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% 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.


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


METHODS
We searched the Cochrane Epilepsy Group Specialized Register (August 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field to seek any ongoing/unpublished studies.


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


METHODS
Two review authors independently selected trials for inclusion and extracted data. Outcomes were: (1) 50% or greater reduction in total seizure frequency; (2) treatment withdrawal; (3) adverse events. Primary analyses were intention-to-treat. Summary relative risks (RRs) were estimated for each outcome.


RESULTS
Four trials (850 participants) were included. The overall RR with 95% confidence intervals (CIs) for 50% reduction in seizure frequency compared to placebo for 300 to 500 mg/day of zonisamide was 2.44 (95% CI 1.81 to 3.30). The RR for any dose zonisamide (100 to 500 mg per day) was 2.35 (1.74 to 3.17). Two trials provide evidence of a dose response relationship for this outcome. The RR for treatment withdrawal for 300 to 500 mg/day zonisamide compared to placebo was 1.64 (1.20 to 2.26), and for 100 to 500 mg per day was 1.47 (1.07 to 2.02). The CIs of the following adverse effects indicate that they are significantly associated with zonisamide: ataxia 4.50 (99% CI 1.05 to 19.22); dizziness 1.77 (99% CI 1.00 to 3.12); somnolence 1.96 (99% CI 1.12 to 3.44); agitation 2.37 (99% CI 1.00 to 5.64); and anorexia 3.00 (99% CI 1.31 to 6.88).


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.
Chadwick
D W
DW
Department of Neurological Science, Room 2.26 - Clinical Science Centre for Research & Education, Lower Lane, Liverpool, Merseyside, UK L9 7LJ. r.jowett@liv.ac.uk
Marson
A G
AG
D000927:Anticonvulsants / Q000627:therapeutic use*; D004351:Drug Resistance; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D017211:Treatment Failure; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide