Effects of removal of phenytoin, carbamazepine, and valproate on cognitive function

Changes in cognitive function were noted in a double-blind, prospective, placebo-controlled study of discontinuation of phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) in 58 patients with active epilepsy, receiving multiple antiepileptic drugs (AEDs). A control group of 25 patients continued with existing therapy. A simple test battery, which would be directly applicable to a clinical setting, with measures of mental speed, attention, performance of a learned skill, short-term memory, concentration, and simple coordinated hand movements was used. Cognitive assessments were made before and at the end of discontinuation of a drug and 4 weeks later. Simple motor skills became faster on discontinuation of PHT, CBZ, and VPA (p less than 0.0005), with a further improvement in the subsequent 4 weeks (p = 0.03) and no significant difference between the AEDs. Performance on a measure of attention and concentration improved on discontinuation of PHT (p = 0.005) and did not alter with removal of CBZ or VPA; the improvement in the PHT discontinuation group was significantly different from that in the control group (p = 0.001). These results suggest that all three AEDs studied may adversely affect motor function and that PHT may be more deleterious to function in higher cognitive tasks than in CBZ or VPA.