Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures

Taylor S, Tudur Smith C, Williamson PR, Marson AG

Published Online:

January 20, 2010

No evidence that phenytoin is better than phenobarbitone at controlling seizures.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Worldwide, phenobarbitone and phenytoin are commonly used antiepileptic drugs. This review found no evidence to suggest a difference between phenobarbitone and phenytoin for the control of the seizure types investigated. Phenobarbitone was more likely to be withdrawn, presumably due to adverse effects.

Abstract (click to read)

Background:

This is an updated version of the original Cochrane review published in Issue 4, 2001.

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 summarize 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:

We searched the Cochrane Epilepsy Group trials register (20 October 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2009) and MEDLINE (1950 to October week 2, 2009). In addition, we handsearched relevant journals, and contacted pharmaceutical companies and researchers in the field to seek any ongoing or unpublished studies.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 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 analyzed 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 individuals, or approximately 65% of the potential data. The main overall results (HR) were (a) time to treatment withdrawal 1.62 (95% confidence interval 1.22 to 2.14); (b) time to 12-month remission 0.93 (95% confidence interval 0.70 to 1.23) and (c) time to first seizure 0.84 (95% confidence interval 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.

Authors' 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 adverse effects.

This record should be cited as:

Taylor S, Tudur Smith C, Williamson PR, Marson AG. Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD002217. DOI: 10.1002/14651858.CD002217

Assessed as up to date:

November 11, 2009

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Primary Review Group:

Epilepsy Group

Health topics:

Neurology > Epilepsy > Drugs for broad populations

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures

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