Lamotrigine versus carbamazepine monotherapy for epilepsy

C L Gamble, P R Williamson, A G Marson
Cochrane Database of Systematic Reviews 2006 January 25, (1): CD001031

BACKGROUND: The choice of an antiepileptic drug (AED) for any individual should take into account reliable information about seizure control, adverse effects and cost. Carbamazepine is the usual drug of choice for people with newly-diagnosed partial onset seizures. Lamotrigine is a relatively new AED which is licensed in many countries for use as an initial monotherapy.

OBJECTIVES: To review the best evidence comparing carbamazepine and lamotrigine when used as monotherapy in people with partial onset seizures, or generalized onset tonic-clonic seizures with or without other generalized seizure types.

SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (TheCochraneLibrary Issue 2, 2005), and MEDLINE (1966 to August 2005). No language restrictions were imposed. We also contacted pharmaceutical companies and trial investigators.

SELECTION CRITERIA: Randomized controlled trials, blinded or unblinded, in which children or adults with partial onset seizures or generalized onset tonic-clonic seizures were randomized to monotherapy with either carbamazepine or lamotrigine.

DATA COLLECTION AND ANALYSIS: This was an individual patient data review. Outcomes were (1) time to treatment withdrawal, (2) time to first seizure post randomization, and (3) seizure freedom at six months. Time to event data were analysed using a stratified logrank analysis with results expressed as hazard ratios (HR) and 95% confidence intervals (95% CI); binary data were expressed as relative risks (RR) and 95% confidence intervals (95% CI). A HR or a RR greater than 1 indicated an event was more likely on lamotrigine than carbamazepine.

MAIN RESULTS: Individual patient data were available for 1384 participants (100% of total randomized) from the five trials that met our inclusion criteria. The main results (HR (95% CI)) were (1) time to treatment withdrawal 0.55 (0.35 to 0.84) (random-effects), (2) time to first seizure post randomization 1.14 (95% CI 0.92 to 1.43), and (3) seizure freedom at six months RR 0.92 (95% CI 0.81 to 1.04). The review suggested that time to treatment withdrawal was significantly improved with lamotrigine compared to carbamazepine, while time to first seizure and seizure freedom at six months favoured carbamazepine although the results were not statistically significant.

AUTHORS' CONCLUSIONS: Lamotrigine was significantly less likely to be withdrawn than carbamazepine but results for time to first seizure suggested that carbamazepine may be superior in terms of seizure control. Trials were of too short a duration to measure important seizure outcomes such as time to 12 month remission. Further trials are needed in which longer-term outcome is assessed as well as measures such as psychosocial outcome and quality of life.

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