Evidence-Based Reviews

Comorbid bipolar disorder and substance abuse: Evidence-based options

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Medication selection may vary based on which substance patients abuse



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Among DSM axis I diagnoses, bipolar disorder (BD) has the highest rates of comorbid substance use disorders (SUDs).1-3 Approximately 60% of patients with bipolar I disorder have a lifetime diagnosis of an SUD.1 Excluding tobacco, alcohol is the substance most often abused by BD patients, followed by cannabis, amphetamines, and cocaine.1-3

BD patients with comorbid SUD usually exhibit more severe clinical presentations and poorer outcomes than their counterparts without SUDs. Compared with patients with BD alone, those with BD and SUD comorbidity (BD-SUD) experience earlier onset of mood symptoms; higher rates of anxiety disorders, suicide attempts, accidents, hospitalizations, and rapid cycling; more depressive episodes; and lower treatment compliance.4-9

Several treatment options are available for patients with BD-SUD, including psychotherapy modalities, medications primarily used to treat BD, and medications primarily used to treat SUDs. Evidence-based support for these treatments remains limited, and no treatment of choice has emerged. This article reviews evidence on the longer-term treatment of BD-SUD, including general strategies and specific psychosocial and pharmacologic interventions. Short-term treatment strategies, such as pharmacotherapy for detoxification, are outside the scope of this review.

General strategies

The causes of BD-SUD are complex. Evidence suggests that the presence of affective symptoms is associated with an increased risk for substance misuse. This should be kept in mind when treating a patient with BD-SUD because controlling mood symptoms probably will help control substance abuse. However, evidence also shows that SUDs may be independent of mood episodes. Therefore, treating only mood symptoms in the hope that doing so will control substance abuse may not be enough.

Because the negative impact of SUDs on BD outcome is well documented, inform patients that limiting their use of alcohol and/or drugs is vital to control their mood disorder. Efforts to educate, stimulate, and support patients to moderate or stop their alcohol and/or drug use are likely to result in positive changes.10 Therefore, treatment for BD-SUD should follow, in part, the same recommendations for treatment of SUDs in patients with no comorbid axis I disorders:

  • identify the problem (ie, the existence of a comorbid SUD)
  • share your concerns with your patient
  • offer appropriate and specific treatments, such as detoxification and/or self-help and counseling programs.10

Because SUDs usually are chronic and relapsing conditions, periods of drug and/ or alcohol use should be expected and not considered a sign of treatment failure. In addition, integrating treatment for both conditions probably is better than managing each separately. Therefore, targeting BD symptoms with mood-stabilizing medications and substance abuse with nonpharmacologic modalities such as drug counseling likely will bring about the best results.

Compared with BD patients without comorbid SUD, BD-SUD patients have a 7-fold increased risk of antidepressantinduced mania.11 Therefore, antidepressants should be prescribed cautiously for patients with BD-SUD.

Integrated psychosocial therapy

BD-SUD patients may benefit from attending self-help programs such as Alcoholics Anonymous and Narcotics Anonymous, provided their mood is stable enough to allow them to participate. Other forms of psychotherapy for BD-SUD patients include standard group drug counseling and integrated group therapy that simultaneously addresses both conditions.

Integrated group therapy is based on the premise that changing maladaptive mood cognitions and behaviors will facilitate recovery from SUDs, and changing maladaptive substance use cognitions and behaviors will facilitate recovery from mood disorders.12 In a recent randomized controlled trial, 62 BD-SUD patients were blindly assigned to integrated group therapy or standard group drug counseling and followed for 3 months.12 Pharmacotherapy was prescribed as usual. Substance use decreased for both groups. However, compared with patients in the drug counseling group, those who participated in integrated group therapy spent fewer days using substances in general and alcohol in particular, fewer days using alcohol to intoxication, and had a shorter time from treatment initiation to the first abstinent month. There were no differences between groups in number of weeks in a mood episode.

Pharmacotherapy options

For a table that summarizes the dosages and indications of the medications used to treat BD-SUD that are described below, visit this article at CurrentPsychiatry.com.


Medications used to treat substance use disorders in bipolar disorder patients*

DrugDosagesFDA-approved indication(s)
Acamprosate1,998 mg/dMaintenance of abstinence from alcohol in patients with alcohol dependence
Aripiprazole15 to 45 mg/dAcute manic or mixed episode of bipolar disorder; augmentation therapy for major depressive disorder
Carbamazepine400 to 1,200 mg/dManic and mixed episodes associated with bipolar disorder
Disulfiram250 to 500 mg/dEnforced sobriety in abstinent alcohol-dependence patients
Divalproex sodiumInitial dose: 750 mg/d
Maximum dose: 60 mg/kg/d
Manic episodes associated with bipolar disorder
Lamotrigine200 mg/dMaintenance treatment of bipolar I disorder
Lithium900 to 1,800 mg/d for acute episodes
900 mg to 1,200 mg/d for maintenance‡.
Manic episodes associated with bipolar disorder; maintenance treatment of bipolar disorder
Naltrexone50 mg/d
380 mg/month
Alcohol dependence
Quetiapine300 mg/d for bipolar depression
400 to 800 mg/d for bipolar mania
400 to 800 mg/d for maintenance treatment of bipolar disorder
Depressive and acute manic episodes associated with bipolar I disorder; maintenance treatment of bipolar I disorder
Risperidone1 to 6 mg/dAcute manic or mixed episodes associated with bipolar I disorder
* None of the medications cited in this table or the text have been specifically approved by the FDA for treating alcohol/drug abuse/dependence co-occurring with bipolar disorder
Dose should correspond to valproic acid therapeutic levels between 50 and 100 μg/mL
Dose should correspond to lithium therapeutic levels between 0.8 and 1.2 mEq/L for acute manic episode treatment and 0.6 and 1.0 mEq/L for maintenance treatment


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