Carbamazepine versus phenytoin monotherapy for epilepsy

C Tudur Smith, A G Marson, H E Clough, P R Williamson
Cochrane Database of Systematic Reviews 2002, (2): CD001911

BACKGROUND: Worldwide, carbamazepine and phenytoin are commonly used antiepileptic drugs. This review summarizes evidence from randomized controlled trials in which these two drugs have been compared.

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

SEARCH STRATEGY: We searched: (a) the trial register of the Cochrane Epilepsy Group; (b) The Cochrane Controlled Trials Register (Cochrane Library Issue 4, 2001); (c) MEDLINE 1966-2001. In addition we hand searched relevant journals and contacted the pharmaceutical industry and researchers in the field to seek any ongoing or unpublished studies.

SELECTION CRITERIA: Randomized controlled trials in children or adults with partial onset seizures or generalized onset tonic-clonic seizures. Trials must have included a comparison of carbamazepine monotherapy with phenytoin monotherapy.

DATA COLLECTION AND ANALYSIS: This was an individual patient data review. Outcomes were time to (a) withdrawal of allocated treatment, (b) 12 month remission, (c) six month remission, and (d) first seizure post randomization. Data were analysed using a stratified logrank analysis with results expressed as hazard ratios (HR) and 95% confidence intervals (95% CI), where a HR>1 indicates an event is more likely on phenytoin.

MAIN RESULTS: Individual patient data are available for 551 participants from three trials, representing 63% of the participants recruited into the nine trials that met our inclusion criteria. By convention, for the outcomes time to six and 12 month remission HR>1 indicates a clinical advantage for phenytoin, whilst for time to withdrawal and first seizure HR>1 indicates a clinical advantage for carbamazepine. Results (HR (95% CI)) were: (i) time to withdrawal of allocated treatment 0.97(0.74 to 1.28), (ii) time to 12 month remission 1.00(0.78 to 1.29), (iii) time to six month remission 1.10(0.87 to 1.39), (iv) time to first seizure 0.91(0.74 to 1.12). The results suggest no overall difference between carbamazepine and phenytoin for these outcomes.

REVIEWER'S CONCLUSIONS: We have not found evidence that a significant difference exists between carbamazepine and phenytoin for the outcomes examined in this review. Confidence intervals are wide and the possibility of important differences existing has not been excluded.

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