Zonisamide add-on for drug-resistant partial epilepsy

  • Review
  • Intervention

Authors

  • David W Chadwick,

    Corresponding author
    1. Clinical Sciences Centre for Research & Education, University Department of Neurological Science, Liverpool, Merseyside, UK
    • David W Chadwick, University Department of Neurological Science, Clinical Sciences Centre for Research & Education, Lower Lane, Fazakerley, Liverpool, Merseyside, L9 7LJ, UK. r.jowett@liv.ac.uk.

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  • Anthony G Marson

    1. Clinical Sciences Centre for Research & Education, University Department of Neurological Science, Liverpool, Merseyside, UK
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Abstract

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.

Objectives

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

Search methods

We searched the Cochrane Epilepsy Group Specialized Register (July 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2007) and MEDLINE (Ovid, 1950 to July 2007). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field to seek any ongoing/unpublished studies.

Selection criteria

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

Data collection and analysis

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.

Main 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).

Authors' 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.

Plain language summary

Zonisamide add-on for drug-resistant partial epilepsy

Zonisamide in combination with another antiepileptic drug can reduce seizures, but with some adverse effects.

A third of people with epilepsy become resistant to antiepileptic drugs. Older drugs do not prevent seizures for everyone and they have adverse effects. New drugs have been developed as "add-on" treatments to try and improve this. Zonisamide is one of these. The review of trials found that zonisamide significantly reduced seizure frequency for people with drug-resistant partial epilepsy if zonisamide is added to their usual treatment. There is also an increase in adverse effects, and more research is needed.

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