Impulsiveness as a predictor of topiramate response for cocaine use disorder

Am J Addict. 2019 Feb;28(2):71-76. doi: 10.1111/ajad.12858. Epub 2019 Jan 21.


Background/objectives: Topiramate has been studied in the treatment of substance use disorders and is often used off-label in the treatment of other disorders with impaired impulse control. We sought to determine whether impulsiveness could predict topiramate treatment response in individuals with cocaine use disorder (CUD).

Methods: In a post-hoc analysis of a 12-week, double-blind, randomized, placebo-controlled trial of topiramate for CUD, we examined the relationship between response to treatment and participants' baseline score on the Barrett Impulsiveness Scale (BIS-11). During the original trial, topiramate was titrated up to 300 mg/day over 6 weeks and maintained for 6 weeks. All participants received weekly cognitive behavioral therapy.

Results: Individuals with total BIS-11 scores above the median had 11.2% more cocaine-free days with topiramate versus placebo (Bonferroni corrected p = 0.047). Individuals with first-order factor scores above the median in self-control (Bonferroni corrected p = 0.020) and at or below the median in attention (Bonferroni corrected p = 0.022), and second-order factor scores at or below the median in attentional (Bonferroni corrected p = 0.024) and motor impulsiveness (Bonferroni corrected p = 0.046) were all associated with a greater improvement with topiramate.

Discussion/conclusion: The results indicate an association between higher within-group impulsiveness and response to topiramate for CUD. The subscore findings may suggest a complex interaction between effectiveness and known cognitive side effects. The finding that trait impulsiveness is associated with treatment response is a promising discovery that may help guide treatment for CUD.

Scientific significance: This analysis suggests a possible endophenotype based on impulsiveness that can predict treatment response to topiramate. (Am J Addict 2019;XX:1-6).

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects
  • Cocaine-Related Disorders* / psychology
  • Cocaine-Related Disorders* / therapy
  • Cognitive Behavioral Therapy / methods
  • Double-Blind Method
  • Female
  • Humans
  • Impulsive Behavior / drug effects*
  • Male
  • Middle Aged
  • Patient Selection
  • Psychological Techniques
  • Self-Control / psychology*
  • Topiramate* / administration & dosage
  • Topiramate* / adverse effects
  • Treatment Outcome


  • Anticonvulsants
  • Topiramate