Cognitive and behavioral effects of topiramate (TPM) and valproate (VPA) as adjunctive therapy with carbamazepine (CBZ) were compared in 62 adults (16 to 55 years old) with refractory partial seizures, in a randomized, double-blind trial at the Medical College of Georgia, Augusta. After a 4-week baseline, the study drug was titrated over 8 weeks to target dosages of 400 mg/d TPM, 2250 mg/d VPA, or placebo and then maintained for an additional 12 weeks. Neuropsychological test battery was administered at baseline and at end of titration and maintenance periods. Cognitive deficits associated with TPM relative to VPA were greater at the end of titration than at the end of maintenance. The majority of patients tolerated TPM without cognitive side effects. The statistical differences were due mainly to a small subset of patients who were more negatively affected by TPM. 
COMMENT. In early trials of TPM, psychomotor slowing, memory impairment, attention deficits, confusion, and speech problems were reported in 20% of adults with partial seizures . The TPM-associated cognitive deficits appeared to be related to a rapid escalation of the dosage. Deficits in cognition may be diminished by a more gradual introduction of TPM and by testing after more prolonged usage. Monotherapy is less likely to induce cognitive problems than addon therapy.