Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures

Tudur Smith C, Marson AG, Williamson PR

Published Online:

October 7, 2009

No evidence to suggest any difference between the drugs phenytoin and valproate for the seizure types studied.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Phenytoin and valproate are commonly used antiepileptic drugs. The review of trials found no difference between these two drugs for the seizure types studied. The review also found no evidence to support the policy of using valproate for generalized onset tonic-clonic seizures and phenytoin for partial onset seizures. We were unable to address the issue of preferring valproate for generalized onset seizure types other than tonic-clonic.

Abstract (click to read)

Background:

Phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, or generalized onset seizures with or without other generalized seizure types.

Objectives:

To review the best evidence comparing phenytoin and valproate 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 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007) and MEDLINE (1966 to July 2007). No language restrictions were imposed. We also contacted pharmaceutical companies and 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 phenytoin monotherapy with valproate 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 stratified logrank analysis with results expressed as hazard ratios (HR) and 95% confidence intervals (95% CI), where a HR greater than one indicates an event is more likely on phenytoin.

Main results:

Data were available for 669 individuals from five trials, representing 60% of the participants recruited into the eleven trials that met our inclusion criteria. One important limitation is that in four of the five trials, for people classified as having generalized onset seizures, tonic-clonic seizures were the only seizure types recorded at follow up. Hence results apply only to generalized tonic-clonic seizures. The main overall results were as follows (HR, HR greater than one indicates a clinical advantage for phenytoin for both remission outcomes and a clinical advantage for valproate for the outcomes time to withdrawal and time to first seizure): (a) time to withdrawal of allocated treatment 1.10 (95% CI 0.79 to 1.54); (b) time to 12 month remission 1.04 (95% CI 0.78 to 1.38); (c) time to six month remission 0.89 (95% CI 0.71 to 1.11) and (d) time to first seizure 0.92 (95% CI 0.74 to 1.14). The results suggest no overall difference between the drugs for these outcomes. No statistical interaction between treatment and seizure type (partial versus generalized) was found.

Authors' conclusions:

We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. Results do not apply to absence or myoclonus. No outright evidence was found to support or overthrow current treatment policies.

This record should be cited as:

Tudur Smith C, Marson AG, Williamson PR. Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD001769. DOI: 10.1002/14651858.CD001769

Assessed as up to date:

July 27, 2007

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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

Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures

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