A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures
Ap. Aldenkamp et al., A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures, EPILEPSIA, 41(9), 2000, pp. 1167-1178
Purpose: This study compares the cognitive effects of topiramate (TPM) with
those of valproate (VPA) using efficacious doses of each drug when used as
adjunctive therapy to carbamazepine (CBZ). A key question of the study is
to what extent a more gradual introduction of TPM improves tolerability and
prevents cognitive impairment.
Methods: The study is a multicenter, randomized, observer-blinded, parallel
-group clinical trial with VPA or TPM given as first-line add-on therapy to
steady-state treatment with CBZ. TPM is introduced at 25 mg and increased
with weekly 25-mg/d increments to a minimum dosage of 200 mg/d. The target
dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The st
udy evaluates cognitive function changes from baseline to end point (after
20 weeks of treatment) and during titration (after 8 weeks of treatment). T
he primary outcome measure is the difference between the treatments (TPM ve
rsus VPA) in change from baseline to end point and change from baseline to
titration, using a 95% confidence interval approach.
Results: For the 10 baseline-to-end point comparisons, one test measuring s
hort-term verbal memory (Rey Auditory Verbal Learning Test) yields a statis
tically significant difference between the treatments (p = 0.02), showing w
orsening for TPM and improvement of scores for VPA. The 10 baseline-to-titr
ation comparisons also show one statistically significant difference, again
for a test measuring short-term memory (Recognition of Words; p = 0.04), s
howing a larger change in the negative direction for TPM. None of the mood
tests or the test for subjective complaints shows statistically significant
differences between the treatments, although more scores are in the negati
ve direction for TPM during titration.
Conclusion: Although the pattern of changes in the negative direction seems
consistent with clinical information, the differences found between the tr
eatments are small. An important finding of our study is that, when the res
ults are compared with those of other studies, it is clear that gradual int
roduction of TPM can reduce the extent of cognitive impairment (with a maxi
mum of about 0.6 SD).