Is adjunctive open-label zonisamide effective for bipolar disorder?
OBJECTIVE
To assess the effectiveness and safety of zonisamide in bipolar disorder.


METHODS
A chart review was conducted of naturalistic treatment with zonisamide in 35 outpatients meeting DSM-IV criteria for bipolar disorder (9 males, 26 females; mean +/- SD age = 29.2 +/- 12.7; 14 with bipolar disorder type I, 6 with bipolar disorder type II, and 14 with bipolar disorder not otherwise specified). Patients received zonisamide adjunctive therapy between January 1994 and December 2004. Treatment response was defined as a Clinical Global Impressions - Improvement (CGI-I) scale score of +2 (much improved) or + 3 (very much improved).


RESULTS
Zonisamide was moderately to markedly effective in 9 subjects (26%). Indication for treatment included depressive (34.3%, [12/35]), manic/hypomanic (28.6%, [10/35]), or mixed (31.4%, [11/35]) symptoms. The mean zonisamide dose was 130 mg/d for a mean duration of treatment of 27.0 +/- 32.3 weeks. Sedation (25%, [4/16]) was the most common side effect; 19/35 (54.3%) reported no side effects. 17/35 (49%) patients terminated early, mostly due to adverse effects (6/35). Using a multivariable model, predictors of response, concurrent mood stabilizers, dose and bipolar subtype (bipolar type I > type II/NOS), were controlled for in this sample.


CONCLUSIONS
In 35 persons with bipolar disorder taking standard mood stabilizers and other psychotropic agents, adjunctive zonisamide appears to have modest benefit in global improvement when added to a pre-existing complex medication regimen in patients with bipolar spectrum disorder. These pilot data support the need for larger studies to test the potential efficacy of zonisamide for treatment in mood disorders.
Ghaemi
S Nassir
SN
Bipolar Disorder Research Program, Department of Psychiatry, Emory University, Atlanta, GA 30322, United States. nghaemi@emory.edu
Shirzadi
Arshia A
AA
Klugman
Jeffry
J
Berv
Douglas A
DA
Pardo
Tamara B
TB
Filkowski
Megan M
MM
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000078305:Zonisamide
D000927:Anticonvulsants; D018692:Antimanic Agents; D007555:Isoxazoles; D000078305:Zonisamide