Acute topiramate differentially affects human aggressive responding at low vs. moderate doses in subjects with histories of substance abuse and antisocial behavior

Pharmacol Biochem Behav. 2009 Apr;92(2):357-62. doi: 10.1016/j.pbb.2009.01.002.

Abstract

Anticonvulsant drugs have demonstrated efficacy in the management of irritability and aggression in a variety of psychiatric populations. We examined the acute effects of topiramate on aggression using a laboratory model of human aggression (PSAP) in individuals at high risk for aggressive and violent behavior.Twelve subjects, on parole/probation and with an Axis-II personality disorder and/or a substance use disorder, received 100, 200, 300, and 400 mg in an ascending sequence, with intervening placebo doses.Subjects participated 2-3 days per week over 4-6 weeks. Due to cognitive side effects at 300 mg, two subjects only completed through the 200 mg dose. Topiramate produced an inverted U-shaped dose response curve, with increases in aggression peaking at 200 mg and a modest decrease at 400 mg. Statistical analysis revealed a polynomial trend for dose (p=0.001). The observed inverted U-shaped function in aggressive responding is consistent with non-human aggression studies of GABA-A modulators. Acute topiramate doses >400 mg may have anti-aggressive effects, but dose levels in the 200-300 mg range may produce increases in aggression and side effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aggression / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Fructose / therapeutic use
  • Humans
  • Male
  • Social Behavior*
  • Substance-Related Disorders / drug therapy*
  • Topiramate

Substances

  • Topiramate
  • Fructose