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

Aybala Saricicek, MD; Kathleen Maloney, BA; Boris Lorberg, MD; Anjana Muralidharan, BA; Barbara Ruf, BA; Hilary Blumberg, MD; Gerard Sanacora, MD, PhD; Brian Pittman, MS; Jian Hu, MD; and Zubin Bhagwagar, MD, PhD, MRCPsych
Department of Psychiatry, Yale University, New Haven, Connecticut

This poster presentation was supported by Stanley Medical Research Institute.

Background: The main burden of illness in bipolar disorder is in the depressive pole.¹ There are very few effective, well-validated treatments for bipolar depression. Levetiracetam is a novel anticonvulsant agent showing clear evidence of possibly unique activity in the hippocampus and the amygdala which have been widely implicated in bipolar disorder.² This study investigated the efficacy of levetiracetam add-on therapy compared with placebo in subjects with bipolar depression who have failed to respond conventional treatments.

Methods: This double blind trial randomly assigned 42 outpatients with bipolar disorder who were experiencing a major depressive episode to adjunctive treatment with either placebo or add-on levetiracetam (up to 2000 mg/day) for six weeks with flexible dosing. 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 (MADRS), Clinical Global Impression Scale for use in bipolar illness (CGI-BP), and the Young Mania Rating Scale (YMRS).

Results: Of 42 randomized subjects, 32 received at least one dose of treatment and thus were available for analysis. The mean (SD) levetiracetam daily dose at endpoint evaluation was 1132(425) mg/day. There was no significant difference in change in HDRS score in the levetiracetam group compared to placebo group. There were no differences in secondary outcome variables.

Conclusions: Levetiracetam adjunctive therapy was not superior to placebo in the management of bipolar depression in this small sample group.

References

1. Judd LL, Akiskal HS. Depressive episodes and symptoms dominate the longitudinal course of bipolar disorder. Curr Psychiatry Rep. 2003;5(6):417–418.
2. Muralidharan A, Bhagwagar Z. Potential of levetiracetam in mood disorders: a preliminary review. CNS Drugs. 2006;20(12):969–979.

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