Switching Outpatients With Bipolar or Schizoaffective Disorders and Substance Abuse From Their Current Antipsychotic to Aripiprazole

Objective: Substance abuse is extremely common in patients with bipolar disorders, although minimal data are available on the treatment of this important clinical population. Aripiprazole is an atypical antipsychotic that is approved for the treatment of mania and that has a novel mechanism of action, acting as a dopamine-2 receptor partial agonist, thereby increasing dopamine release in some parts of the brain and decreasing dopamine release in other brain regions. Dopamine release is implicated in substance use, and both dopaminergic agonists and antagonists have been examined for the treatment of substance abuse. To our knowledge, dopamine receptor partial agonists have not been investigated for treatment of substance abuse in humans.

Method: Twenty antipsychotic-treated patients with bipolar or schizoaffective disorder and current substance abuse were switched to open-label aripiprazole using an overlap and taper method. At baseline, diagnoses were confirmed using the Mini-International Neuropsychiatric Interview based on DSM-IV criteria. Psychiatric symptoms, side effects, and substance use and craving were assessed over 12 weeks. Psychiatric symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Substance craving was assessed with visual analogue scales, and side effects were monitored using the Abnormal Involuntary Movement Scale, Simpson- Angus Scale, Barnes Akathisia Scale, and patient report. Study enrollment was from April 2003 to February 2004.

Results: Significant baseline-to-exit improvement in HAM-D (p = .002), YMRS (p = .021), and BPRS (p = .000) scores were observed without a significant change in antipsychotic-induced side effect scales. In 17 participants with current alcohol dependence, significant reductions in dollars spent on alcohol (p = .042) and alcohol craving (p = .003) were found. In 9 participants with cocaine-related disorders, significant reductions in cocaine craving (p = .014), but not use, were found.

Conclusion: A change to aripiprazole was associated with symptomatic improvement. Limitations of the study include a small sample size, high attrition, and an open-label design. Controlled trials in dual-diagnosis patients are needed to confirm these findings.