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.


a) Risk of suicide

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).


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.


c) Sleep disturbances

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.


d) Co-occurring psychiatric and substance use disorders

+ (1) General principles

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.

+ 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.

+ 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).

+ 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.

+ 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).

+ (2) Treatment in the presence of specific co-occurring psychiatric disorders
+ a. Schizophrenia

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).

+ 1) Pharmacotherapy

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).

+ 1) Pharmacotherapy

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 depression—that 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).

+ c. Bipolar disorder

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.

+ d. Anxiety disorders

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).

+ f. Eating disorders

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).

+ 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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