Carbamazepine versus valproate monotherapy for epilepsy

No reliable evidence to distinguish between carbamazepine and valproate for partial onset seizures and generalized onset tonic-clonic seizures.

Epilepsy is a disorder where recurrent seizures are caused by abnormal discharges from the brain. Carbamazepine is commonly used to treat partial seizures while valproate is used for generalized seizures. The review of trials found no evidence to support the belief that valproate is superior to carbamazepine for generalized tonic-clonic seizures. While it was found that younger people fared better on valproate and older people on carbamazepine, this may be because generalized epilepsy is more common in childhood and adolescence.

Authors' conclusions: 

We have found some evidence to support the policy of using carbamazepine as the first treatment of choice in partial epilepsies, but no evidence to support the choice of valproate in generalized epilepsies, but confidence intervals are too wide to confirm equivalence. Misclassification of people with epilepsy may have confounded our results, and has important implications for the design and conduct of future trials.

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Background: 

Carbamazepine and valproate are drugs of first choice for epilepsy. Despite the lack of hard evidence from individual randomized controlled trials, there is strong clinical belief that valproate is the drug of choice for generalized epilepsies and carbamazepine for partial epilepsies.

Objectives: 

To overview the best evidence comparing carbamazepine and valproate monotherapy

Search strategy: 

We searched the Cochrane Epilepsy Group's Specialized Register (27 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 comparing carbamazepine and valproate monotherapy for epilepsy.

Data collection and analysis: 

This was an individual patient data review. Outcome measures were time to withdrawal of allocated treatment, time to 12-month remission, and time to first seizure post randomization. Data were analysed using the stratified logrank test with results expressed as hazard ratios (HR) with 95% confidence intervals (CIs), where HR > 1 indicates an event is more likely on valproate. A test for an interaction between treatment and epilepsy type (partial versus generalized) was also undertaken.

Main results: 

Results data were available for 1265 participants from five trials, representing 85% of the participants recruited into the eight trials that met our inclusion criteria. The main overall results (HR) were: time to treatment withdrawal 0.97 (95% CI 0.79 to 1.18); 12 month remission 0.87 (95% CI 0.74 to 1.02); first seizure 1.09 (95% CI 0.96 to 1.25) suggesting no overall difference for these outcomes. The test for an interaction between treatment and epilepsy type was non significant for time to treatment withdrawal and 12-month remission, but significant for time to first seizure. The age distribution of adults classified as having a generalized epilepsy indicate that significant numbers of individuals may have had their epilepsy misclassified.

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