A double-blind placebo-controlled crossover study of phenytoin in individuals with impulsive aggression

Psychiatry Res. 2001 Sep 20;103(2-3):193-203. doi: 10.1016/s0165-1781(01)00287-6.


The present study examines the behavioral and psychophysiological effects of phenytoin (PHT) in individuals who display impulsive-aggressive outbursts. In a double-blind placebo-controlled crossover design, individuals meeting previously established criteria for impulsive aggression were administered PHT and placebo during separate 6-week conditions. The efficacy measures used were the Overt Aggression Scale (OAS) and the Profile of Mood States (POMS). Psychophysiological measures (evoked potentials) were taken at baseline and at the end of each 6-week condition. Photic stimulation was used to evoke the mid-latency P1-N1-P2 waveform complex. Analysis indicated a significant decrease in the frequency of impulsive-aggressive outbursts during PHT administration compared to baseline and placebo. Analysis of the psychophysiological data showed significantly increased P1 amplitude and significantly longer N1 latency during PHT administration. In addition, a reduction in N1 amplitude during PHT administration was also suggested. These findings indicate reparation of physiological abnormalities previously observed in impulsive-aggressive individuals and imply more efficient sensory processing and effective orienting of attention. Taken together, these results provide insight as to the physiological mechanisms by which PHT serves to ameliorate impulsive-aggressive behavior.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aggression / drug effects*
  • Cerebral Cortex / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography / drug effects
  • Humans
  • Impulsive Behavior / diagnosis
  • Impulsive Behavior / drug therapy*
  • Impulsive Behavior / parasitology
  • Male
  • Middle Aged
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use*


  • Phenytoin