Main Entry Criteria. Neonates, children, and adults with medication-resistant epilepsy on one, two, or three antiepileptic drugs (AEDs)

Comparator. Placebo, zonisamide

Number of Patients. 1,008

Primary Outcome Variable. 50% responder rate

Results. The efficacy of zonisamide in patients with focal-onset epilepsies varied by seizure type. The responder rate was between 50% in patients with complex partial seizures and 60% in patients with secondary generalized seizures. In patients with generalized epilepsies, the responder rate was between 26% in patients with generalized tonic seizures and 62% in patients with absence seizures. The overall best responder rate was noted in patients with idiopathic generalized epilepsies (66%).

Main Entry Criteria. Adults (18 to 59 years) with medication-resistant partial seizures

Comparator. Placebo, zonisamide

Number of Patients. 139

Primary Outcome Variable. Median percentage change in seizure frequency

Results. During treatment with zonisamide, complex partial seizures decreased significantly compared to placebo, as did the median seizure rate. Remission was observed in 6.2%.

Main Entry Criteria. Adolescents and adults (13 to 67 years) with medication-resistant focal-onset seizers

Comparator. Placebo, zonisamide

Number of Patients. 203

Primary Outcome Variable. Median percentage reduction in seizure frequency compared to baseline

Results. Zonisamide at 400 mg/day reduced the median frequency of all seizures by 40.5% from baseline (responder rate 42%) significantly better than placebo.

Main Entry Criteria. Adults with medication-resistant focal-onset epilepsy (17 to 68 years)

Comparator. Placebo, zonisamide (600 mg/day or maximum tolerated dosage)

Number of Patients. 152

Primary Outcome Variable. Median percentage reduction in frequency of all partial seizures relative to baseline and the proportion of patients achieving ≥50% reduction from baseline

Results. Zonisamide-treated patients had a 28.9% reduction in seizure frequency (4.7% increases found in placebo-treated patients). The responder rate for zonisamide-treated patients was 26.9% (16.2% for placebo-treated patients). At the end of the study, 66.2% of zonisamide-treated patients and 12.3% of placebo-treated patients considered their condition improved.

Main Entry Criteria. Adolescents and adults (≥12 years) with medication-resistant partial seizures

Comparator. Placebo; zonisamide 100 mg/day, 300 mg/day, and 500 mg/day

Number of Patients. 351

Primary Outcome Variable. Median percentage change in the frequency of complex partial seizures without secondary generalization and the proportion of responders (defined as ≥50% reduction in the frequency of complex partial seizures)

Results. Compared with placebo, the highest dose of zonisamide (500 mg/day) resulted in a significantly greater decrease in complex partial seizure frequency from baseline (51.2% vs. 16.3%; p<0.0001) and a significantly higher proportion of complex partial seizure responders (52.3% vs. 21.3%; p<0.001). Both zonisamide 500 mg/day and 300 mg/day were statistically superior to placebo in reducing the frequency of “all seizures” and simple partial and complex partial seizures. For all seizures, a significant dose–response relation was observed (p<0.0001).

Main Entry Criteria. Adolescents and adults (12 to 67 years) with medication-resistant partial seizures

Comparator. None

Number of Patients. 167

Primary Outcome Variable. Reduction in the frequency of all seizures with focal onset (simple, complex, and secondary generalized)

Results. The median percentage reduction of partial seizures was 51.8% (from baseline frequency = 11.5 seizures per month to = 5.5 seizures per month). Four persons (3.7%) developed kidney stones and were withdrawn from the study.