The effects of phenytoin on impulsive and premeditated aggression: a controlled study

Studies of the effects of phenytoin on aggression have produced equivocal results primarily because of a lack of (1) common objective criterion measures of aggressive acts across studies; (2) rigorous inclusion and exclusion criteria for selecting subjects; and (3) a nosologic basis for classifying different types of aggression. The current study was designed to remedy these deficiencies. Aggression was defined using a nosology that defines three types of aggression: (1) medically related; (2) premeditated; and (3) impulsive. The purpose of this study was to test the hypothesis that phenytoin will decrease impulsive aggressive acts but not have a significant influence on premeditated aggressive acts. Sixty inmates were divided into two groups on the basis of committing primarily impulsive aggressive acts or premeditated aggressive acts while in prison. Medical aggression was ruled-out by subject selection. The study used a double-blind, placebo-controlled, crossover design. As hypothesized, phenytoin (200 mg a.m. and 100 mg p.m.) significantly reduced impulsive aggressive acts but not premeditated aggressive acts. Event-related potentials (ERPs) measured information processing in the cortex during drug/placebo conditions. The amplitudes of P300 ERP waveforms among impulsive aggressive subjects were increased significantly during the phenytoin condition but not during the placebo condition. There were no significant changes in P300 ERP waveforms between drug/placebo conditions among nonimpulsive aggressive subjects.