Substance Abuse and Bipolar Disorder

Marcia L. Verduin, MD; Bryan K. Tolliver, MD, PhD; Kathleen T. Brady, MD, PhD


December 05, 2005

In This Article


Although pharmacotherapy remains the mainstay of treatment for bipolar disorder, psychotherapeutic augmentation of drug treatment has shown promise.[17] Group therapy approaches -- long a standard part of substance abuse treatment -- have been adapted more recently for use in patients with coexisting bipolar disorder and SUDs.[18,19,20] These efforts have employed a psychoeducational approach to relapse prevention by identifying similarities of recovery and relapse processes in both disorders, educating patients on relapse triggers and coping skills, and promoting improved treatment compliance. Using a manual-based group therapy of 12-20 weekly sessions, Weiss and colleagues have reported significantly improved outcomes on the Addiction Severity Index drug composite score, percentage of months abstinent, and consecutive months abstinent.[20] Though preliminary, further implementation and study of this treatment are warranted.

Despite the high prevalence of co-occurring substance use and bipolar disorders, as well as the mutually detrimental effect of each disorder on course and prognosis of the other, there is a distinct lack of rigorous treatment research in this population. In fact, much of the extant treatment literature on bipolar disorder has excluded individuals with SUDs from clinical trials. Given the co-occurrence rate of nearly 60%, the current treatment literature applies to less than half of the bipolar population, leading to questions of relevance to clinical practice. We discuss evidence supporting the use of a number of mood stabilizing agents in individuals with comorbid SUDs and bipolar disorder below.

Antiepileptic agents. A recent double-blind, placebo-controlled trial evaluated the effect of valproate plus treatment as usual (lithium combined with a psychosocial intervention) vs placebo plus treatment as usual in actively drinking bipolar individuals with alcohol dependence. This study found a significantly lower proportion of heavy drinking days, a trend toward fewer drinks per drinking day, and lower gamma-glutamyl transferase levels in the valproate group.[21] While no significant differences were found in mood stabilization, higher valproate serum concentrations were positively correlated with reduced alcohol consumption. Safety and efficacy are also supported by 2 open-label trials of valproate in bipolar substance users, with decreased number of days of substance use and amount of substances used in the valproate group[22] and no clinically significant changes in hematologic parameters or transaminase levels, even in a subset of individuals actively drinking during the study.[23] Additionally, Salloum and colleagues found that adding naltrexone to valproate in an open-label trial led to improved substance use and mood outcomes as compared with valproate monotherapy.[24]

In a small retrospective study, individuals with bipolar disorder who had responded to either lithium or lamotrigine were interviewed to assess factors related to medication response.[25] Over 70% of individuals who responded to lamotrigine had a co-occurring SUD, as compared with only 21% of individuals responsive to lithium. Additionally, a small open-label trial evaluating lamotrigine as either monotherapy or add-on therapy in individuals with bipolar disorder and cocaine dependence found significant improvement in mood outcomes and craving, but no significant effect on drug use.[26]

While not approved by the US Food and Drug Administration (FDA) for the treatment of bipolar disorder, carbamazepine has documented clinical efficacy in this population.[27] Brady and colleagues[28] conducted a double-blind, placebo-controlled trial evaluating carbamazepine for treatment of cocaine dependence in individuals with and without bipolar spectrum disorders and found a differential effect of reduced cocaine use in the affective disordered group. Additionally, a growing body of literature supports the use of antiepileptic agents, notably carbamazepine and valproate, in the treatment of alcohol withdrawal,[29] further suggesting preferential use of these agents in bipolar alcoholics.

Lithium. As discussed above, individuals with bipolar disorder and SUDs are more likely to have mixed episodes and rapid cycling[10,11]; these presentations typically exhibit preferential response to antiepileptic agents as compared with lithium.[30] Thus, bipolar substance abusers may respond better to antiepileptic agents than to lithium. However, in a double-blind, placebo-controlled study, Geller and colleagues[31] demonstrated that lithium was efficacious in stabilizing mood and decreasing substance use in adolescents with comorbid bipolar disorder and SUDs. In contrast, an open-label study assessing lithium in individuals with cocaine abuse and bipolar spectrum disorders demonstrated little efficacy.[32] Additionally, lithium has been associated with poorer medication compliance than valproate in individuals with co-occurring bipolar disorder and SUDs.[33]

Antipsychotic agents. Atypical antipsychotic agents are increasingly being used in the treatment of bipolar disorder. In fact, the majority of these agents have been FDA approved for acute and, in some cases, maintenance treatment of bipolar disorder. While no rigorous clinical trial data exist to support preferential use of these agents in bipolar individuals with comorbid SUDs, there are preliminary findings suggesting the need for further study.

In one open-label trial, individuals were switched from their current antipsychotic to aripiprazole, a unique dopamine-2 receptor partial agonist, resulting in improvement in mood, craving, and alcohol use.[34] Sattar and colleagues[35] published a case series report in which olanzapine reduced substance use and craving and improved mood outcomes in 3 individuals with comorbid substance use and affective illness. In an open-label trial, quetiapine add-on therapy resulted in improvement in psychiatric symptoms and reduction in cocaine craving in bipolar individuals with cocaine dependence.[36] Several individuals in this study also had alcohol use disorders, and treatment with quetiapine was associated with decreased alcohol craving and use.[37] However, several individuals in this study were concurrently participating in psychosocial substance abuse treatment programs. Finally, in a randomized trial evaluating continuation vs discontinuation of typical antipsychotics in individuals with co-occurring psychiatric illness and substance dependence, reductions in craving were associated with discontinuation of typical neuroleptics.[38] Of note, two thirds of the individuals in the discontinuation group received treatment with quetiapine.

Finally, antidepressants are frequently prescribed as add-on therapy in bipolar disorder. Goldberg and Whiteside[39] reported that individuals with bipolar disorder and a history of SUDs had a significantly greater risk of developing antidepressant-induced mania. Therefore, close monitoring and frequent reassessment of the need for continued antidepressant use in individuals with co-occurring bipolar disorder and SUDs are recommended.


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