Comorbidity of Substance Use and Axis I Psychiatric Disorders

Kathleen T. Brady, MD, PhD


Medscape Psychiatry & Mental Health eJournal. 1998;3(4) 

In This Article

Affective Disorders

Symptoms of depression and mood instability are among the most common psychiatric symptoms seen in individuals with substance use disorders. Data from the ECA study indicate that among those with any affective disorder, 32% had a comorbid addictive disorder. Of the individuals with major depression, 16.5% had a comorbid alcohol-use diagnosis and 18% had a comorbid other-drug-use diagnosis; 56.1% of bipolar individuals had a substance use disorder.[1] Bipolar disorder was the Axis I diagnosis most likely to co-occur with a substance use disorder. An odds ratio was calculated, utilizing the NCS data, to determine the relative risk of co-occurrence between affective disorders and addictive disorders. The calculations revealed an odds ratio of 2.3 for co-occurrence of substance use with any affective disorder, and the odds ratios were 2.7 for major depression and 9.2 for bipolar disorder.[3]

Studies in treatment-seeking samples have found similarly high estimates of the comorbidity of affective illness with substance use disorders. Estimates of the prevalence of depressive disorders in treatment-seeking alcoholics ranged from 15% to 67%.[19,20] In studies of cocaine-dependent individuals, estimates of affective comorbidity ranged from 33% to 53%.[21,22,23] In the cocaine-dependent populations, bipolar spectrum disorders appeared to be more prevalent (20%-30%) than in alcoholic populations. In opiate-dependent populations, rates of lifetime affective disorder ranged from 16% to 75% and consisted primarily of depressive disorders.[24,25,26,27] Studies of samples of those seeking treatment for affective disorders indicated that 30% to 50% of patients with depressive disorders had a lifetime substance use disorder and 50% to 70% of individuals with bipolar disorder had a lifetime substance use disorder.[28,29]

Diagnosing an affective disorder in the face of substance abuse can be particularly difficult. Both stimulant use and alcohol intoxication can cause symptoms indistinguishable from mania or hypomania, and withdrawal states often cause symptoms of anxiety and depression. Addictive use of drugs is also associated with lifestyles and behaviors that lead to multiple losses and stressors in one's life. These losses may precipitate a depressed affect that is appropriate and transient.

Studies have indicated that up to 98% of individuals presenting for substance abuse treatment have some symptoms of depression.[30] In 1 study, depressive symptoms were monitored over a 1-month period in 171 individuals presenting for alcohol treatment.[31] At admission, 67% had high depression ratings, but by discharge, the figure had dropped to only 16%. While it is important not to make a diagnosis too early and overtreat depression, it is also important to recognize that the population in substance abuse treatment is at enhanced risk for depression and must be carefully assessed.

It is often easier to diagnose mania in the substance abuser. During active drug use, urine drug screens can be useful for evaluating substance-induced mania, and withdrawal states generally do not mimic mania. Manic symptoms that persist for a number of days after last substance use are not likely to be substance-induced because substance-induced mania generally lasts only for the duration of the drug's pharmacologic effect. Long-acting stimulants (methamphetamine) and hallucinogens may be an exception to this rule, as manic symptoms resulting from intoxication with these substances may last for several days.

Recent studies of tricyclic antidepressants (TCAs) indicate that antidepressant treatment may be helpful in individuals with comorbid alcohol dependence and depression (Table I). In a 12-week placebo-controlled trial of imipramine treatment in actively drinking alcoholic outpatients with depression,[32] imipramine treatment was associated with improvement in depression and a more marked lowering of alcohol consumption. Mason and colleagues[33] found that using desipramine to treat alcoholics who had secondary depression (onset of depression after establishment of alcohol dependence) lessened the depression and lengthened the period of alcohol abstinence.

Research on use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of alcoholism has shown promise. The serotonin system has been implicated in the control of alcohol intake.[14] A number of selective serotonin agents have been shown to have a modest effect in lowering alcohol consumption in problem drinkers and alcoholics.[34] A recently published study of depressed alcoholics treated with fluoxetine showed improvement in depression as well as reduced alcohol consumption while in treatment.[35]

Several trials of tricyclic antidepressants have been performed with opioid-dependent patients. Doxepin has been shown in several studies of methadone-maintained patients to relieve symptoms of depression, anxiety, and drug craving. It must be noted that methadone maintenance clinics have reported abuse of amitriptyline and other sedating TCAs. TCA plasma-level monitoring is important in methadone-maintained patients because patients receiving methadone and desipramine have been found to have elevated plasma desipramine levels thought to be due to methadone/desipramine drug interactions.[36]

The use of tricyclic antidepressants in cocaine-dependent patients has focused primarily on the treatment of cocaine dependence rather than the treatment of depression. Several studies using desipramine have shown improvement in anhedonia and cocaine craving and increased initial abstinence in nondepressed patients,[37] and 1 small study showed improved affect in depressed patients.[38] Clinicians should be aware, however, that desipramine may have an activating effect in cocaine-dependent individuals, which can precipitate relapse to cocaine use. Also, TCAs may have additive cardiotoxicity in combination with cocaine, should a cocaine-abuse relapse occur.[36] Other antidepressants have shown preliminary efficacy in the treatment of cocaine dependence, but none have been explored specifically in depressed cocaine-dependent individuals.

Unfortunately, there are very few published data on the treatment of bipolar disorder that is complicated by substance abuse. Currently, the agents that are generally used for the treatment of bipolar disorder include lithium and the anticonvulsant medications, carbamazepine and valproate. Lithium has been used as the standard treatment of bipolar disorder for several decades. In several studies, however, substance abuse has been listed as a predictor of poor response to lithium.[39,40]

Many individuals with bipolar disorder have mixed manic episodes (concurrent symptoms of mania and depression) and rapid-cycling episodes (>4 episodes per year). Several studies have concluded that patients with mixed and/or rapid-cycling bipolar disorder are more likely to respond to anticonvulsant medications than to lithium (Table I).[41,42] Bipolar patients with concomitant substance use disorders appear to have more mixed and/or rapid cycling episodes and, therefore, may respond better to anticonvulsant medications (eg, valproate) than to lithium therapy. An open-label pilot study[43] found valproate to be safe and effective in 9 mixed manic-bipolar patients with concurrent substance dependence.

When treating acute mania, the other traditional agents (eg, neuroleptics, benzodiazepines) are also useful. When using benzodiazepines on an outpatient basis, it may be prudent to use agents that have a longer onset of action (eg, clonazepam) because these agents appear to have less potential for abuse. It is also advisable to use benzodiazepines in a time-limited symptom-oriented manner and to prescribe only small amounts at any one time.

Psychotherapeutic interventions are useful in the treatment of both affective disorders and substance use disorders and are a critical element in the treatment of patients with comorbidity. Although most experts agree that psychotherapy is an important component of treatment, there is less consensus concerning the most appropriate psychotherapeutic treatment. However, mood stabilization alone will not be an effective treatment for a substance use disorder. Adjunctive therapy and psychosocial rehabilitation are necessary.

A wide range of psychotherapeutic interventions have been used to treat affective disorders. These include psychodynamic, interpersonal, cognitive, behavioral, and family therapy.[44] Judgments concerning the effectiveness of these treatments are primarily based on clinical consensus rather than controlled clinical trials; however, studies of several of these treatments are currently being conducted.

The psychotherapeutic/psychosocial strategies used should be individualized and should contain elements of effective treatment from both the substance abuse and affective disorders areas. Many of the principles of cognitive behavioral therapy are common to the treatment of affective disorder as well as substance use disorders. Alcoholics Anonymous and Narcotics Anonymous are available in all communities, and active participation can be a major factor in an individual's recovery. Emphasis on developing therapies specifically to treat individuals with comorbid affective and substance use disorders by combining techniques traditionally used to treat both disorders separately will be a fruitful area for further work. Meanwhile, substance use disorders should be aggressively addressed in patients with affective disorders.


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