An open prospective study of zonisamide in acute bipolar depression

Objective: To examine the effectiveness and safety of zonisamide in the treatment of acute bipolar depression. Methods: An open-label, prospective, nonrandomized, 8-week study conducted in bipolar outpatients (type 1, type 11, or not otherwise specified) with depressive symptoms. No patient was manic or mixed at study entry. Previous treatments were continued unchanged, but no new treatments were allowed. Montgomery Asberg Depression Rating Scale and the Mania Rating Scale from the Schedule of Affective Disorders and Schizophrenia-Change Version were used. Results: Twenty patients (10 men, 10 women) with bipolar disorder (17 type I, 2 type II, 1 NOS), aged 38.1 +/- 8.81 years, received zonisamide at mean dose of 222.5 +/- 85.1 mg/d. Mean Montgomery Asberg Depression Rating Scale scores improved significantly from baseline to endpoint (mean difference = -8.4, 95% confidence interval [4.1. 12.6], P = 0.001). Ten patients (50%) terminated early due to adverse effects, mostly side effects including nausea/vomiting, cognitive impairment, and sedation. One patient experienced increased suicidal ideation, and one patient experienced hypomania. Conclusions: This study suggests improvement of depressive symptoms in this sample with 8 weeks of open-label zonisamide treatment.