Abstracts

RATIONALE: Zonisamide (Zonegran[reg]) is a broad-spectrum anticonvulsant approved in the United States for the adjunctive treatment of partial seizures in adults with epilepsy. Zonisamide demonstrates multiple mechanisms of action, including blockage of voltage-sensitive sodium channels, reduction of voltage-dependent T-type calcium currents, and reduction of glutamate-mediated synaptic excitation. A number of anticonvulsants are currently used to treat bipolar disorder, suggesting mechanistic similarities between bipolar disorder and epilepsy. Furthermore, a kindling theory of bipolar disorder exists, similar to the kindling model of epilepsy. The objective of the present study was to evaluate the effectiveness of zonisamide as adjunctive treatment in refractory bipolar disorder.
METHODS: This retrospective chart review included 20 outpatients meeting DSM-IV criteria for bipolar spectrum disorder (type I, type II, not otherwise specified, and cyclothymia) who were treated with zonisamide. Clinical response was based on physician-rated Clinical Global Impression scale (CGI) and Global Assessment of Functioning scale (GAF) scores after 4 weeks of zonisamide treatment, as compared with baseline.
RESULTS: Preliminary analysis was performed on 8 zonisamide-treated patients; 6 patients had depression, and 2 patients experienced rapid cycling. Five patients were female and 3 were male with a mean age of 42 [plusminus]5 years. All patients were on other psychotropic medications when zonisamide was added. All 8 patients had previously failed at least 3 adjunctive treatments for bipolar disorder. Mean GAF score significantly improved from baseline (42 [plusminus]3.9) to week 4 (54 [plusminus]4.5, P =.05 from paired t-test). Mean CGI score improved slightly from 4.8 [plusminus]2.5 at baseline to 3.8 [plusminus]3.2 at week 4, but this improvement was not statistically significant. Based on CGI scores of 2 or better, 5 patients (62.5%) were considered responders to zonisamide. Zonisamide was well tolerated with sedation being the most commonly reported adverse event (n=3, 37.5%). No patients discontinued zonisamide due to adverse events.
CONCLUSIONS: These results suggest that zonisamide may be an effective adjunctive treatment in refractory bipolar patients. Zonisamide was also well tolerated in these patients. Though this was a small, open-label study, its results indicate that further research is warranted to investigate the use of zonisamide in bipolar disorder.