Substance-Related Disorders

Dependence is a state comprising cognitive, behavioral, and physiological features that together signify continued substance use despite significant substance-related problems (Table 2). It is a pattern of repeated use lasting at least 12 months that can result in tolerance, withdrawal, and compulsive drug-taking behavior. Not all substances produce tolerance or withdrawal syndromes (see Table 1). Tolerance is the need for greatly increased amounts of a substance to produce a desired effect or a greatly diminished effect with constant use of the same amount of the substance. Withdrawal occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance. In this state the individual will likely take the substance to relieve or to avoid unpleasant withdrawal symptoms. Neither tolerance nor withdrawal is necessary or sufficient for a diagnosis of substance dependence, but a history of tolerance or withdrawal is usually associated with a poorer prognosis.

Substance abuse as defined in DSM-IV-TR includes continued use of a substance, despite significant problems caused by its use, by an individual who does not meet criteria for substance dependence (Table 3). “Failure to fulfill major role obligations” is a criterion. To fulfill an abuse criterion, the substance-related problem must have occurred repeatedly or persistently during the same 12-month period. Substance abuse does not apply to caffeine and nicotine (see Table 1).

Substance intoxication and substance withdrawal are described in Tables 4 and 5, respectively. A diagnosis of a substance-induced mental disorder denotes the presence of a particular syndrome once it has been established that it is the direct result of the substance (via intoxication or withdrawal). Some disorders can persist after the substance has been eliminated from the body, but symptoms lasting more than 4 weeks after acute intoxication or withdrawal are considered manifestations either of a primary mental disorder or of a persisting substance-induced disorder. The differential diagnosis can be complicated: withdrawal from some substances (e.g., sedatives) may look like intoxication with others (e.g., amphetamines).

It is important to distinguish alcohol abuse from dependence; the prognostic implications of the two differ in terms of use, continued meeting of diagnostic criteria, and treatment. The alcohol abuser might not progress to dependence, and the alcohol-dependent person must become abstinent (2). Specifying whether physiological dependence is present has prognostic value, because it indicates a more severe clinical course (3), especially when withdrawal rather than tolerance is the basis for the diagnosis of physiological dependence. The term “primary alcoholism” is used in the context of psychiatric comorbidity. It refers to alcohol dependence that has led to psychopathology, most often an anxiety or mood disorder. “Secondary alcoholism” refers to dependence on alcohol that results from self-medication for an underlying psychiatric disorder. It commonly occurs with schizophrenia and bipolar disorder.

The alcohol-induced disorders include intoxication, withdrawal, intoxication delirium or withdrawal delirium, withdrawal seizures, alcohol-induced persisting dementia, alcohol-induced persisting amnestic disorder (Korsakoff’s syndrome), alcohol-induced psychotic disorder, and sexual dysfunction. Alcohol intoxication is time-limited and reversible, with onset depending on tolerance, amount ingested, and amount absorbed. It is affected by interactions with other substances, medical status, culture, and individual variation.

Delirium tremens can occur during either alcohol withdrawal or alcohol intoxication. Hallucinations may be auditory and of a persecutory nature, or they may be kinesthetic. Delirium tremens can appear suddenly, but usually it occurs gradually 2–3 days after cessation of drinking and reaches its peak intensity on day 4 or 5. It is usually benign and short-lived, subsiding after 3 days in the majority of cases, although subacute symptoms may last weeks. The fatality rate is estimated at less than 1%. Delirium tremens is associated with infections, subdural hematomas, trauma, liver disease, and metabolic disorders. If death occurs during delirium tremens, the cause is usually infectious fat embolism or cardiac arrhythmia (usually associated with hyperkalemia, hyperpyrexia, and poor hydration). Alcohol withdrawal seizures that are not a part of delirium tremens generally occur between 7 and 38 hours after the last alcohol use in chronic drinkers; the average is about 24 hours after the last drink. About 10% of all chronic drinkers experience a grand mal seizure at some time; of these, one-third go on to delirium tremens, and 2% go on to status epilepticus. Alcohol lowers the seizure threshold, which likely contributes to these seizures.

Thiamine deficiency associated with prolonged heavy alcohol use produces alcohol-induced persisting amnestic disorder, or Korsakoff’s syndrome, and its associated neurological deficits—peripheral neuropathy, cerebellar ataxia, and myopathy. Korsakoff’s syndrome often follows acute Wernicke’s encephalopathy—confusion, ataxia, nystagmus, ophthalmoplegia, and other neurological signs. As the encephalopathy subsides, severe impairment of anterograde and retrograde memory remains; confabulation is common. Early treatment of Wernicke’s encephalopathy with large doses of thiamine may prevent the development of Korsakoff’s syndrome.

Opioids refers to all drugs in this class, including heroin, morphine, synthetic drugs, and others. Most individuals with opioid dependence have significant tolerance and experience withdrawal. As noted in Table 1, there are no specific criteria for the diagnosis of opioid dependence or abuse other than the generic criteria. A diagnosis of dependence rather than of abuse is called for when use is accompanied by compulsive behavior related to opioids.

Opioid intoxication and overdose are reversible by the administration of naloxone. Opioid withdrawal is a syndrome that follows a relative reduction in heavy and prolonged use. The syndrome begins within 6–8 hours after the last dose and peaks between 48 and 72 hours; symptoms disappear in 7–10 days. The signs and symptoms are the opposite of those of the acute agonist effects: lacrimation, rhinorrhea, pupillary dilation, piloerection, diaphoresis, diarrhea, yawning, mild hypertension, tachycardia, fever, and insomnia (Table 6). A flulike syndrome subsequently develops, with complaints, demands, and drug seeking. Uncomplicated withdrawal is usually not life-threatening unless a severe underlying disorder, such as cardiac disease, is present. Withdrawal occurs in 60%–94% of neonates of opioid-addicted mothers, beginning 12–24 hours after birth and sometimes persisting for months.

Cocaine use can quickly produce dependence. With cocaine’s short half-life, frequent use is needed to maintain the high. Tolerance occurs with repeated use. The intensity and frequency of cocaine use are less in abuse than in dependence.

Cocaine-induced states must be clearly differentiated from schizophrenia, mood disorders, and anxiety disorders. Cocaine’s autonomic stimulant effects are more common than its depressant effects, which emerge only with chronic high-dose use. In overdose, cocaine’s effects on the noradrenergic system are significant and produce muscular twitching, rhabdomyolysis, seizures, cerebrovascular accident, myocardial infarction, arrhythmia, and respiratory failure. Metabolism is slowed when cocaine is combined with alcohol (producing cocaethylene), which increases the risk of death by 18 to 25 times. Tolerance to cocaine’s euphoric effects can develop during a binge. Often amphetamine or phencyclidine intoxication can be distinguished from cocaine intoxication only through toxicological studies. EEG abnormalities may be present during withdrawal from cocaine. Cocaine intoxication delirium may occur within 24 hours of use. Cocaine intoxication delirium and cocaine-induced psychotic disorder (usually with delusions) are not uncommon and should be kept in mind when evaluating patients with delirium or psychosis.

In amphetamine intoxication, behavioral and psychological changes are accompanied by significant physiological and CNS syndromes. The state begins no more than 1 hour after use, depending on the drug and the method of delivery. “Perceptual disturbances” should be specified when hallucinations or illusions occur in intoxication without delirium if reality testing is intact. If hallucinations or illusions are accompanied by impaired reality testing, the diagnosis of amphetamine-induced psychotic disorder with hallucinations should be considered. Differentiating between amphetamine-induced psychosis and schizophrenia can be difficult (5).

Although the DSM-IV-TR diagnostic criteria for PCP dependence include the first seven items of the generic definition of substance dependence, criteria 2A and 2B may not apply, given that a clear-cut withdrawal pattern is difficult to establish. Adverse reactions to PCP, as with hallucinogens, may be more common among individuals with preexisting mental disorders. PCP dependence may have a rapid onset.

PCP intoxication produces both sympathetic and cholinergic effects. Intoxication begins within 5 minutes of use and peaks within 30 minutes. High-dose intoxication and overdose can produce hyperthermia and involuntary movements followed by amnesia, and coma, analgesia, seizures, and respiratory depression at the highest doses (i.e., greater than 20 mg). Because PCP is lipophilic, intoxication may persist for days. Mydriasis and nystagmus (vertical more than horizontal) are characteristic of PCP use. Perceptual disturbances should be specified if present. Psychosis is the most common PCP-induced mental disorder. Chronic psychosis may occur, along with long-term neuropsychological deficits.

In hallucinogen intoxication, perceptual changes occur alongside full alertness during or shortly after use. Changes include subjective intensification of perceptions, depersonalization, derealization, illusions, hallucinations, and synesthesias. DSM-IV-TR diagnosis requires the presence of at least two of seven physiological signs. Hallucinations are usually visual, often involving geometric forms but sometimes involving persons and objects. Auditory or tactile hallucinations are rare. Reality testing is usually preserved.

Hallucinogen persisting perception disorder (“flashbacks”) after cessation of hallucinogen use involves the reexperiencing of one or more of the same perceptual symptoms experienced while originally intoxicated. These are usually fleeting events, but in rare instances they may be lasting. Symptoms may be triggered by stress, drug use (including that of other drugs), or sensory deprivation, and they may be triggered intentionally. Psychotic disorder not otherwise specified is the proper diagnosis if the patient interprets the perceptions as reality or having origins that are unreal.

The cannabis class includes substances such as marijuana, hashish, and purified delta-9-tetrahydrocannabinol (THC). Usually smoked, these may also be mixed with food and eaten. Intoxication peaks 10–30 minutes after smoking cannabis and lasts about 3 hours. As lipophilic molecules, cannabinoids and their metabolites have a half-life of approximately 50 hours, and their effects may persist for 12–24 hours. At least two of the following signs develop within 2 hours of use: conjunctival injection, increased appetite, dry mouth, and tachycardia. Intoxication with CNS depressants (including alcohol, benzodiazepines, barbiturates, and other drugs), unlike with cannabis, usually decreases appetite, increases aggressive behavior, and produces nystagmus or ataxia. At low doses, hallucinogen intoxication may resemble cannabis intoxication. Acute adverse reactions to cannabis should be differentiated from panic, major depressive disorder, delusional disorder, bipolar disorder, and paranoid schizophrenia.

Cannabis-induced delusional disorder is a syndrome that may occur soon after use. It may be associated with persecutory delusions, marked anxiety, depersonalization, and emotional lability and is often misdiagnosed as schizophrenia. Subsequent amnesia of the episode can occur. Chronic use can cause a syndrome resembling dysthymic disorder.

All of the substances in this class may produce dependence, abuse, or intoxication. There are no specific criteria sets for dependence or abuse of inhalants, partially because of uncertainty about whether tolerance or withdrawal syndromes develop with use of these substances.

Inhalant intoxication involves clinically significant behavioral or psychological changes accompanied by dizziness or visual disturbances, nystagmus, incoordination, slurred speech, unsteady gait, tremor, and euphoria. Higher doses of inhalants may lead to the development of lethargy and psychomotor retardation, generalized muscle weakness, depressed reflexes, stupor, or coma. Inhalant-induced mental disorders may be characterized by symptoms that resemble primary disorders. Mild to moderate intoxication with inhalants can be similar to intoxication caused by CNS depressants.

Prognosis is worsened by the presence of untreated major depression in a patient with primary alcoholism and by the presence of secondary alcoholism in a patient with primary depressive disorder. One study conducted with a large population of alcoholic patients found that primary major depressive episodes were more likely to occur in patients who were female, white, and married, who had experience with fewer drugs and less treatment for alcoholism, who had attempted suicide, and who had a close relative with a major mood disorder (9). Differentiating between primary and secondary alcoholism thus has clinical significance.

The prevalence of major depression ranges from 17% to 30% among persons who are addicted to heroin and is considerably higher among those being treated with methadone. Depressive episodes often are mild, may be related to treatment seeking, and frequently are stress related. In one study, depression was found to be a poor prognostic sign at 2.5-year follow-up in patients addicted to opioids, except in those who had coexistent antisocial personality; for this group, the presence of depression actually improved prognosis (10).

Affective disorders have been concurrently diagnosed in 30% of cocaine addicts, with a significant proportion of these patients having bipolar or cyclothymic disorder. One group has found that alcohol abuse may be more associated with depression, whereas cannabis abuse may be more commonly associated with mania (11).

Psychotic symptoms can result from the use of a wide range of psychoactive substances. Various studies have shown that 50%–60% of schizophrenia patients and 60%–80% of bipolar patients abuse substances (12). Persons with schizophrenia also are more likely than the general population to use tobacco and caffeine. Tobacco use has been associated with lowering of blood levels of neuroleptics. Among patients with cocaine dependence, craving is higher among those with schizophrenia than among those without schizophrenia (13).

The relationship between anxiety and substance use has undergone a great deal of study, and the recent literature has focused particularly on substance use in posttraumatic stress disorder (PTSD). After the disasters of September 11, 2001, an increase was observed in relapse and in new use of substances (14). Alcohol and substance use can increase vulnerability to PTSD, and PTSD can worsen alcohol and drug problems. Pfefferbaum and Doughty (15) found that after the 1995 Oklahoma City bombing, alcohol use among victims increased. Alcohol use was not successful in alleviating symptoms in these individuals, and in fact it increased functional impairment. For a general review of anxiety and alcoholism, see Frances and Borg (16).

Chronic abuse of alcohol, sedatives, or inhalants has been correlated with brain damage and neuropsychological impairment. Such impairment may be obvious (as in alcohol dementia and Korsakoff’s syndrome) or relatively mild and detectable only by neuropsychological testing. Cognitive impairment may be short-lived and recede after 3–4 weeks of abstinence, may improve gradually over several months or years of abstinence, or may be permanent.

Morbidity and mortality due to alcohol are high, especially given the effects of alcohol use on violence and on liver disease (26). About 25% of general hospital admissions are related to chronic alcohol use.

Violence. There is a strong association between alcohol and violence. The suicide rate among persons with alcoholism is 5%–6%. Nearly 50% of violent deaths in the United States, including traffic fatalities, are linked with alcohol (27, 28). In 2001, more than 1 in 10 Americans, or 25.1 million persons, reported having driven under the influence of alcohol at least once in the preceding 12 months (17).

Gastrointestinal effects. Alcoholism is the leading risk factor for cirrhosis, which occurs in 10% of alcoholic persons. Of patients who have chronic pancreatitis, 75% have an alcohol use disorder. Alcoholic hepatitis has a 5-year mortality rate of 50% (29).

Hematological effects. Alcoholism is part of the differential diagnosis for anemia, especially megaloblastic anemia. Alcohol impairs immune function and promotes oropharyngeal, esophageal, gastric, hepatic, breast, and pancreatic cancer.

Endocrinological effects. Alcohol affects male sexual function and fertility directly, through effects on testosterone levels, and indirectly, through testicular atrophy. Increased levels of estrogen in men lead to gynecomastia and body hair loss. In women there may also be severe gonadal failure. Hypoglycemia may result from excessive alcohol ingestion.

Neurological effects. Alcohol increases blood pressure and is associated with an increased risk of cerebrovascular accident. Alcoholic cerebellar degeneration is a slowly evolving condition in patients with a long-standing history of excessive alcohol use. Alcoholic peripheral neuropathy is characterized by stocking-and-glove paresthesia with decreased reflexes and autonomic nerve dysfunction. Other long-term neurological effects of alcoholism include central pontine myelinolysis, Marchiafava-Bignami disease, and muscular pathology.

Cardiovascular effects. Heavy drinkers have an elevated risk of cardiomyopathy and heart failure and lower post–myocardial infarction survival rates. On the other hand, moderate use of alcohol may have beneficial effects on both the risk of heart failure in the elderly (30) and on postinfarction mortality risk (31).

Impurities and contaminated needles may lead to endocarditis, septicemia, pulmonary embolism, pulmonary hypertension, skin infections, hepatitis B, and HIV infection. Because of infection, homicide, suicide, overdose, and AIDS, the death rate of young addicts is 20 times higher than that of nonaddicts.

Violence. Cocaine was found to have been used immediately prior to death in 20% of suicides in New York City in the 1990s (34). Cocaine has also been detected in the urine of homicide victims, in persons arrested for murder, and in persons who have died from overdoses of other drugs.

Psychopathology. Chronic cocaine use depletes all neurotransmitters, leading to increased receptor sensitivity to dopamine and norepinephrine, which is associated with depression, fatigue, poor self-care, low self-esteem, low libido, and mild parkinsonism. Psychosis, an attention-deficit syndrome, and stereotypies may result from continued use. Levels of pathological gambling among cocaine-dependent patients have been found to be five times greater than in the general population (35).

Medical. Whether used intranasally, smoked, or injected, cocaine can lead to a variety of complications, including death, even in recreational, low-dose users. Acute complications include agitation, myocardial infarction, diaphoresis, tachycardia, QRS prolongation, subarachnoid hemorrhage, metabolic and respiratory acidosis, arrhythmia, grand mal seizure, and respiratory arrest. There is evidence of cerebrovascular disease secondary to chronic use (36). Chronic complications of intranasal abuse include nasoseptal defects and dental neglect as a result of cocaine’s anesthetic properties. Intravenous use may produce any of the sequelae of unsterile technique or contaminants.

Urinalysis remains the standard means of testing for alcohol and drugs. Most urinalyses begin with qualitative thin-layer chromatography and immunoassay techniques, including radioimmunoassay or enzyme multiplied immunoassay technique, fluorescence polarization immunoassay, and enzyme-linked immunoassay. More specific and sensitive quantitative testing with combined gas chromatography and mass spectrometry can be performed with certain drugs (e.g., marijuana); this technique constitutes the current gold standard for testing for these drugs, and it may reduce the rate of false positives (70). Advances in analysis of other tissues, including hair, sweat, and saliva, will likely be adopted in laboratory studies in the future.

Assessment of alcohol use is more refined than for other substances, and new developments are expected. Serum levels of cellular enzymes, such as serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), gamma-glutamyltransferase (GGT), and lactate dehydrogenase (LDH) as well as an elevated mean corpuscular volume (MCV) signal recent alcohol abuse. Detection of carbohydrate-deficient transferrin (CDT) will be increasingly important in detecting relapse as well as heavy alcohol use (71). Since the pathogenetic mechanisms of abnormal levels of CDT and SGGT are different, concurrent abnormal results may be a powerful indicator for alcohol use.

Several instruments are available for sensitive measurement of the attributes of alcohol abuse, including the Alcohol Use Inventory (AUI) (72, 73) and the Alcohol Dependence Scale (ADS) (74). Two alcoholism screening tests are the Michigan Alcoholism Screening Test (MAST) and the CAGE questionnaire (75). These tests have the advantage of being self-administered and brief. The short MAST (SMAST) is a 13-item scale that has a correlation of .90 with the 25-item MAST. The proportion of nonalcoholics correctly identified as such averages 74% for the MAST. The TWEAK has been found to be particularly helpful in screening female drinkers (76). The Addiction Severity Index (ASI) (77) has proved to be a useful instrument for use with the substance abuse population, particularly in treatment outcome research. An ASI adapted for teenagers is also available (78).

Individual therapy. Individual therapy can be conducted alone or with other modalities such as pharmacotherapy, 12-step programs, and family and group treatments. The individual modalities include expressive psychotherapy, cognitive behavioral therapy, dialectical behavior therapy, and motivational enhancement therapy. Expressive psychotherapy may lead to deepening of the capacity to tolerate depression and anxiety without substance use (92). Cognitive behavioral therapy is very helpful for relapse prevention as well as for patients who are substance dependent or sociopathic or who suffer from primary psychiatric symptoms (93). Dialectical behavior therapy, a comprehensive, behaviorally oriented treatment designed for highly dysfunctional patients who meet criteria for borderline personality disorder, is being used in the treatment of addiction. This modality has been shown to be more effective than usual treatment for drug abuse in women with borderline personality disorder (94). Motivational enhancement therapy and motivational interviewing were specifically designed for patients with addictive disorders. These are directive, empathic, patient-centered counseling approaches that address the patient’s ambivalence and denial (95, 96).

Group therapy. Treatment programs frequently employ didactic groups, which may help keep patients in treatment, promote cohesiveness, and foster acceptance of long-term rehabilitation. Network therapy involves the creation of a support group—consisting of abstinent family and friends—and then applies cognitive behavioral therapy methods to environmental triggers, uses community reinforcement, and emphasizes the importance of the support of the patient’s social network (97).

Family evaluation and therapy. A family evaluation is warranted for all patients with a substance use disorder; information and aid from the family are crucial for both diagnosis and treatment. Techniques used by family therapists include conjoint family therapy, marital therapy groups, and conjoint hospitalization for married couples. The efficacy of these techniques has been documented (98). In the treatment of addiction in adolescents, family therapy is essential.

Self-help. Every clinician needs to be thoroughly familiar with the work of the 12-step self-help programs: AA, Al-Anon, Narcotics Anonymous (NA), Cocaine Anonymous, Gamblers Anonymous, and Overeaters Anonymous. There is a small but growing body of evidence documenting the efficacy of AA. Self-help also may be very important for cocaine addiction. Peer-led groups have been helpful as well (99).

In the treatment of substance use disorders, medications may be prescribed for detoxification, treatment of comorbid psychiatric disorders or of complicating neuropsychological and medical disorders, aversive treatment, and attenuation of craving or euphoria.

Naltrexone. Naltrexone, an opioid mu-receptor antagonist that is thought to block dopamine release in the nucleus accumbens, was originally indicated for opioid relapse prevention but is now also considered to have superior efficacy for alcohol relapse prevention (100). Because it causes withdrawal from opioid intoxication, naltrexone must be begun slowly over the course of days in the opioid user.

A recent multicenter, double-blind, placebo-controlled evaluation of naltrexone as an adjunct to standardized counseling for alcohol dependence in 627 veterans (almost all men) found no benefit from naltrexone in time to relapse, percentage of days on which drinking occurred, or number of drinks per drinking day (101). The authors concluded that their findings did not support the use of naltrexone for the treatment of chronic alcoholism. Nonetheless, 13 of 15 other studies have found naltrexone to have effectiveness in the treatment of alcohol dependence, which suggests that naltrexone likely is effective for this indication (101).

Methadone and levo-alpha acetyl methadol (LAAM). Methadone, an opioid agonist, has a well-established dose-dependent effect of diminishing the use of opioids and cocaine. Unfortunately, only a minority of opioid-dependent patients receive methadone. LAAM, another opioid agonist, has a longer half-life than methadone and offers the advantage of needing to be taken only three times a week. However, concerns that LAAM may be arrhythmogenic have resulted in a “black box” warning by the Food and Drug Administration. LAAM may not be used as a first-line treatment, and new guidelines for cardiac monitoring have been promoted. In addition, the use LAAM with other medications that inhibit cytochrome P-450 3A4 is contraindicated. Methadone may significantly increase serum levels of zidovudine (102).

Buprenorphine. Buprenorphine is a mixed opioid mu-receptor agonist-antagonist that has been proved superior to placebo for treatment of opioid dependence (103). Buprenorphine shows promise for opioid detoxification and opioid maintenance and for the transition to naltrexone. Suboxone, a 4:1 buprenorphine-naloxone combination in the form of a sublingual tablet, can be used for the same indications as buprenorphine and is not a likely candidate for abuse because if the tablet were crushed and injected, the naloxone would precipitate withdrawal. Buprenorphine is long acting, which means that it can be given three times a week instead of daily (104). At larger doses buprenorphine decreases respiratory drive. Clinicians may obtain formalized training in the use of buprenorphine before prescribing it in the office setting.

Disulfiram. Disulfiram is an aversive treatment for alcohol use. It acts by producing painful symptoms when alcohol is added to a hepatic system exposed to disulfiram and indirectly by blocking the “high” of intoxication unavailable, thus discouraging impulsive alcohol use. Although there is no convincing evidence that use of disulfiram affects long-term outcomes globally, disulfiram has been shown to be useful in certain subtypes of alcoholism, often when it can be administered by a patient’s significant other.

Lithium and mood stabilizers. Lithium and anticonvulsants such as divalproex are an integral component in the treatment of substance use disorders in the presence of an underlying primary bipolar or cyclothymic disorder.

Antidepressants. There is some evidence that sertraline may reduce drinking in alcohol-dependent patients who have no history of depression (105). Bupropion has been used successfully in nicotine cessation, which was recently demonstrated in African American populations (106). Otherwise, antidepressants do not have a direct effect on substance use disorders but are an important adjunct in the treatment of patients with primary mood disorders.

Acamprosate. Acamprosate is a synthetic compound intended to reduce craving for alcohol. It crosses the blood-brain barrier, is chemically similar to amino acid neurotransmitters, and acts at the NMDA receptor to reduce the glutamatergic hyperactivity of dependence. It is dose dependent and has no abuse potential, and giving acamprosate to a patient who is dependent on alcohol will not lead to an acute withdrawal syndrome. This medication may help change the nature of alcohol relapse prevention (107), although Food and Drug Administration approval is uncertain at this time.

In addition to the medications discussed above, a number of other agents may be valuable adjuncts in the treatment of addictive disorders, including nonaddictive anxiolytics such as buspirone and selective serotonin reuptake inhibitors and antipsychotics for the treatment of aggression and psychosis in intoxicated states or delirium, especially alcohol hallucinosis (although they lower the seizure threshold). Among the atypical antipsychotics, olanzapine appears to be as effective as haloperidol in the treatment of cannabis-induced psychotic disorder and has a lower rate of extrapyramidal side effects (108). Opioid detoxification can be accomplished with clonidine, an α₂-adrenergic agonist that has been shown to suppress signs and symptoms of autonomic sympathetic activation during withdrawal, although it has been less successful in decreasing the subjective discomfort of withdrawal (109). Benzodiazepines are the treatment of choice for alcohol or benzodiazepine detoxification. They are generally contraindicated in any substance use disorder except when used for detoxification, for manic patients acutely, or very selectively in compliant abstinent patients with anxiety disorders in whom other treatments have failed.

Rapid and ultrarapid detoxification methods employ opioid antagonists as well as adjuncts such as clonidine, sedatives, and even general anesthesia. However, ultrarapid detoxification has certain drawbacks: it involves the risks associated with anesthesia, it has led to deaths, it is expensive, and it is performed without rehabilitation.

Opioid agonist substitution is the key to maintenance treatment—interrupt the addict’s lifestyle, promote stability and employment, reduce intravenous drug use and the risk it carries of hepatitis B or HIV infection, and reduce criminal activity. Methadone is the standard treatment, and more than 170,000 Americans (only 20%–25% of addicted persons nationwide) are receiving methadone for this purpose. New agents such as buprenorphine (110) are also effective. Naltrexone, when used regularly, can lead to gradual extinction of drug-seeking behavior and can help in opioid relapse prevention. High rates of treatment refusal and treatment dropout limit its use to highly motivated individuals with a good prognosis who are likely to do well with a variety of treatment options and with whom the clinician has a good treatment alliance.

Large-scale studies have suggested that women with substance-related disorders are undertreated (125). In one group of pregnant women with identified psychiatric or substance use disorders, a very poor rate of treatment for substance use (23%) was observed (126).

Until late 2002, epidemiological studies on adolescent substance abuse had found few positive findings. Among the findings from the best available studies from recent years are that 7%–17% of adolescents 13 to 18 years old meet DSM criteria for substance abuse or dependence (137) and that alcohol use (17) and substance use in general (138) are widespread among adolescents. However, preliminary data from 2001 suggest that there may be significant declines in use of some substances in many age groups (17).

Most adolescents in substance treatment programs have comorbid psychopathology, including conduct disorder, depression, attention deficit hyperactivity disorder (ADHD), and others. The Oregon Adolescent Depression Project (139) found that 66.2% of adolescents with a substance use disorder also had a psychiatric disorder but that only 31.3% of those with a psychiatric disorder had a substance use disorder. Substance use disorders are a major risk factor for suicide and suicide attempts among adolescents. The use of methylphenidate in the treatment of ADHD in adolescents has been found to significantly reduce their risk of developing substance abuse in later life (140).

Bipolar disorder in adolescence may be a major risk factor for adult substance use disorders. Biederman et al. found that adolescent-onset bipolar disorder was associated with a greater risk of later having a substance use disorder than child-onset bipolar disorder, regardless of whether conduct disorder was present (141). Geller conducted a double-blind, placebo-controlled, random-assignment, parallel-group, pharmacokinetically dosed study of lithium treatment for adolescents with bipolar disorders and temporally secondary substance dependence disorders (142). Those who received lithium had better outcomes in terms of relapse than those who received placebo, indicating the utility of lithium in bipolar disorder in adolescents and perhaps also in adolescents with primary substance use disorders (143).

Adolescent programs rely heavily on peer support groups, family therapy, organized education, education on drug abuse, 12-step programs such as AA and Alateen, vocational programs, patient-staff meetings, and activity therapy (136). Predictors of treatment completion include greater severity of alcohol abuse, worse abuse of drugs other than alcohol, nicotine, or cannabis; a higher degree of internalizing problems, and lower self-esteem (143).

Interpersonal therapy and cognitive behavioral therapy (144) approaches have been shown to be generally valuable and efficacious for adolescents. Motivational enhancement therapy, originally developed for adults, has been applied to adolescents (145). Contingency management, in which the patient is rewarded for proof of abstinence, is also effective (146). Few investigations of group therapy among adolescent alcohol abusers have been conducted, although this modality’s efficacy has been documented (147, 148). Among the structured group psychotherapies, cognitive behavioral therapy groups have been shown to be superior to interactional groups in reducing use (149). Twelve-step programs geared to younger persons may be of benefit for the few adolescents who have sufficient insight.