Zonisamide add-on for drug-resistant partial epilepsy.

BACKGROUND

The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30 per cent develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy.

OBJECTIVES

To evaluate the effects of zonisamide when used as an add-on treatment for people with drug -resistant partial epilepsy.

SEARCH STRATEGY

We searched the Cochrane Epilepsy Group trial register (14/12/01), the Cochrane Controlled Trials Register (Cochrane Library Issue 4, 2001). In addition, we contacted Dainippon and Elan Pharma (makers and licensees of zonisamide) and experts in the field to seek any ongoing studies or unpublished studies.

SELECTION CRITERIA

Randomized placebo controlled add-on trials of zonisamide in people with drug-resistant partial epilepsy.

DATA COLLECTION AND ANALYSIS

Two reviewers independently selected trials for inclusion and extracted relevant data. Outcomes were: (a) fifty per cent or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) adverse events. Primary analyses were intention to treat. Summary odds ratios (ORs) were estimated for each outcome.

MAIN RESULTS

Three trials (499 participants) were included. The overall odds ratio (OR, 95% Confidence Interval (CI)) for 50 per cent reduction in seizure frequency compared to placebo was 2.07(1.36 to 3.15) for a 400mg/day dose of zonisamide. When the full treatment period of 12 weeks was considered for all three trials including varied rates of titration to 400mg/day the OR compared to placebo was 2.72(95% CI 1.74 to 4.25). There was insufficient evidence to support a dose response relationship for this outcome. The OR for treatment withdrawal was 1.74(95% CI 1.03 to 2.95). The 99% CI for the following side effects indicate that they are significantly associated with zonisamide: ataxia 3.94(1.23 to 12.57); somnolence 2.11(1.11 to 3.98); agitation 3.52(1.26 to 9.68); agitation and irritability 2.43(1.04 to 5.66) and anorexia 2.98(1.38 to 6.42).

REVIEWER'S CONCLUSIONS: Zonisamide has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. Minimum effective and maximum tolerated doses cannot be identified. The trials reviewed were of 12 week duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes.