Levetiracetam in the Management of Bipolar Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective: To study the efficacy of adjunctive levetiracetam therapy compared with placebo in the treatment of subjects with depression with bipolar disorder.

Method: This double-blind, placebo-controlled clinical trial randomly assigned outpatients with bipolar disorder type I and type II who were experiencing a major depressive episode (Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version criteria) to treatment with either placebo or adjunctive levetiracetam (up to 2,500 mg/d flexibly dosed) for 6 weeks. The subjects were recruited from October 2005 to June 2008. The primary efficacy measure was mean change from baseline to week 6 in the Hamilton Depression Rating Scale (21-item). Secondary efficacy assessments included the Montgomery-Åsberg Depression Rating Scale, the Beck Depression Inventory, the Clinical Global Impressions-Bipolar Version scale, the Hamilton Anxiety Rating Scale, and the Young Mania Rating Scale.

Results: Of 42 subjects randomly assigned to placebo or drug, 32 received at least 1 postbaseline assessment and thus were included in the analysis. The mean (SD) levetiracetam daily dose at endpoint evaluation was 1,132 (425) mg/d. There was no significant difference in the mean change from baseline to week 6 in the Hamilton Depression Rating Scale scores for levetiracetam compared with placebo. There were no significant differences in any of the secondary outcome measures.

Conclusions: Levetiracetam adjunctive therapy was not superior to placebo in the short-term treatment of subjects with depression with bipolar disorder in the population studied.

Trial Registration: clinicaltrials.gov Identifier: NCT00566150

J Clin Psychiatry

Submitted: September 1, 2009; accepted November 10, 2009.

Online ahead of print: October 19, 2010 (doi:10.4088/JCP.09m05659gre).

Corresponding author: Zubin Bhagwagar, MD, PhD, MRCPsych, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492 ([email protected]).