Levetiracetam in Generalized Social Anxiety Disorder: A Double-Blind, Randomized Controlled Trial

Objective: This multicenter, double-blind, placebo-controlled, 2-arm, parallel-group study was carried out to determine the effectiveness and safety of the novel anticonvulsant levetiracetam for the treatment of generalized social anxiety disorder (GSAD).

Method: After a 1-week, single-blind, placebo run-in period, 217 adult outpatients meeting DSM-IV criteria for social anxiety disorder, generalized type, were randomly assigned (1:1) to 12 weeks of double-blind treatment with either levetiracetam (n‘ ‰=‘ ‰111) or placebo (n‘ ‰=‘ ‰106). Participants were required to have scores of ≥‘ ‰60 on the Liebowitz Social Anxiety Scale (LSAS) and a total score of ≤‘ ‰17 on the 17-item Hamilton Depression Rating Scale (HDRS). The primary outcome measure was mean change from baseline on LSAS total score. Levetiracetam was initiated at 250 mg/d and flexibly titrated up to a maximum dose of 3,000 mg/d (1,500 mg bid). Dosage was held stable for the last 6 weeks of treatment. The study was conducted from September 2003 to June 2004.

Results: No statistically significant difference was found between the adjusted mean changes in LSAS score for levetiracetam (−24.4) and placebo (−28.7) using an efficacy intent-to-treat, last- observation-carried-forward analysis. Rates of response (≥‘ ‰30% reduction in LSAS score) were similar with 41.3% (levetiracetam) and 46.6% (placebo). No significant between-group differences were found on secondary outcome measures, which included changes in Sheehan Disability Scale, Clinical Global Impression of Change, and HDRS scores.

Conclusions: Although well-tolerated, levetiracetam failed to separate from placebo in this trial for the treatment of moderate to severe GSAD.

Submitted: December 12, 2008; accepted February 2, 2009.

Online ahead of print: December 15, 2009.

Corresponding author: Murray B. Stein, MD, MPH, Anxiety and Traumatic Stress Disorders Research Program, University of California San Diego, 8939 Villa La Jolla Drive, Suite 200, La Jolla, CA 92037 ([email protected]).