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

Citation
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
Citations number
28
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EPILEPSIA
ISSN journal
00139580 → ACNP
Volume
41
Issue
9
Year of publication
2000
Pages
1167 - 1178
Database
ISI
SICI code
0013-9580(200009)41:9<1167:AMRCST>2.0.ZU;2-Q
Abstract
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).