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A meta-analysis of individual patient responses to lamotrigine or carbamazepine monotherapy

From the Centre for Medical Statistics and Health Evaluation (C.G., P.R.W.), University of Liverpool; and University Division of Neurological Science, Clinical Science Centre for Research and Education (D.W.C., A.G.M.), Liverpool, UK.

Address correspondence and reprint requests to Dr Marson, University Division of Neurological Science, Clinical Science Centre for Research and Education, Lower Lane, Liverpool, L9 7LJ; e-mail: a.g.marson{at}liv.ac.uk

Objective: To compare the effects of carbamazepine and lamotrigine monotherapy for people with partial onset seizures or generalized onset tonic-clonic seizures.

Methods: A systematic review and meta-analysis using data on individual patients from randomized trials comparing lamotrigine with carbamazepine monotherapy. The review draws on the search strategy developed for the Cochrane Epilepsy Group, which searches MEDLINE and the Cochrane Controlled Trials register, and hand searches relevant journals. The outcomes considered were time to antiepileptic drug withdrawal, which would usually be for either inadequate seizure control or unacceptable adverse effects, time to first seizure, and 6-month remission.

Results: Five randomized trials were identified containing data for 1,384 participants. Time to treatment withdrawal significantly improved with lamotrigine compared to carbamazepine (hazard ratio 0.55, 95% CI 0.35 to 0.84, random effects), while time to first seizure (hazard ratio 1.14, 95% CI 0.92 to 1.43, fixed effects) and seizure freedom at 6 months (relative risk 0.92, 95% CI 0.81 to 1.04, fixed effects) favor carbamazepine although the results are not significant.

Conclusions: Lamotrigine is significantly less likely to be withdrawn than carbamazepine, but results for time to first seizure suggest a nonsignificant trend that carbamazepine may be superior in terms of seizure control. Trials were of too short a duration to measure clinically important efficacy outcomes such as time to 12-month remission. Current industry-sponsored trials fail to adequately inform clinical practice and further more clinically relevant trials are needed in which longer-term outcomes are assessed before the place of lamotrigine in the treatment of epilepsy is defined.

Editorial, see page 1294

Disclosure: A.G.M. and D.W.C. have received hospitality and fees for consultancy from GSK; C.G. and P.R.W. report no conflicts of interest.

Received June 2, 2005. Accepted in final form January 19, 2006.

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