Differential cognitive and behavioral effects of topiramate and valproate.
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.
Department of Neurology, Medical College of Georgia, Augusta, USA. kjm32@georgetown.edu
K J
KJ
Meador
D W
DW
Loring
J F
JF
Hulihan
M
M
Kamin
R
R
Karim
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001288:Attention / Q000187:drug effects; D001519:Behavior / Q000187:drug effects*; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D011788:Quality of Life; D000077236:Topiramate; D014635:Valproic Acid / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D014635:Valproic Acid