A Preliminary Open-Label Study of Zonisamide Treatment for Bipolar Depression in 10 Patients

Abstract

The purpose of this study was to investigate the effectiveness of zonisamide in the treatment of bipolar depression. Ten patients with DSM-IV bipolar disorder, depressed phase, who had either not tolerated or not responded to previous treatments were given zonisamide in this add-on open-label study. Zonisamide treatment was started at 100 mg/day and increased by 100 mg every 2 weeks to a maximum of 300 mg/day in divided doses (b.i.d. or t.i.d.). Subjects underwent weekly visits at which they were administered the 17-item Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Clinical Global Impressions scale (CGI). Every 2 weeks, subjects also underwent laboratory tests, a urine examination, and a verbal memory test. Outcome measures were analyzed with repeated-measures analysis of variance. Eight subjects completed all 8 weeks of the study. Two subjects completed more than 4 weeks of the study, and their data were analyzed using the last observation carried forward. Bipolar depression subjects had a significant reduction in HAM-D scores (p < .001) and in CGI-Improvement (CGI-I) scores (p < .001). Five of 8 subjects who completed all 8 weeks of the study had more than a 50% decrease in HAM-D scores and were rated much improved on the CGI-I at the end of 8 weeks of treatment. There was no significant drug effect on YMRS scores, weight, or verbal memory. Zonisamide may be a useful drug in the treatment of bipolar depression. Further controlled clinical trials are needed.