/Substance
Abusers.
Patients may be more likely to benefit from AA groups composed
of individuals with similar personal characteristics, such as age,
sex, or cultural and occupational status. Evidence from small-scale
trials on patient-to-program matching suggests that patients with
a greater severity of drinking problems, an affective rather than
cognitive focus, a concern about purpose and meaning in life, better
interpersonal skills, and a high need for affiliation are good candidates
for AA (254, 1115). In the landmark Project MATCH study (43), TSF-based
aftercare was more effective than that using CBT for outpatients
who did not show psychiatric symptoms and was of comparable efficacy
for those with psychiatric symptoms. At 1-year follow-up, patients
rated as high in seeking meaning of life fared better with TSF compared
with MET and CBT, and patients with high social support for abstinence
had better drinking outcomes at 1- and 3-year follow-up.
Although official AA policy encourages members to adhere to
medical treatment, many individual members interpret the ethos of
coping without the use of drugs to mean that recovering individuals
should also forgo psychiatric medications (1116). Consequently,
patients with a co-occurring psychiatric disorder requiring medication
should be encouraged to attend dual-diagnosis AA groups or those
in which regular attendees do not oppose medically prescribed psychotropic
treatment.
+
6. Marital and family
therapies
For patients who are married or living with family members,
such relationships can be an important factor in the posttreatment
environment (1090, 1117). Thus, it is not surprising that therapies
aimed at enhancing marital or family relationships can be effective
in the treatment of alcohol use disorders. In particular, behavioral
marital therapy has demonstrated efficacy and cost-effectiveness
(79, 225, 236, 238, 690, 961, 1118, 1119). Marital approaches for
which there is significant support are Al-Anon facilitation and
disulfiram contracting (168, 248); other approaches to marital therapy
have shown lesser degrees of efficacy (79).
+
7. Self-guided therapies
Strong evidence is available to support the efficacy of self-monitoring
of drinking patterns, guided by pamphlets provided by practitioners
(79). Such approaches have typically been evaluated in general populations
of primary care patients or with heavy drinkers who do not meet
full criteria for alcohol dependence. Patients presenting to specialized
substance use disorder treatment settings have generally experienced
multiple failures at self-treatment and are poorer candidates for
this approach.
A patient's involvement in aftercare after completing
inpatient treatment for an alcohol use disorder is an important
predictor of outcome (264, 1120, 1121). The lowest rates of relapse
have been noted in those completing an aftercare program (1121, 1122), with some evidence that completion rates vary with therapists' efforts
to maintain patients in the aftercare program (1122). Although the
number of trials on specific aftercare approaches is limited, there
is evidence for efficacy for TSF (43, 265), MET (43, 265), CBT administered alone
(43, 265) or with coping skills training (223, 1102, 1103), a version
of behavioral marital therapy that includes relapse prevention techniques
(1118, 1119), insight-oriented interactional group therapy (223, 1102, 1103), and nurse visits delivered over a 12-month period (1123).
+
E. Clinical Features
Influencing Treatment
The treatment implications of various clinical features are
summarized in Section II.G. In addition to these considerations,
specific sequelae and patterns of co-occurring disorders need to
be considered for patients with an alcohol use disorder.
+
1. Co-occurring psychiatric
disorders
Co-occurring psychiatric disorders are common among individuals
with an alcohol use disorder. Integrated psychosocial treatments
that combine traditional therapies for the psychiatric condition
with therapies for the alcohol use disorder have been shown to be
effective (376, 1124, 1125). In general, medications recommended
to treat patients with an alcohol use disorder alone are also effective
in patients with a co-occurring psychiatric disorder, and pharmacological
treatment of the psychiatric disorder is similar to that recommended
when the psychiatric disorder occurs independently of an alcohol
use disorder. Some exceptions to these general principles are discussed
below.
Given the propensity of individuals with alcohol and other
substance use disorders to misuse prescribed medications, the treating
clinician should give preference to prescribing medications that
have a low abuse potential. Patients with a high level of depression,
impulsivity, or poor judgment or the potential for making a suicide
attempt should receive medications with a low potential for lethality
in overdose (e.g., SSRIs) (1126, 1127). Given the tendency of patients
with co-occurring disorders to have poor medication adherence and an
increased risk of overdose, medications should be dispensed in limited
amounts, the number of refills should be limited, and random or
frequent blood or urine toxicology screening should be used to determine
use of both prescribed and nonprescribed medications.
Many patients with alcohol dependence present with signs and
symptoms suggestive of major depression or an anxiety disorder.
In many patients, however, these signs and symptoms are related
to alcohol intoxication or withdrawal and remit in the first few
weeks of abstinence (424). Consequently, many psychiatrists feel
that patients should be observed over a 3- to 4-week substance-free
period before a diagnosis of a co-occurring mood or anxiety disorder
is made and a disorder-specific medication is prescribed. Others
suggest that in selected cases, earlier initiation of treatment
is warranted. For example, depressed patients with particularly
severe symptoms, a history of major depression unrelated to periods of
alcohol use, and/or a strong family history of mood disorders
are more likely to have a co-occurring depression that should be
treated soon after detoxification is completed (426–429).
Although studies of SSRIs in individuals with an alcohol use
disorder who are not depressed have shown mixed benefit (see Section
IV.C.3.d), studies of those who are depressed have shown a moderate
positive effect on the patients' addiction and mood (431, 1128, 1129). TCAs may also be effective for alcohol-dependent patients
with comorbid depression (425, 437, 438), although the risk of poor
adherence, tricyclic-to-alcohol interactions, and overdose should
be considered with such patients. In addition, tricyclic plasma levels
may be lower than expected because of the alcohol-induced increase
in liver microsomal oxidases (1130, 1131). MAOIs have been used
to treat patients with atypical depression, but there is a high
risk of poor adherence to dietary and medication restrictions (including
those for alcohol) and subsequent adverse reactions (e.g., hypertension)
in patients with alcohol use disorders (1132). Consequently, because
SSRIs and other nontricyclic, non-MAOI antidepressants have fewer
adverse effects and less risk of morbidity and mortality in overdose
situations, they are preferred over tricyclic and MAOI antidepressants
in the treatment of patients with a co-occurring alcohol use disorder
and depression (1133).
Studies of antidepressant agents in individuals with an alcohol
use disorder and co-occurring anxiety are limited (1134). Consensus
would suggest that these medications can be used as recommended
for patients with an anxiety disorder alone.
The use of benzodiazepines for alcohol-dependent patients
with comorbid anxiety or panic disorder is more controversial, as
benzodiazepines have a high abuse potential in these patients. For
patients with generalized or performance anxiety, beta-blockers
(e.g., propranolol) and buspirone are preferable to benzodiazepines
because they have no cross-tolerance with ethanol or other CNS depressants
and minimal abuse potential. Buspirone has also been reported to
reduce alcohol consumption in patients with high levels of comorbid
anxiety (479, 1135). In patients with otherwise treatment-resistant
panic disorder, clonazepam or other long-acting benzodiazepines
can be cautiously administered if the principles outlined in Section
II.G.2.d.2.d. are observed.
For patients with comorbid bipolar and alcohol use disorders,
lithium, valproate, or carbamazepine may be used. A recent double-blind,
controlled study of patients with bipolar disorder and alcoholism
who were being maintained with valproate showed promising results
of this medication as an adjunct to treatment (472). However, when
prescribing lithium, valproate, or carbamazepine, the clinician
may need to closely monitor the patient for side effects. In particular,
the low therapeutic index of lithium may lead to a greater risk
of toxicity in individuals with an alcohol use disorder who are
actively drinking, and hematological abnormalities may be more pronounced
in alcohol-dependent individuals who are treated with valproate
or carbamazepine.
In patients with schizophrenia, some data suggest that clozapine
may be useful for treating the symptoms of both schizophrenia and
a comorbid substance use disorder, including an alcohol use disorder
(384, 391, 393, 398), a possibility that requires further study
in double-blind, randomized, controlled trials.
+
2. Comorbid general
medical disorders
Chronic high-dose alcohol use can affect several different
organ systems, including the gastrointestinal tract, the cardiovascular
system, and the central and peripheral nervous systems. Alcohol-induced
gastrointestinal problems include gastritis, ulcers of the stomach
or duodenum, esophageal varices, portal hypertension, and, in approximately
15% of heavy users, cirrhosis of the liver and pancreatitis
(1136–1138). Alcohol-dependent individuals also experience
higher-than-average rates of cancer of the esophagus, stomach, and
other parts of the gastrointestinal tract (1139, 1140).
Common comorbid cardiovascular conditions include low-grade
hypertension and increased levels of triglycerides and low-density
lipoprotein cholesterol, which increase the risk of heart disease.
Cardiomyopathy occurs primarily among very heavy drinkers (1141).
For men, endocrinological changes associated with chronic
alcohol use include decreases in testosterone, loss of facial hair,
breast enlargement, decreased libido, and impotence (1142); endocrinological
changes for women include amenorrhea, luteal phase dysfunction,
anovulation, early menopause, and hyperprolactinemia (1143). Blunting
of the thyroid-stimulating hormone response to thyrotropin-releasing
hormone, hypoglycemia, ketosis, and hyperuricemia have also been
reported (1144, 1145).
Alcohol-induced peripheral myopathy with muscle weakness,
atrophy, tenderness, and pain is accompanied by elevations in creatine
phosphokinase levels and the presence of myoglobins in the urine
(1146). Histological evidence of myopathy can be observed in a significant
proportion of patients with an alcohol use disorder, even in the
absence of symptoms (1147). When it is severe, alcohol-induced myopathy
can involve rapidly progressive muscle wasting.
Many patients seeking treatment of alcohol dependence manifest
cognitive abnormalities (1148–1150). Chronic, heavy drinkers
can experience an alcoholic dementia with characteristic cognitive
deficits that include impairment in short- and long-term memory, abstract
thinking, judgment, and other higher cortical functions as well
as personality change. Usually the memory deficits are less severe
than in Korsakoff's syndrome (alcohol-induced persisting
amnestic disorder) or Alzheimer's disease (1151). Neuropathological
abnormalities in the frontal lobes, in the area surrounding the
third ventricle or diffusely through the cortex, have been reported.
More commonly, however, there is subtle cognitive dysfunction that
hampers a patient's ability to comprehend or adhere to
a treatment plan (1148, 1149, 1152, 1153). For such patients, family
members or other responsible parties should be actively involved
from the beginning of and throughout the course of treatment. Initial
placement of the patient in a more structured (e.g., residential)
treatment setting may also be indicated to assess the impact of
cognitive problems on the patient's ability to adhere to
short- and long-term treatment. In patients who remain abstinent,
reversal of alcohol-induced cognitive disturbance is often observed
over time (1154, 1155).
Other nervous system sequelae of chronic alcohol use, including
peripheral neuropathies, degenerative changes in the cerebellum,
Wernicke's encephalopathy, and Korsakoff's syndrome,
are related to vitamin deficiencies, particularly deficiencies in
thiamine and other B vitamins (1156). Peripheral neuropathy is common,
occurring in up to 33% of hospitalized individuals with
an alcohol use disorder, with an even greater proportion of alcohol users
showing electrophysiological evidence of peripheral nerve damage
(1157). Symptoms of alcoholic neuropathy typically include sensory
loss, paresthesias, a burning sensation of the feet, numbness, cramps,
weakness, calf pain, and ataxia. Ataxia in alcohol-dependent patients
can also occur due to cerebellar dysfunction.
Wernicke's encephalopathy is characterized by ophthalmoplegia,
ataxia, and confusion (972, 1158). Ocular abnormalities include
nystagmus, eye muscle palsies, and pupillary abnormalities. The
mortality rate for acute untreated Wernicke's encephalopathy
is 15%–20% (1159, 1160); recovery is
incomplete in 40% of cases. Most patients (approximately
80%) with Wernicke encephalopathy also develop Korsakoff's
syndrome, characterized by anterograde and retrograde amnesia, disorientation,
poor recall, and impairment of recent memory coupled with confabulation.
Lesions in the mammillary bodies and thalamic nuclei may be the
result of vitamin deficiencies or the direct toxic effects of alcohol.
Recovery is variable and not possible to predict on the basis of
brain imaging. In more than half of the patients, elements of Korsakoff's
syndrome are permanent.
These neurological complications should be treated vigorously
with B complex vitamins (e.g., thiamine, 50–100 mg/day
i.m. or i.v.), usually after adequate fluids and glucose levels are
maintained. Some patients may require treatment with B complex vitamins
over a prolonged period, and improvements may continue to occur
up to 1 year after treatment is begun (1161).
Alcoholic hallucinosis during or after cessation of prolonged
alcohol use may respond to antipsychotic medication. Unlike the
visual hallucinations that may occur during alcohol withdrawal,
these are primarily auditory and occur in conjunction with a clear
sensorium (1162).
The general effects of substance use during pregnancy are
described in Section II.G.4. Alcohol-related disorders may have
specific adverse effects on the health of the pregnant woman, the
course of the pregnancy, fetal and early child development, and
parenting behavior. The most well-established effect of in utero
alcohol exposure is fetal alcohol spectrum disorder (587, 1163 ,1164).
Some children with this disorder will exhibit the characteristic
features of fetal alcohol syndrome, including low birth weight,
poor coordination, hypotonia, neonatal irritability, retarded growth
and development, craniofacial abnormalities (including microcephaly),
cardiovascular defects, mild to moderate retardation, childhood
hyperactivity, and impaired school performance (586, 972, 1165, 1166). Others will not have the classically described features of
fetal alcohol syndrome but will exhibit cognitive and behavioral
effects of in utero alcohol exposure (587, 1163, 1164). Thus, the goals
in treating pregnant women with an alcohol use disorder include
eliminating the use of alcohol, treating any comorbid psychiatric
or general medical disorders, guiding the patient safely through
the pregnancy, facilitating appropriate parenting behavior, and
motivating the patient to remain in treatment after delivery to
minimize the risk of relapse.
+
VII. Treatment of
Opioid-Related Disorders
According to the 2003 National Survey on Drug Use and Health
(1191), there were approximately 3.7 million lifetime users of heroin
in 2003. Of these lifetime users, 314,000 individuals had used heroin
in the previous year and 169,000 reported heroin dependence at some
point in the previous year. This suggests that a high proportion
(54%) of individuals who used heroin in the previous year
were dependent on this opiate. These numbers are likely to be significant
underestimates because of the difficulty in ascertaining community rates
of heroin dependence; the Office of National Drug Control Policy
estimates that 750,000 to 1,000,000 individuals are heroin dependent
(1333a).
Heroin is not the only opiate that is abused; there has been
a growing awareness of misuse or "nonmedical use" of
prescription pain relievers (e.g., hydromorphone, morphine, oxycodone,
codeine, propoxyphene). The 2003 survey found that there were approximately 31.2
million individuals who reported nonmedical use of prescription
pain relievers in their lifetime, a rate markedly higher than the
rate of lifetime heroin use. Approximately 11.7 million reported
using opiates for nonmedical reasons in the previous year, and 943,000
individuals fulfilled criteria for opioid dependence that same year.
Although a considerably lower proportion of individuals with past-year
use were dependent on prescription opioid pain relievers compared
with heroin (8% vs. 54%), it is important to note
that over five times as many individuals are dependent on prescription
opioid pain relievers than on heroin.
Given the number of individuals who are using and are dependent
on opiates, it is not surprising that the most commonly studied
substance-related conditions, and those for which treatments have
been most extensively studied, are opioid dependence, opioid abuse, opioid
intoxication, and opioid withdrawal. Treatment for opioid-related
conditions can be highly effective. Interventions include pharmacological
treatments with agents such as methadone, buprenorphine, and naltrexone
and nonpharmacological services such as behavioral therapies and
counseling. The treatment of opioid dependence, in particular, is
one of the most extensively researched areas in the field of addictions,
and the range of available treatments is more extensive than for
most other substance use disorders.
Despite the number of effective treatments for opioid dependence
and the scientific basis for their efficacy and safety, the availability
of treatment programs for this and other illicit drug use is limited.
Among the multiple factors that probably contribute to the limited availability
of such treatment generally and opioid dependence treatment in particular
are the social stigma associated with treatment facilities and their
patient population, limited funding for treatment, and a history
of variability in the quality of treatment supplied by clinicians
and existing programs. In addition, social ambivalence about the
nature of addictions and the medicalization of substance use disorder
treatment may be significant contributing factors for the difficulty
of expanding such treatment.
There are two general thoughts regarding the treatment goals
for patients with an opioid use disorder: 1) there should be abstinence
from all illicit opioid use or 2) there should be a substantial
decrease in use but abstinence is not an absolute requirement. The
logic of the latter is that decreased use of illicit substances
will translate into lower rates of risky behavior and that this
is a worthy goal of treatment. Although these two general goals
may seem opposed, it may be helpful to conceptualize the latter
as an acceptable intermediate stage toward the ultimate achievement
of the first goalabstinence.
Additional goals of treatment include addressing other substance
use, psychosocial outcomes (e.g., impact of drug use on employment,
reconciliation with family members), and psychiatric and somatic
needs (e.g., treatment for comorbid affective disorders, management
of chronic physical disorders). Treatment goals will vary depending
on the circumstances of the particular patient, the specific opioid-related
disorder for which the patient seeks treatment, the treatment setting,
the resources available to the practitioner, and the resources available
to the patient.
Defining specific goals that are applicable to all patients
is unrealistic, but a few further general points regarding treatment
goals are worth noting. For example, cessation or stabilization
of substance use should be an early and primary treatment goal.
It is probably premature to attempt to rectify many early psychiatric
symptoms or psychosocial problems while a patient is actively using
opioids. However, exceptions may be made in certain circumstances,
such as with a patient who has a clear history of a psychiatric
disorder that is independent of the substance use or a patient who
is acutely suicidal. In particular, the patient who maintains that
he or she needs pharmacological treatment for anxiety or depressive
symptoms to control illicit opioid use is probably best initially
managed with a focus on the substance use. Another general treatment
goal may include educating patients about the possibility of relapses
during treatment and the importance of making a plan to prevent further
substance use if a relapse occurs. Finally, treatment expectations,
such as the patient's behavior (e.g., tardiness, missed
appointments, presenting while intoxicated) and the clinician's
responsibilities (e.g., providing emergency contact information,
providing other resources to optimize outcomes) are related to treatment
goals and may be addressed through a discussion with the patient.
In general, there are five settings or modalities in which
most treatment of opioid-related disorders occurs: inpatient hospital
settings, outpatient clinics and offices, opioid treatment programs,
self-help programs, and therapeutic communities. The choice of treatment
setting depends on the clinical characteristics and preferences
of the patient, the patient's perceived treatment needs,
and the available alternatives. As in the treatment of all patients, the
least restrictive setting that is likely to facilitate safe and
effective treatment is preferred.
There are some general guidelines and recommendations for
treatment settings for opioid-related disorders. An opioid overdose,
which in severe cases can be a life-threatening emergency, should
be evaluated and initially managed in a supervised medical setting
such as an emergency department or inpatient service. Treatment
typically includes reversal of opioid effects with an opioid antagonist
(e.g., naloxone). Opioid withdrawal may also be treated in an inpatient
setting and can be effectively managed with pharmacological agents such
as opioid agonist medications (e.g., methadone, buprenorphine) or
nonopioid medications (e.g., clonidine). Although management of
opioid withdrawal symptoms can be effectively achieved relatively
quickly in an inpatient setting (i.e, within 7 days), long-term outcome
for such withdrawal is generally poor, with high rates of relapse
after discharge from the controlled setting. Continued treatment
for the opioid use disorder after withdrawal is indicated in most
cases. Inpatient opioid withdrawal without specific outpatient follow-up
(e.g., drug-free treatment) is an inadequate intervention that has
a low likelihood of long-term success.
The second possible setting is outpatient clinics and offices.
This can include so-called drug-free programs (treatment programs
that do not provide opioid agonist medications to the patient),
group practices, and the individual practitioner's office.
Drug-free programs can provide services to patients who have undergone
an inpatient, medically supervised opioid withdrawal. Although these
programs do not provide opioid agonists to patients, they may provide
naltrexone for the treatment of opioid dependence. Group practices
and the individual practitioner's office may provide buprenorphine
or naltrexone for the treatment of opioid dependence. The Drug Addiction
Treatment Act of 2000 allows physicians in the United States to
prescribe schedule III, IV, and V medications that are approved
for the treatment of opioid dependence from office-based settings,
although there are stipulations on this practice. Currently, sublingual
buprenorphine and sublingual buprenorphine plus naloxone are the
only FDA-approved agents for this purpose. There also has been interest
in developing office-based methadone treatment, which is generally
not available in the United States except under certain circumstances
in which a physician works with an opioid treatment program (1334).
Outpatient opioid treatment programs, a third treatment setting,
are primarily methadone maintenance programs, although buprenorphine
can also be provided in this setting. These operate under special
federal and state regulations, and expansion of this modality has
been difficult in many parts of the United States. However, when
properly operated, these programs can be highly effective for patients
who have been unable to maintain abstinence from illicit opioid
use. Methadone maintenance is the most common form of pharmacological
treatment for opioid dependence, with more than 240,000 individuals
estimated to be receiving methadone treatment in the United States
in 2004. Routine office-based pharmacological treatment with buprenorphine,
and possibly methadone, in the future has considerable promise based
on research studies and the growing clinical experience with this
form of treatment in the United States. Experience from France (1334a)
suggests these treatments can substantially reduce opioid-related
mortality, but there is a risk of buprenorphine diversion to other
uses and abuse in the outpatient setting.
Self-help programs such as Narcotics Anonymous are another
form of treatment used by individuals with opioid abuse or dependence.
Because anonymity is an integral part of these programs, it is difficult
to know the extent of their utilization, outcomes achieved, or factors that
predict a particular person's success in such programs.
However, anecdotal reports from patients and the pervasive availability
of the meetings suggest these programs serve a valuable function
and are effective for many people who have used illicit opioids.
Self-help groups can also be effective when used within the different
treatment settings previously discussed (see Section II.F.8).
Therapeutic communities are yet another treatment setting
for patients who abuse or are dependent on opiates (see Section
II.C.2.d). Therapeutic communities can be an effective treatment
for some patients with opioid dependence but have decreased in prominence
over time. However, there is renewed interest and evidence of efficacy
for therapeutic communities in special circumstances, such as with
criminal justice populations.
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1. Treating dependence
and abuse
+
a) Full mu agonist
therapy: methadone and LAAM
There are two approved full mu agonist opioid medications
available for the treatment of patients with chronic and relapsing
opioid dependence: methadone and LAAM, both schedule II medications.
Methadone is the most thoroughly studied and widely used pharmacological
treatment for opioid dependence (1335, 1336). It is orally active,
can be dosed once per day, and at sufficient doses does suppress
opioid withdrawal and block the effects of other opioids. LAAM is
structurally related to methadone and shares many similar features
(oral activity, withdrawal suppression, blockade effects) but has
a longer duration of action, allowing dosing on a less than daily
basis. Although it is still an FDA-approved medication, LAAM has
been withdrawn from the United States market by its manufacturer because
of an associated risk of cardiac arrhythmias (1337).
Each of these medications is available only through specially
licensed opioid treatment programs. Oversight of these programs
was recently shifted from the FDA to SAMHSA, and the programs are
now accredited by an outside agency such as the Joint Commission on
Accreditation of Healthcare Organizations. Many of the prior treatment
regulations have been revised (including greater flexibility in
take-home doses of medication).
The primary goals of opioid agonist maintenance treatment
are to 1) achieve a stable maintenance dose that suppresses withdrawal,
reduces opioid craving, blocks the effects of illicit opioids, and
eventually stops illicit opioid use; and 2) facilitate patient engagement in
a comprehensive program designed to prevent dependence or abuse
of other substances and promote rehabilitation.
The choice of treatment for opioid dependence is based on
patient preference, assessment of the patient's past response
to treatment, the probability of the patient's achieving and
maintaining abstinence for the different treatment modalities, and
the physician's assessment of the short- and long-term
effects of continued use of illicit opioids on the patient's
life adjustment and overall health status. Because methadone maintenance
may become a lifelong therapy, some physicians prefer to avoid it
as a first-line treatment for opioid dependence in adolescents.
In addition, the higher demand versus availability of opioid treatment
programs can be an additional and significant factor influencing
referral to this type of program.
Methadone maintenance treatment for opioid-dependent individuals
has generally been shown to be effective in 1) decreasing illicit
opioid use, 2) decreasing psychosocial and general medical morbidity
associated with opioid dependence, 3) improving overall health status,
4) decreasing mortality, 5) decreasing criminal activity,
and 6) improving social functioning (171, 1338–1340). Several
studies also support the usefulness of methadone maintenance in
reducing the spread of HIV infection among intravenous drug users
(1341). It should be noted that methadone maintenance treatment
involves a combination of methadone medication and nonpharmacological
services. The latter can include individual and group counseling,
urine testing, and behavioral treatments, with the purpose of addressing opioid
and other substance use as well as the psychosocial problems associated
with drug use. Further discussion of psychosocial treatments for
opioid-related disorders is provided in Section VII.D.
One of the key issues in methadone maintenance is determining
a dose sufficient to suppress the patient's opioid withdrawal
and craving, as no single dose is optimal for all patients. Some
may benefit from maintenance on lower doses such as 
40 mg/day,
whereas others may require >100 mg/day to achieve maximum
benefit. Controlled studies of methadone dosing have not tested
daily doses of >100 mg/day, although there are anecdotal
reports of such use in the United States, and doses greater than
100 mg/day are used in several other countries (1342–1346).
Although 40–60 mg/day of methadone (and sometimes
less) is usually sufficient to block opioid withdrawal symptoms (1339),
higher doses are usually needed during maintenance treatment to
block craving for opiates and associated drug use. Higher doses
of methadone are also generally needed for heroin addicts with axis
I psychiatric comorbidity (1347, 1348). In general, higher doses are
associated with better treatment retention and lower rates of illicit
opioid use (1349–1352).
Maintenance on methadone is generally safe. Methadone undergoes
hepatic metabolism by CYP 450 3A4 in conjunction with other P450
enzymes; its half-life is approximately 24 hours, so methadone can
be administered once daily (1353). However, other concurrent medications
and/or substances of abuse that a patient might be taking
need to be considered because they may induce symptoms of withdrawal,
toxicity, and even death by interfering with the metabolism of methadone
(1354, 1355). The most common side effects of methadone are constipation,
increased sweating, and sexual difficulties. Although early studies of
methadone found the medication had no significant effect on cognition
or performance measures (1356–1358), other studies have
found evidence of some subtle but significant effects (1359, 1360).
Finally, overdose with methadone or any mu agonist can produce respiratory
depression and death. Methadone can be used as an analgesic, and
there has been evidence of increased methadone-related deaths as
the frequency of prescribing methadone for pain management has increased.
Methadone can be diverted for abuse, as can other opiates that have
agonist effects at the mu receptor (e.g., LAAM, buprenorphine).
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b) Partial mu agonist
therapy: buprenorphine
Buprenorphine is a mixed opioid agonist-antagonist with a
pharmacological profile different from that of full mu agonists
such as methadone. Buprenorphine produces a less than maximal or
partial agonist effect at the mu receptor (its primary action with
respect to the treatment of opioid dependence) and an antagonistic
effect at the kappa receptor (126). These receptor interactions
are thought to account for buprenorphine's unique profile
of effects, which have clinical implications for treating opioid
dependence.
Buprenorphine has been marketed worldwide as a parenteral
analgesic for many years. Because it has poor oral but fair sublingual
bioavailability, a sublingual buprenorphine tablet has been developed
for the treatment of opioid dependence. Buprenorphine enters the bloodstream
more slowly through the sublingual route than with parenteral administration and
thus has less abuse potential compared with the parenterally delivered
form. There are two forms of the sublingual tablet: a buprenorphine-only
tablet and a combination tablet of buprenorphine and the opioid
antagonist naloxone. Because naloxone has poor sublingual but good
parenteral bioavailability (1361), it is hoped that the combination
tablet may decrease the risk of buprenorphine diversion to other
uses and parenteral abuse even further because naloxone used parenterally
will precipitate opioid withdrawal in opioid-dependent patients.
Both forms of buprenorphine tablets are schedule III medications
in the United States.
Like methadone, buprenorphine can suppress opioid withdrawal
and block the effects of other opioids. Clinical trials comparing
daily sublingual buprenorphine (equivalent of 12–16 mg
of the tablet form per day) to moderate doses of daily oral methadone
(i.e., 50–60 mg/day) have generally shown comparable
outcomes on treatment retention and decreased illicit opioid use
(1251). However, higher doses of methadone (80 mg/day) appear
to produce superior outcomes to daily buprenorphine (1250, 1251, 1336, 1362–1364). It is not known if comparable effects could
be produced by increasing the dose of buprenorphine; current evidence
suggests buprenorphine may be best suited for patients with mild
to moderate levels of physical dependence. Nonpharmacological treatment
in combination with buprenorphine can help to achieve abstinence.
For example, a study by Galanter et al. (1365) demonstrated that
psychosocial support (in this study, network therapy) tailored to
promoting abstinence from illicit opioids during buprenorphine maintenance
can improve clinical outcomes.
Buprenorphine has a long duration of action and can be dosed
on a less than daily basis. When used in this way, the dose administered
should be increased to compensate for the longer between-dose interval
(for example, doubling the daily dose for a 48-hour interval and
tripling the daily dose for a 72-hour interval). Between-dose intervals
of 48–72 hours are generally well tolerated in most patients;
some patients may tolerate even longer intervals, such as 96 hours
(1366–1370).
In the United States, buprenorphine can be distributed not
only in special clinics but also through clinicians' offices;
access in this latter setting provides a means for expanding treatment
capacity and mainstreaming the care of opioid dependence. Daily
sublingual maintenance doses typically fall between 8 and 32 mg.
The buprenorphine-naloxone combination tablet significantly reduces
the risk the medicine will be diverted for other uses because naloxone
will exert a potent opioid antagonist effect if the combination
tablet is crushed and administered intravenously by an opioid-dependent
person. Details on use of the medication (e.g., induction, withdrawal)
are available through specific guidelines published by the Center
for Substance Abuse Treatment and through courses sponsored by professional
societies, including APA.
Buprenorphine is generally safe, and its side effects can
be similar to those seen with full mu agonist opioids. However,
in the context of abrupt cessation of opioid use, buprenorphine
is associated with a comparatively mild withdrawal syndrome (126).
Another notable difference from methadone is that overdose with
buprenorphine generally does not produce significant respiratory
depression (1371); this probably reflects buprenorphine's
partial mu agonist effects. Nevertheless, there have been reports
of fatalities when individuals overdose with a combination of buprenorphine
and a benzodiazepine, typically when both are taken parenterally.
These reports have come from France, where buprenorphine is used
extensively for the outpatient treatment of opioid dependence and
where prescribing benzodiazepines is also quite common. Finally,
there is some evidence that buprenorphine may produce mild elevations
in liver function tests, especially in individuals with a history
of liver disease. This is more likely to occur if large amounts
(greater-than-usual clinical doses) of buprenorphine are taken parenterally.
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c) Opioid antagonist
therapy: naltrexone
Naltrexone is an opioid antagonist that can be an alternative
to maintenance on full or partial mu opioid agonists. By tightly
binding to opioid receptors without producing a psychoactive effect,
naltrexone blocks the pleasurable effects of the usual street doses
of heroin and other opioids, thereby discouraging opioid use and
diminishing conditioned craving. Naltrexone cannot be given to individuals
while they are actively dependent on opioids because it can precipitate
an immediate opioid withdrawal syndrome. Before starting naltrexone,
patients must be completely withdrawn and abstinent for at least
5 days from a short-acting opioid such as heroin or 7 days from
a longer-acting opioid such as methadone. A urine toxicology screen
for opiate medication may be indicated before naltrexone therapy is
initiated. The risk of relapse during the interval between opioid
withdrawal and the initiation of naltrexone treatment is high; for
this reason, rapid opioid withdrawal, using clonidine and naloxone,
has been used to shorten the interval between withdrawal and initiation of
naltrexone treatment. Repeated doses of naloxone, a short-acting
opioid antagonist related to naltrexone, have also been used with
clonidine to shorten opioid withdrawal.
After withdrawal and the appropriate period of abstinence,
a test dose of 0.8 mg i.m. of naloxone can be used to determine
that the individual is no longer dependent on opioids before naltrexone
treatment is initiated. Naltrexone can be taken as a daily dose
of 50 mg or, because of its long duration of action, three times
per week with doses of 100 mg on Monday and Wednesday and 150 mg
on Friday. Naltrexone is approved for the treatment of opioid dependence
in the United States; it has no abuse potential and is not a scheduled substance.
Studies of naltrexone's efficacy are mixed. Although
inpatient studies of naltrexone-treated, opioid-dependent individuals
who were given the opportunity to self-administer opioids have shown
that naltrexone is highly effective at attenuating opioid use (1372),
outpatient clinical trials have failed to demonstrate a similar
robust effect (1373). Patients often drop out of such studies shortly
after completing opioid withdrawal and starting on naltrexone. This
is probably related, in part, to the absence of a psychoactive effect
with naltrexone. In certain populations of motivated patients (e.g.,
patients on federal probation), however, naltrexone can be useful
and effective (1374, 1375).
The adverse effects of naltrexone may include dysphoria, anxiety,
and gastrointestinal distress. As previously noted, naltrexone can
precipitate withdrawal in actively opioid-dependent individuals.
Naltrexone's label notes that there is a risk that liver
function test values will increase for some patients, but a review
of the evidence shows that these cases occurred only with higher
daily doses of naltrexone (300 mg/day) or, in rare cases,
in patients who were over age 40 years and on a dose of <300
mg/day (1376). Finally, after discontinuation of chronically
administered naltrexone for the treatment of opioid dependence,
there is an increased sensitivity to opioid effects and an increased
risk that opioid overdose will lead to significant respiratory depression;
this is likely related to the up-regulation of opioid receptors
while a patient is being treated with naltrexone (1377).
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2. Treating intoxication
The care of patients with an opioid use disorder is frequently
complicated by episodes of relapse. Consequently, it is important
in ongoing treatment to recognize and treat intoxication with opioids
or other substances.
Mild to moderate opioid intoxication usually does not require
treatment. An uncomplicated overdose with a short-acting opioid
that has a relatively short half-life, such as heroin, may be treated
in an emergency department, with release after a few hours. Overdose
with longer-acting opioids such as methadone, however, requires
closer inpatient observation for a minimum of 24–48 hours.
In addition, severe opioid overdose, marked by respiratory depression,
may be fatal and requires treatment in an emergency department or
inpatient setting. Naloxone, an opioid antagonist, reverses respiratory
and CNS depression as well as other manifestations of overdose.
(Its use is described in detail in Section II.E.1.) A patient who
deliberately takes an overdose as part of a suicide attempt requires
thorough psychiatric evaluation typically in a hospital setting.
For patients who do not require medical or psychiatric hospitalization,
appropriate follow-up is a necessary part of discharge planning.
An opioid-dependent individual may undergo opioid withdrawal
rather than be maintained in methadone or buprenorphine treatment
if, for example, the patient has a relatively short history of opioid
abuse with a good prognosis for remaining abstinent without pharmacological
maintenance, no maintenance treatment program is available locally,
or the patient desires to not be restricted by the requirements
of maintenance medication. Some patients successfully maintained
on a medication such as methadone or buprenorphine will also want
to undergo medically supervised withdrawal.
Criteria for withdrawing patients from long-term maintenance
on methadone or buprenorphine include demonstrated progress toward
a drug-free lifestyle, stability in personal and occupational adjustment,
the absence of other substance use disorders, and successful treatment
and remission of any co-occurring psychiatric disorders.
Precipitous discharge from maintenance programs and concurrent
withdrawal of methadone are associated with a high rate of relapse
to illicit opioid use, arrests, and death. Voluntary termination
of methadone maintenance also carries a high risk of relapse, even
for patients who have responded well to treatment. Patients who
voluntarily discontinue maintenance treatment should receive supportive
treatment during withdrawal as well as aftercare services to aid
in maintaining abstinence. Patients who relapse repeatedly despite
such support should be given the option of voluntary long-term maintenance
on methadone or buprenorphine.
The goal of opioid tapering is to minimize acute withdrawal
symptoms and help patients transition to long-term treatment for
opioid dependence. The use of standard rating scales for withdrawal
(e.g., Clinical Institute Narcotic Assessment) can help guide dosing
in an objective and routine manner. Five pharmacological strategies
are in general use: 1) methadone substitution, with gradual methadone
tapering; 2) abrupt discontinuation of opioids, with use of clonidine
to suppress withdrawal symptoms; 3) clonidine-naltrexone detoxification,
where withdrawal symptoms are precipitated by naltrexone and then
suppressed by clonidine; 4) buprenorphine substitution, followed
by abrupt or gradual discontinuation of buprenorphine; and 5) use
of other medications to treat the symptoms of opioid withdrawal.
+
a) Use of methadone
for withdrawal
Methadone hydrochloride is highly effective in ameliorating
the symptoms of opioid withdrawal. Although the use of opioids to
detoxify or maintain opioid-dependent patients requires special
licensing (see Section II.H.3), this regulation is waived for inpatients
admitted primarily because of a life-threatening general medical
or psychiatric condition who also require methadone to stabilize
their opioid dependence during the inpatient stay.
Inpatient opioid withdrawal with methadone involves stabilizing
a patient on a daily methadone dose that is determined by the patient's
response based on objective withdrawal signs (1378, 1379). Once
the stabilization dose is determined (usually 40–60 mg/day
and sometimes less), methadone can be tapered, for example, by increments
of 5 mg/day. In inpatient settings, detoxification from
heroin or other short-acting opioids can usually be completed within
7 days, but a more gradual tapering will result in a smoother clinical course.
When compared with inpatient withdrawal, outpatient opioid
withdrawal uses a higher initial dose of methadone and occurs over
a longer period of time. The goal of using a higher initial dose
of methadone is to help dependent individuals end illicit opioid
use. Because studies have suggested that slow tapers are associated
with better outcomes, methadone should be tapered gradually over
a period of weeks. Many patients tolerate methadone reductions to
20–30 mg/day with little difficulty, but further
dose reductions may lead to increasing withdrawal distress. Even
with gradual reductions in the dose, such distress may be difficult
for some patients to tolerate and may be accompanied by high dropout
and relapse rates during this later phase of withdrawal.
+
b) Use of clonidine
for withdrawal
Clonidine is a centrally acting 2-adrenergic
antihypertensive medication that effectively decreases the noradrenergic
hyperactivity associated with opioid withdrawal. Clonidine is not
approved for opioid withdrawal in the United States but has been
extensively studied and used for this indication elsewhere. Clonidine
reduces withdrawal symptoms such as nausea, vomiting, diarrhea, cramps,
and sweating but, unlike methadone, does little to reduce other
symptoms such as muscle aches, insomnia, distress, and drug craving
(1380, 1381). As a nonopioid medication, clonidine has some advantages
over methadone for withdrawal. For example, clonidine does not produce
opioid-like tolerance or dependence or the postmethadone rebound in
withdrawal symptoms (1382). In addition, patients completing a course
of clonidine-assisted withdrawal can immediately be given an opioid
antagonist (e.g., naltrexone) if indicated. The disadvantages of
clonidine include its aforementioned inability to improve certain
opioid withdrawal symptoms, associated hypotension that can be profound
despite the use of low doses of this medication, and its possible
sedative effects. Contraindications to the use of clonidine include
acute or chronic cardiac disorders, renal or metabolic disease,
and moderate to severe hypotension (1383).
On the first day of clonidine-aided detoxification, a clonidine
dose of 0.1 mg three times daily (totaling 0.3 mg per 24 hours)
is usually sufficient to suppress signs of opioid withdrawal; inpatients
can generally receive higher doses to block withdrawal symptoms
because of the availability of medical staff to monitor the patient
for hypotension and sedation. The dose is adjusted until withdrawal
symptoms are reduced. If the patient's blood pressure falls
below 90/60 mm Hg, the next dose should be withheld, after
which tapering can be resumed while the patient is monitored for
signs of withdrawal. In the case of short-acting opioids such as
heroin, clonidine-aided withdrawal usually takes 4–6 days. Other
medications may be used along with clonidine to treat withdrawal
symptoms.
In general, clonidine-assisted detoxification is easier to
carry out and monitor in inpatient settings. Clonidine-induced sedation
is also less of a problem for inpatients. However, when delivered
by experienced staff, outpatient detoxification with clonidine is
a reasonable approach (1384–1386). Outpatients should not
be given more than a 3-day supply of clonidine for unsupervised
use because treatment requires careful dose titration and clonidine
overdoses can be life-threatening (1387, 1388).
Clonidine can be an effective alternative to methadone for
treating opiate withdrawal; the completion rate for clonidine-treated
outpatients is relatively low and roughly comparable to that of
methadone withdrawal (1387, 1389).
+
c) Use of clonidine-naltrexone
for rapid withdrawal
The combined use of clonidine and naltrexone for rapidly withdrawing
patients from an opioid has been demonstrated to be safe and effective.
Essentially, naltrexone-precipitated withdrawal is avoided by pretreating
the patient with clonidine. This technique is most useful for opioid-dependent
patients who are in transition to narcotic antagonist treatment.
The limitations of this method include the need to monitor patients
for 8 hours on the first day because of the potential severity of
naltrexone-induced withdrawal and the need for careful blood pressure
monitoring during the entire detoxification procedure. However,
relapse rates with naltrexone maintenance are high.
A related technique is to withdraw a patient from an opioid
while the patient is maintained under general anesthesia. This technique
has been called ultra-rapid opioid detoxification and has included
naltrexone maintenance after the acute withdrawal is completed. Although
some small uncontrolled studies have reported good long-term outcomes
with this method, it appears to be no more effective than methadone
detoxification in achieving beneficial outcomes such as maintenance
of abstinence (1390). In addition, complications associated with
such rapid withdrawal procedures (e.g., general anesthesia) coupled
with the lack of better long-term results suggest that the procedure
should not be commonly used (1390).
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d) Use of buprenorphine
for withdrawal
Prior to buprenorphine's approval in the United States
for the treatment of opioid dependence, there were reports of the
efficacy and safety of its analgesic form when used for medically
supervised opioid withdrawal. Clinicians used parenteral buprenorphine
for relatively short opioid withdrawal (1 week), administered
by injection or provided in the liquid (analgesic) form sublingually.
Now with FDA approval of the sublingual form of this medication,
the analgesic form for opioid withdrawal should no longer be used,
and this nonapproved use of injectable buprenorphine is not recommended.
Studies of buprenorphine for opioid withdrawal have generally
found that it has greater patient acceptability and is more effective
than clonidine (1384, 1391–1393), with the two medications
differing on measures of subjective symptoms of opioid withdrawal.
Well-designed and executed studies comparing buprenorphine to methadone
for the treatment of opioid withdrawal have not been published.
When buprenorphine is used for inpatient opioid withdrawal,
patients can be stabilized on a relatively low dose of daily sublingual
buprenorphine (e.g., 8 mg/day), with the goal of suppressing
opioid withdrawal symptoms. Both tablet forms (with or without naloxone) can
be used in an inpatient setting, as the risk of diversion and parenteral
abuse is low. The dose can be decreased in increments of 2 mg/day
over several days. Because buprenorphine has a long duration of
action, minimal withdrawal symptoms are seen during the dose reduction.
However, some clinicians report that withdrawal symptoms can appear
several days after the last dose of buprenorphine, after a patient
is discharged from an inpatient setting.
If buprenorphine is used for the outpatient treatment of opioid
withdrawal, then procedures similar to those described earlier for
methadone should be followed. But the tablet form combined with
naloxone is preferred. For example, patients should be initially
stabilized on a daily dose (probably 8–32 mg/day)
of buprenorphine that suppresses opioid withdrawal and results in
abstinence from illicit opioid use. Dose reductions should then
occur gradually over a period of 10–14 days. Because buprenorphine
tablets are not scored, the smallest dose increment reduction possible
is 2 mg.
It should be emphasized that concurrent nonpharmacological
treatments should be used to maximize the likelihood of maintaining
abstinence throughout and after withdrawal. However, long-term outcomes
associated with withdrawal are generally poorer than those seen
with maintenance treatments (1394).
+
e) Use of other medications
Some clinicians and treatment programs have used medications
targeting the symptoms of opioid withdrawal as the primary means
for treating this condition. For example, sedative-hypnotics or
anxiolytics are used to treat insomnia and/or anxiety,
antiemetics are prescribed to treat nausea and vomiting, NSAIDs
are provided for muscle cramps, and antispasmodics are used to treat
gastrointestinal cramping. There are limited controlled data about
the use of such medications for the treatment of opioid withdrawal.
Some psychiatrists maintain that the abuse potential of sedative-hypnotics
and anxiolytics is too great to be used with these patients and
that these medications may also precipitate craving for opioids
and relapse. Others feel that for carefully selected patients and
with appropriate monitoring, the use of benzodiazepines over a relatively
brief period (i.e., 1–2 weeks) may be helpful in ameliorating
the often debilitating insomnia that can accompany opioid withdrawal
(1395). Diphenhydramine, hydroxyzine, and sedating antidepressants
(e.g., doxepin, amitriptyline, trazodone) have also been used for
this purpose. It should be noted that these medications have also
been abused, although much less often than benzodiazepines (129).
Other medications such as NSAIDs and antispasmodics may be safely
provided but appear to be less effective than mu agonist opioids
for symptom relief.
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D. Psychosocial Treatments
When considering psychosocial treatments for treating opioid-related
disorders, it is essential to note that all clinical trials of psychosocial
interventions for opioid abusers have taken place in programs that
also provide either opioid agonist maintenance (e.g., methadone)
or treatment with opioid antagonists. Although some follow-up studies
of naturalistic treatment have found equivalent efficacy for methadone
maintenance and outpatient drug-free programs for heroin users (61, 1396–1398), early attempts at providing psychotherapy alone
yielded unacceptably high attrition rates (1399).
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1. Cognitive-behavioral
therapies
In individuals who are receiving methadone maintenance, CBT
is efficacious in reducing illicit substance use and achieving a
wide range of other treatment goals. The benefits of CBT in combination
with drug counseling are equivalent to those of drug counseling alone
or drug counseling plus supportive-expressive psychotherapy in patients
with low levels of psychiatric symptoms; however, in the presence
of higher degrees of depression or other psychiatric symptoms, supportive-expressive
therapy or CBT has been shown to be much more effective than drug
counseling alone (177, 218, 531, 1400, 1401). CBT may also help
reduce other target symptoms or behaviors (e.g., HIV risk behaviors)
in opioid-using individuals (1402). Group-based relapse prevention
therapy, when combined with self-help group participation, may also
help recently detoxified patients reduce opioid use and criminal
activities and decrease unemployment rates (1403).
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2. Behavioral therapies
Contingency management approaches are beneficial in reducing
the use of illicit substances in opioid-dependent individuals who
are maintained on methadone (170, 195, 1295). Although other reinforcers
or rewards (e.g., vouchers for movie tickets or sporting goods)
may be provided to patients who demonstrate specified target behaviors
(e.g., providing drug-free urine specimens, accomplishing specific
treatment goals, attending treatment sessions), methadone take-home
privileges are a commonly offered and effective incentive that is
made contingent on reduced drug use (197–199, 202). Furthermore,
contingency management, either alone or in conjunction with family
therapies, can also be used to enhance adherence with unpopular
treatments such as naltrexone and has been shown to result in diminutions
in drug use among recently detoxified opioid-dependent individuals
(165–167, 1404–1407).
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3. Psychodynamic
and interpersonal therapies
The utility of adding a psychodynamic therapy to a program
of methadone maintenance has been investigated. The provision of
supportive-expressive therapy, a specific approach to such treatment,
may be particularly helpful for patients with high levels of other
psychiatric symptoms (177, 218) (see Section VII.D.1). However,
in terms of individual IPT, the potential benefits of treatment
are unclear, as it is very difficult to engage opioid-dependent patients
in such approaches. Psychodynamically oriented group therapy, modified
for substance-dependent patients, appears to be effective in promoting
abstinence when combined with behavioral monitoring and individual
supportive psychotherapy (1301).
Family therapy has been demonstrated to enhance treatment
adherence and facilitate implementation and monitoring of contingency
contracts with opioid-dependent patients (1408, 1409). Family therapies
are described in detail in Section II.F.8.
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5. Self-help groups
and 12-step-oriented treatments
Self-help groups, such as Narcotics Anonymous, are beneficial
for some individuals in providing peer support for continued participation
in treatment, avoiding substance-using peers and high-risk environments,
confronting denial, and intervening early in patterns of thinking
and behavior that often lead to relapse. Because of the emphasis
on abstinence in the 12-step treatment philosophy, patients maintained
on methadone or other opioid agonists may encounter disapproval
for this type of pharmacotherapy at Narcotics Anonymous meetings.
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E. Clinical Features
Influencing Treatment
The treatment implications of various clinical features are
summarized in Section II.G. In addition to these considerations,
specific sequelae and patterns of co-occurring disorders need to
be considered for patients with an opioid use disorder.
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1. Use of multiple
substances
Dependence on alcohol, cocaine, or other substances of abuse
is a frequent problem for opioid-dependent patients. In one study,
cocaine abuse was found to occur in about 60% of patients
entering methadone programs (169). In studies of opioid-dependent
patients in active treatment, rates of cocaine use as high as 40% or
more have been reported (1410–1413). Similarly, heavy drinking
is a problem for an estimated 15%–30% of
methadone-maintained patients, and benzodiazepine abuse may be just
as common in this population (1414, 1415). Comparable data regarding
rates of co-occurring substance use disorders in patients treated
in naltrexone programs are not generally available.
Other co-occurring substance use disorders require special
attention because treatment directed at opioid dependence alone
is unlikely to lead to the cessation of other substance use. Treatment
is generally similar to that described for individual substances
elsewhere in this practice guideline. Increased frequency of behavioral
monitoring (e.g., daily breath or semiweekly urine toxicology testing),
intensified counseling, contingency contracting, referral to specific
self-help groups (e.g., AA), and specialized pharmacological treatments (e.g.,
disulfiram) have all been used with varying degrees of success.
The results of two studies suggest that higher methadone doses coupled
with intensive outpatient treatment may decrease cocaine use by
methadone-maintained patients (1416).
Opioid-dependent patients who are also dependent on other
substances, particularly CNS depressants, should be stabilized with
methadone and then gradually withdrawn from the other substances.
Efforts to abruptly eliminate all substances of abuse will not be
successful with all patients. In such cases, the elimination of
the drugs one at a time may be warranted.
The use of aversive contingencies, such as methadone dose
reduction or even withdrawal, for continued abuse of cocaine (or
sedatives or alcohol) for patients in methadone maintenance treatment
is controversial. Some psychiatrists believe that requiring methadone withdrawal
for persistent substance abuse causes many patients to cease or
greatly limit use, whereas failure to enforce such limits implicitly
gives patients license to continue use. Others believe that methadone
withdrawal is never justified for patients abusing alcohol or other
substances because of the proven efficacy of methadone in reducing
intravenous heroin use, improving social and occupational functioning,
and providing the opportunity to continue to motivate patients to
reduce other substance use.
The reduction of opioid use in patients with a preexisting
co-occurring psychiatric disorder may precipitate the reemergence
of previously controlled psychiatric symptoms (e.g., depression,
mania, psychosis), which in turn may increase the risk of relapse
to substance use (1417).
In prescribing medications for co-occurring non-substance-related
psychiatric disorders, psychiatrists should be alert to the dangers
of medications with a high abuse potential and to possible drug-drug
interactions between opioids and other psychoactive substances (e.g.,
benzodiazepines) (442, 1378, 1400). For example, the use of MAOIs
should be avoided because of their potential interaction with alcohol,
cocaine and other stimulants, and opioids, including meperidine
and dextromethorphan. In general, benzodiazepines with a rapid onset,
such as diazepam and alprazolam, should also be avoided because
of their abuse potential (1418). However, benzodiazepines with a
slow onset and substantially lower abuse potential (e.g., oxazepam,
clorazepate) can probably be used safely for selected patients to, for
example, ameliorate insomnia (Section VII.C.3.e), provided that
appropriate controls are applied (1419). With all other psychotropic
medications, decisions about prescriptions should consider that
patients may not take medications as prescribed; random blood or urine
monitoring can sometimes help in determining adherence.
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3. Comorbid general
medical disorders
The injection of opioids may result in the sclerosing of veins,
cellulitis, abscesses, or, more rarely, tetanus infection. Other
life-threatening infections associated with opioid use by injection
include bacterial endocarditis, hepatitis, and HIV infection. HIV
infection rates have been reported to be as high as 60% among
individuals dependent on heroin in some areas of the United States
(see DSM-IV-TR, p. 275). Counseling on how to reduce HIV risk should
be a routine part of treatment for intravenous opioid users (559).
Tuberculosis is a particularly serious problem among individuals
who inject drugs, especially those dependent on heroin. Infection
with the tubercle bacillus occurs in approximately 10% of
these individuals. For non-HIV-infected patients who test positive
for the purified protein derivative of tuberculin, the lifetime
risk of developing active tuberculosis is approximately 10% and
the 1-year risk is 7%–10% (1420). Guidelines
regarding prophylactic treatment for patients with a positive skin
test have been published (1421).
As described in DSM-IV-TR (p. 275), in addition to the presence
of life-threatening infections, opioid dependence is associated
with a death rate as high as 1.5%–2% per
year from overdose, accidents, injuries, or other general medical
complications.
In addition to the general effects of substance use during
pregnancy (Section II.G.4), opioid use disorders may have adverse
effects on the health of the pregnant woman, the course of the pregnancy,
fetal and early child development, and parenting behavior. In pregnant women
these effects include 1) poor nourishment, with accompanying vitamin
deficiencies or iron- and folic acid-deficiency anemias; 2) general
medical complications from frequent use of contaminated needles
(abscesses, ulcers, thrombophlebitis, bacterial endocarditis, hepatitis,
urinary tract infections, and HIV infection); 3) sexually transmitted
diseases (gonorrhea, chlamydia, syphilis, herpes); and 4) hypertension.
Possible effects of opioid use and the related lifestyle on
the course of the pregnancy include preeclampsia (toxemia), miscarriage,
premature rupture of membranes, and infections. Possible short-
and long-term effects on the infant include low birth weight, prematurity,
stillbirth, neonatal abstinence syndrome, and sudden infant death
syndrome (1327, 1422, 1423). Approximately 50% of the infants
born to women with opioid dependence are physiologically dependent
on opioids and may experience a moderate to severe withdrawal syndrome
requiring pharmacological intervention. However, when socioeconomic
factors (e.g., family disruption, poverty) are controlled for, mild
to moderate neonatal withdrawal does not appear to affect psychomotor
or intellectual development (1423).
The goals of treatment for the pregnant opioid-using patient
include ensuring physiological stabilization and avoidance of opioid
withdrawal; preventing further substance abuse; improving maternal
nutrition; encouraging participation in prenatal care and rehabilitation; reducing
the risk of obstetrical complications, including low birth weight
and neonatal withdrawal, which can be lethal if untreated; and arranging
for appropriate postnatal care when necessary.
Pregnant patients who lack the motivation or psychosocial
support to remain substance free should be considered for methadone
maintenance regardless of their treatment history, as methadone
maintenance improves infant outcomes relative to continued maternal
heroin use (1424–1426). In a randomized comparison of enhanced
and standard methadone maintenance for pregnant opioid-dependent
women, Carroll et al. (1427) found that enhanced treatmentconsisting
of standard treatment (daily methadone medication, weekly group counseling,
and thrice-weekly urine screening) plus weekly prenatal care by
a nurse-midwife, weekly relapse prevention groups, positive contingency
rewards for abstinence, and the provision of therapeutic child care
during treatment visitsresulted in improved neonatal outcomes
(longer gestations and higher birth weights) but did not affect
maternal substance use. Contingency management approaches may also
be implemented to enhance adherence (1299, 1428, 1429). Withdrawal
from methadone is not recommended, except in cases where methadone
treatment is logistically not possible. In cases where medical withdrawal
is necessary, there are no data to suggest that withdrawal is worse
during any one trimester.
Although the long history of methadone use in pregnant women
makes this medication the preferred pharmacotherapeutic agent, a
growing body of evidence suggests that buprenorphine may also be
used. Jones et al. (1430), in a randomized, double-blind, double-dummy,
flexible-dosing, parallel-group controlled trial, compared 4–24
mg/day sublingual buprenorphine to 20–100 mg/day
oral methadone, with treatment starting in the second trimester
of pregnancy. Although the study was limited by its small sample
size, buprenorphine and methadone showed comparable outcomes in
terms of neonatal abstinence syndrome. Data from uncontrolled observations
in more than 300 neonates also suggest that buprenorphine may be
useful in pregnant women, with rates of neonatal abstinence syndrome
possibly less than those observed with methadone treatment during
pregnancy (1431).
Data on other treatments for opioid withdrawal or dependence
during pregnancy are sparse. In particular, data on the safety of
clonidine in pregnant patients are not available. However, a narcotic
antagonist should never be given to a pregnant substance-using patient because
of the risk of spontaneous abortion, premature labor, or stillbirth.