Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures.

Purpose: This study was designed to evaluate efficacy and safety of zonisamide (ZNS) as adjunctive treatment for patients with refractory partial seizures.

Methods: This randomized, double-blind, placebo-controlled study was conducted at four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS treatment were given a 7-mg/kg/d dosage. When investigators found that adverse effects could be reduced by gradually introducing ZNS, patients were allowed to begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary efficacy measures were the median percentage reduction from baseline in seizure frequency and the proportion of patients achieving a > or =50% reduction from baseline (responder rate). Patient and physician global assessments also served as indicators of efficacy. Safety was assessed primarily by treatment-emergent adverse events.

Results: ZNS-treated patients had a 28.9% reduction in seizure frequency, which differed significantly from the 4.7% increase in placebo-treated patients. The responder rate for ZNS-treated patients was 26.9%, compared with 16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients and 12.3% of placebo-treated patients considered their condition improved; similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo-treated patients as improved. The most frequently reported adverse events with ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue.

Conclusions: As adjunctive treatment, ZNS was generally well tolerated and significantly improved seizure control among patients with refractory partial seizures.