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


OBJECTIVE
To evaluate the efficacy and tolerability of zonisamide when used as an add-on treatment for patients with drug -resistant partial epilepsy.


METHODS
We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register (Cochrane Library Issue 4, 1999). In addition, we contacted Dianippon and Elan Pharma (makers and licensees of zonisamide) and experts in the field to seek any ongoing studies or unpublished studies.


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


METHODS
Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) adverse events. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome.


RESULTS
Three trials were included with 499 patients randomized.


RESULTS
Overall odds ratio (OR, 95% CI) for 50% reduction in seizure frequency compared to placebo was 2.07 (1.36,3.15) 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 (1.74,4. 25). There was insufficient evidence to support a dose response relationship between dose and responder rate. Tolerability: Treatment withdrawal OR compared to placebo was 1.74 (1.03,2.95). Adverse events: ataxia 3.94 (1.23,12.57), somnolence 2.11 (1.11, 3. 98), agitation 3.52 (1.26,9.68), agitation and irritability 2.43(1. 04,5.66) and anorexia 2.98(1.38,6.42) were significantly associated with zonisamide.


CONCLUSIONS
Zonisamide has efficacy as an add-on treatment in patients 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 conform longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes.
Chadwick
D W
DW
Department of Neurological Science, The Walton Centre for Neurology & Neurosurgery, Lower Lane, Fazakerley, Liverpool, Merseyside, UK, L9 7LJ. bessan-p@wcnn.co.uk
Marson
A G
AG
D000927:Anticonvulsants / Q000627:therapeutic use*; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D017211:Treatment Failure; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide