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Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures
S Taylor1, C Tudur Smith, P R Williamson
1Division of Statistics and Operational Research, Department of Mathematical Sciences, University of Liverpool, Peach Street, Liverpool, Merseyside, UK, L69 7ZL. staylor@liverpool.ac.uk
Background:
Worldwide, phenytoin and phenobarbitone are commonly used antiepileptic drugs. They are more likely to be used in the developing world than the developed world, primarily because they are inexpensive. The aim of this review is to summarise data from existing trials comparing phenytoin and phenobarbitone.
Objectives:
To review the effects of phenobarbitone compared to phenytoin when used as monotherapy in patients with partial onset seizures or generalized tonic-clonic seizures with or without other generalized seizure types.
Search Strategy:
Our search strategy has included: a) MEDLINE 1966 to 1998, b) the controlled trials register of the Cochrane Library, c) hand-searching relevant journals, d) the pharmaceutical industry, e) researchers in the field.
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 phenobarbitone 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, and c) 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 to occur earlier on phenobarbitone than phenytoin.
Main Results:
To date, data have been obtained for four of ten studies meeting the inclusion criteria, amounting to 599 patients, or approximately 65% of the potential data. The main overall results (HR, 95% CI) were: a) time to treatment withdrawal 1.62 (1.22 to 2.14), b) time to 12 month remission 0.93 (0.70 to 1.23), c) time to first seizure 0.84 (0.68 to 1.05). These results indicate a statistically significant clinical advantage for phenytoin in terms of treatment withdrawal and a non-significant advantage in terms of 12 month remission. Results for time to first seizure suggest a non-significant clinical advantage for phenobarbitone.
Reviewer'S Conclusions:
The results of this review favour phenytoin over phenobarbitone, as phenobarbitone was significantly more likely to be withdrawn than phenytoin. Given that no significant differences for seizure outcomes were found, the higher withdrawal rate with phenobarbitone may be due to side effects.