Evidence-Based Reviews

Comorbid bipolar disorder and substance abuse: Evidence-based options

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Quetiapine may be effective for treating BD patients with comorbid cocaine dependence. In an open-label study, 12 weeks of quetiapine augmentation in 17 cocaine-dependent BD patients was associated with decreased cocaine craving and improvement in depressive symptoms.22 In another open-label study, 80 BD patients with comorbid cocaine or amphetamine dependence were randomly assigned to receive quetiapine or risperidone as adjunctive therapy or monotherapy for 20 weeks.23 Both groups showed significantly decreased drug use and drug craving and improved mood. This study suggests that risperidone also may be an option for BD patients with comorbid cocaine or stimulant dependence.

A 20-week, open-label study of 20 BD-SUD patients found that switching patients from their previous antipsychotic to aripiprazole resulted in less cocaine craving, less alcohol craving, and less money spent on alcohol.24

Olanzapine has not been systematically studied in BD-SUD patients. Some case reports suggest that olanzapine may decrease cocaine craving and use in patients with schizoaffective disorder (bipolar type) and alcohol craving and use in BD patients with comorbid alcohol dependence.25

Table 3

Evidence of efficacy for antipsychotics for BD patients with SUDs

StudyInterventionDesignSubstance use disorderResults
Martinotti et al,* 200820QuetiapineOpen labelAlcohol dependenceDecreased alcohol consumption and alcohol craving
Brown et al, 200821Quetiapine vs placeboDouble-blind, placebo-controlledAlcohol dependenceNo difference between quetiapine and placebo in decreasing alcohol use and alcohol craving
Brown et al, 200222QuetiapineOpen labelCocaine dependenceDecreased cocaine use and cocaine craving
Nejtek et al, 200823Risperidone vs quetiapineOpen labelCocaine dependence and amphetamine dependenceDecreased drug use and drug craving
Brown et al, 200524AripiprazoleOpen labelAlcohol and cocaine dependenceDecreased alcohol and cocaine craving and money spent on alcohol
*Sample included, but was not limited to, patients with BD
BD: bipolar disorder; SUDs: substance use disorders

SUD medications. Little evidence guides using medications indicated for treating SUDs—such as naltrexone, acamprosate, and disulfiram—as treatment for BD patients (Table 4).26-29 In an open-label trial of 34 BD patients with alcohol dependence, naltrexone was well tolerated and associated with decreased alcohol craving and use and modest improvement in manic and depressive symptoms.26

In a double-blind, placebo-controlled study, 50 alcohol-dependent BD patients treated with standard mood-stabilizing therapy and cognitive-behavioral therapy were randomized to receive add-on naltrexone, 50 mg/d, or placebo.27 Patients receiving naltrexone showed decreased alcohol consumption, although no measures were statistically significant. Effect sizes of alcohol use decrease and alcohol craving were moderate to large compared with placebo, which suggests that naltrexone may be effective for treating alcoholism in these patients.

Two other studies evaluated naltrexone and disulfiram in patients with BD or other mood disorders.28,29 Naltrexone was well tolerated, caused no serious adverse side effects, and was significantly more effective than placebo in decreasing drinking rates and increasing the number of abstinent days.28,29 Disulfiram was as effective as naltrexone, but the combination of both offered no advantage over use of either drug separately.

There are reports of a new-onset manic episode associated with naltrexone use in a patient with opioid dependence, and a manic episode triggered by naltrexone in a patient with BD with comorbid alcohol dependence.30,31 At both low and high doses, disulfiram is associated with induction of psychotic mania in alcoholic patients without a personal or family history of BD.32,33

We found no studies that evaluated treating BD patients who abused other substances, such as cannabis or opiates. We recommend that BD patients with these substance use disorders should be referred to treatment modalities that are condition-specific, such as psychotherapy for cannabis use disorders or methadone or naltrexone treatment for opiate dependence. More severe cases of comorbid SUD probably would benefit from a referral to or consultation with a SUD specialist.

Table 4

Naltrexone and disulfiram for BD patients with alcohol dependence

StudyInterventionDesignSubstance use disorderResults
Brown et al, 200626NaltrexoneOpen labelAlcohol dependenceDecreased alcohol use and craving
Brown et al, 200927Naltrexone vs placeboDouble-blind, placebo-controlledAlcohol dependenceNonsignificant decrease in alcohol consumption
Petrakis et al, 200528 and 200729Naltrexone alone vs disulfiram alone vs naltrexone plus disulfiramDouble-blind, randomized, placebo-controlledAlcohol dependenceMore time in abstinence and decreased craving for both compounds
BD: bipolar disorder

Related Resource

  • Tolliver BK. Bipolar disorder and substance abuse: Overcome the challenges of ‘dual diagnosis’ patients. Current Psychiatry. 2010; 9(8): 32-38.

Drug Brand Names

  • Acamprosate • Campral
  • Aripiprazole • Abilify
  • Carbamazepine • Carbatrol, Equetro, others
  • Disulfiram • Antabuse
  • Divalproex sodium • Depakote,
  • Depakote ER Lamotrigine • Lamictal
  • Lithium • Eskalith, Lithobid
  • Methadone • Dolophine
  • Naltrexone • ReVia, Vivitrol
  • Quetiapine • Seroquel
  • Risperidone • Risperdal
  • Topiramate • Topamax
  • Valproate • Depacon


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