Double-Blind, Placebo-Controlled Trial of Topiramate (600 mg Daily) for the Treatment of Refractory Partial Epilepsy


Address correspondence and reprint requests to Dr. C. A. Tassinari at Department of Neurological Sciences, University of Bologna, Bellaria Hospital, Via Altura 3, 40139 Bologna, Italy.


Summary: Purpose: We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study.

Methods: Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks.

Results: TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with geqslant R: gt-or-equal, slanted50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity.

Conclusions: The results of the present trial indicate that TPM 600 mgiday is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.