Deborah Dauphinais1, Michael Knable1, Joshua Rosenthal1, Mark Polanski1, Norman Rosenthal1. 1. Drs. Dauphinais, MD, Rosenthal, MD, Rosenthal, MD, and Mr. Polanski, BA, Capital Clinical Research Associates 5515 Security Lane, Suite 525, Rockville, MD. Dr. Knable, DO, Bethesda Behavioral Sciences, 4300 Montgomery Avenue, Suite 304A, Bethesda, MD.
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 depression. EXPERIMENTAL DESIGN:One hundred two patients with bipolar disorder, type I or II in the depressed phase 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. MADRS score was the primary outcome variable. Secondary outcome measures included the YMRS, CGI-S, CGI-I, 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 evaluated. Side effects were measured using the SAFTEE. PRINCIPAL OBSERVATIONS: There were no statistically significant differences in response between subjects treated with adjunctive zonisamide vs. placebo controls for the primary or secondary outcome measures. There were also no differences between the groups with regard to response rate or remission rate. CONCLUSIONS: In contrast to preliminary open label studies that suggested a role for zonisamide in bipolar depression, we could not confirm these results in a large double blind controlled study.
RCT Entities:
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 depression. EXPERIMENTAL DESIGN: One hundred two patients with bipolar disorder, type I or II in the depressed phase 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. MADRS score was the primary outcome variable. Secondary outcome measures included the YMRS, CGI-S, CGI-I, 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 evaluated. Side effects were measured using the SAFTEE. PRINCIPAL OBSERVATIONS: There were no statistically significant differences in response between subjects treated with adjunctive zonisamide vs. placebo controls for the primary or secondary outcome measures. There were also no differences between the groups with regard to response rate or remission rate. CONCLUSIONS: In contrast to preliminary open label studies that suggested a role for zonisamide in bipolar depression, we could not confirm these results in a large double blind controlled study.
Authors: Lewis L Judd; Hagop S Akiskal; Pamela J Schettler; William Coryell; Jean Endicott; Jack D Maser; David A Solomon; Andrew C Leon; Martin B Keller Journal: Arch Gen Psychiatry Date: 2003-03
Authors: Susan L McElroy; Mark A Frye; Trisha Suppes; Dawn Dhavale; Paul E Keck; Gabriele S Leverich; Lori Altshuler; Kirk D Denicoff; Willem A Nolen; Ralph Kupka; Heinz Grunze; Jorg Walden; Robert M Post Journal: J Clin Psychiatry Date: 2002-03 Impact factor: 4.384