Abstract
OBJECTIVE This is the first multicenter, double blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of adjunctive zonisamide for the treatment of bipolar mania or mixed state. EXPERIMENTAL DESIGN One hundred four patients with Bipolar Disorder, Type I, II or NOS, in a manic, hypomanic or mixed state of illness were randomized to either adjunctive zonisamide or placebo. The study consisted of three phases: a 7 to 30 day screening and stabilization phase, 6 weeks of blinded treatment and a 1 to 3 week discontinuation phase. The primary outcome variable for manic and hypomanic patients was the Young Mania Rating Scale (YMRS) both the YMRS and Montgomery Asberg Depression Rating Scale (MADRS) served as primary outcome variables for patients in mixed states. Secondary outcome measures included the Clinical Global Impression for Bipolar Disorder (CGI-BP), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and an a priori analysis of response and remission. Metabolic parameters including weight, waist-hip ratio, body mass index, fasting glucose, cholesterol and triglyceride levels were also analyzed. Side effects were measured using the SAFTEE. PRINCIPAL OBSERVATIONS There were no statistically significant differences for any of the primary or secondary outcome measures between zonisamide and placebo-treated patients. CONCLUSIONS In contrast to previous studies that suggested efficacy of adjunctive zonisamide in bipolar mania or mixed state, these results were not confirmed in this double blind controlled study.
