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J Clin Psychiatry. 1995 Mar;56(3):118-21.

Valproate in the treatment of acute bipolar affective episodes complicated by substance abuse: a pilot study.

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Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.



Bipolar disorder is commonly complicated by comorbid substance dependence. Little is known about treatment of this important subpopulation of patients with bipolar disorder. The following study was designed to preliminary explore the use of valproate in a group of patients with comorbid bipolar disorder and substance dependence.


Nine patients with bipolar disorder, as defined by DSM-III-R, and concurrent substance dependence (five alcohol, three polysubstance abuse, one cocaine) were treated with valproate in an open-label, nonblinded trial. Subjects were followed for a mean of 16 weeks. Ratings included measures of affective state (Young Mania Rating Scale, Hamilton Rating Scale for Depression [HAM-D]) as well as substance use (Time-Line Follow-Back).


Patients tolerated valproate well with minimal reports of side effects and no liver toxicity or increase in liver function tests noted. The mean +/- SD maintenance dose of valproate was 1583 +/- 204 mg/day. Subjects evidenced significant decreases in both depression (HAM-D score 17.8 vs. 10.4, p < or = .005) and mania (Young Mania Rating Scale score 12.0 vs. 4.9, p < or = .001) ratings by Week 4, which were sustained throughout the study period. There was a significant decrease in number of days of substance use (t = 4.7, p < or = .005) as well as the amount of substances used during the follow-up period as compared with the month before valproate treatment.


While limited by the open-label, nonblinded nature of the design, this study provides preliminary evidence for the efficacy of valproate in the acute treatment of bipolar episodes complicated by concomitant substance dependence. The medication was well tolerated, and no unacceptable elevations in liver function tests were seen.

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