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Evidence based medicine:
Carbamazepine vs. valproate monotherapy
for epilepsy
K. Wehrens, M. van Nieuwenhoven
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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.
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Aim:
To overview the best evidence comparing
carbamazepine and valproate monotherapy.
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Search strategy
The Cochrane Epilepsy Group trials register (27
June 2003); the Cochrane Central Register ofControlled Trials
(The Cochrane Library issue 2,
2003) and MEDLINE (27 June 2003).
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Selection criteria:
Randomized controlled trials comparing
carbamazepine and valproate monotherapy forpartial and
generalized epilepsy.
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Outcome measures:
Outcome measures: Time to withdrawal ofallocated 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 advantagefor
carbamazepine, and for time to 12 month
remission (or first seizure) a HR>1 indicates a
clinical advantage for valproate.
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Results:
Results data were available for 1265 participants from
5trials.
(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.
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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% CI0.96 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
asignificant advantage for carbamazepine in people with
partial epilepsy.
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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 importantadvantage 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.
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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
