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Evidence based medicine: Carbamazepine vs. valproate monotherapy for epilepsy

Evidence based medicine: Carbamazepine vs. valproate monotherapy for epilepsy K. Wehrens, M. van Nieuwenhoven. Background:

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Evidence based medicine: Carbamazepine vs. valproate monotherapy for epilepsy

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  1. Evidence based medicine: Carbamazepine vs. valproate monotherapy for epilepsy K. Wehrens, M. van Nieuwenhoven

  2. 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.

  3. Aim: To overview the best evidence comparing carbamazepine and valproate monotherapy.

  4. Search strategy The Cochrane Epilepsy Group trials register (27 June 2003); the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 2, 2003) and MEDLINE (27 June 2003).

  5. Selection criteria: Randomized controlled trials comparing carbamazepine and valproate monotherapy for partial and generalized epilepsy.

  6. Outcome measures: Outcome measures: Time to withdrawal of allocated treatment; Time to 12 month remission; Time to first seizure post randomization. Results are expressed as hazard ratios (HR), and by convention a HR>1 indicates that an event is more likely on valproate. Hence for treatment withdrawal a HR>1 indicates a clinical advantage for carbamazepine, and for time to 12 month remission (or first seizure) a HR>1 indicates a clinical advantage for valproate.

  7. Results: Results data were available for 1265 participants from 5 trials. (1) Time to treatment withdrawal: No overall difference in treatment effect was found between carbamazepine and valproate. The estimated overall hazard ratio (HR) with 95% confidence interval (CI) was 0.97(95% CI 0.79 to 1.18), adjusted for epilepsy type, suggesting no clear clinical advantage for either drug. Results stratified for epilepsy type give a summary HR 0.89(95% CI 0.61 to 1.29) for generalized epilepsy, and 1.00(95% CI 0.79 to 1.26) for partial epilepsy.

  8. Results: (2) Time to first seizure: There was no statistically significant heterogeneity, and no overall difference in treatment effect was found. The estimated HR, adjusted for epilepsy type, was 1.09(95% CI 0.96 to 1.25) suggesting a small but clinically important advantage in favour of carbamazepine. Results stratified for epilepsy type give a summary HR of 0.86(95% CI 0.68 to 1.09) for generalized epilepsy, and 1.22(95% CI 1.04 to 1.44) for partial epilepsy, indicating a significant advantage for carbamazepine in people with partial epilepsy.

  9. Results: (3) Time to 12 months remission: No difference in overall treatment effect was found and the estimated HR was 0.87(95% CI 0.74 to 1.02), adjusted for epilepsy type, suggesting a potentially important advantage to carbamazepine. Results stratified for epilepsy type give a summary HR of 0.96(95% CI 0.75 to 1.24) for generalized epilepsy, and 0.82(95% CI 0.67 to 1.00) for partial epilepsy.

  10. Conclusions: Some evidence to support the policy of using carbamazepine as the first treatment of choice in partial epilepsies. 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 the results

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