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Differential cognitive and behavioral effects of topiramate and valproate

From the Department of Neurology (Drs. Meador and Loring), Medical College of Georgia, Augusta; and Ortho-McNeil Pharmaceutical (Drs. Hulihan, Kamin, and Karim), Raritan, NJ.

Address correspondence and reprint requests to Dr. Kimford J. Meador, Department of Neurology, Georgetown University Hospital, 1st Floor Bles, 3800 Reservoir Road, N.W., Washington, DC 20007; e-mail: kjm32{at}georgetown.edu

Objective: Cognitive effects have been reported during topiramate (TPM) treatment, but effects relative to standard antiepileptic drugs are unclear.

Methods: The authors compared TPM and valproate (VPA) added to carbamazepine (CBZ) in adults with partial seizures. A comprehensive neuropsychological test battery including cognitive, mood, and quality of life measures was used in this multicenter, randomized, double-blind study. After a 4-week baseline, study drug was titrated over 8 weeks to target dosages of 400 mg/d TPM, 2,250 mg/d VPA, or placebo and then maintained for an additional 12 weeks. The neuropsychological test battery was administered at baseline and at the end of titration and maintenance periods.

Results: Slightly more patients on TPM dropped out. Neuropsychological data at all three test periods were available for 62 patients. At the end of maintenance, effects of TPM and VPA were comparable, except for two variables (Symbol Digit Modalities Test and Controlled Oral Word Association Test), in which TPM had greater negative effects relative to VPA. The statistical differences appeared to be due in large part to a small subset of patients who were more negatively affected by TPM. Cognitive effects of TPM relative to VPA were greater at the end of titration than at the end of maintenance.

Conclusions: With adjunctive therapy at moderate dose escalation rate, the cognitive effects of TPM are slightly worse overall than VPA in patients who tolerate therapy over several months.

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