Acute behavioral effects and abuse potential of trazodone, zolpidem and triazolam in humans

Craig R. Rush, Robert W. Baker, Ken Wright

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


The present study examined the acute behavioral effects and abuse potential of three drugs commonly used to treat sleep disorders, trazodone, zolpidem and triazolam, and placebo in ten male volunteers with histories of alcohol and drug abuse. Trazodone (100, 200 and 300 mg), a triazolopyridine antidepressant, was included because antidepressants are being used more frequently to treat sleep disorders, but it is unclear whether they have a distinct behavioral pharmacologic profile relative to benzodiazepine hypnotics. Zolpidem (15, 30 and 45 mg), an imidazopyridine hypnotic, was tested because it is the most commonly prescribed hypnotic and purportedly has a unique benzodiazepine-receptor binding profile. Triazolam (0.25, 0.5 and 0.75 mg), a triazolobenzodiazepine hypnotic, was included as the standard component because previous laboratory studies have demonstrated that it has at least some abuse potential. Trazodone, zolpidem and triazolam generally produced comparable dose-related increases in scores on the PCAG scale of the ARCI, which suggests the doses tested were equivalent on some behavioral dimension. The effects of trazodone on subject-rated items thought to measure abuse potential (e.g., subject ratings of Willing to Take Again) were less than those observed with triazolam. Zolpidem and triazolam produced comparable effects on these measures. The highest dose of zolpidem, but not triazolam, increased ratings of Like Drug, Happy, Good Effects, Friendly, Elated, Carefree and Bad Effects. Triazolam and zolpidem produced dose- dependent impairment on all of the performance tasks. Trazodone impaired performance on some, but not all, of these tasks. Consistent with the pharmacokinetics of these compounds, the time-action functions of trazodone, zolpidem and triazolam were similar on these measures. These data suggest that trazodone has less abuse potential than triazolam, and may be a viable alternative to benzodiazepine hypnotics in individuals with histories of alcohol or drug abuse. By contrast, despite its unique neuropharmacological profile, the acute behavioral effects and abuse potential of zolpidem are comparable to those of triazolam.

Original languageEnglish
Pages (from-to)220-233
Number of pages14
Issue number3
StatePublished - 1999

Bibliographical note

Funding Information:
Acknowledgements This research was supported by the National Institute on Drug Abuse Grant DA 09841 (C.R.R.). The authors are most to grateful to the ten volunteers that consented to participate in this experiment. The authors are also grateful to Richard L. Ogletree Jr, Pharm. D. for preparing the medications, and Catherine A. Hayes, BS, Josephine M. Gates, BS, Keionna N. Jiles, BS, Doris J. Wilson, BS, and Sharon C. Erwin, RN for their expert technical and nursing assistance. Finally, the authors are grateful to the entire staff of the General Inpatient Psychiatry Unit at the University of Mississippi Medical Center.


  • Abuse potential
  • Behavioral effect
  • Hypnotics
  • Trazodone
  • Triazolam
  • Zolpidem

ASJC Scopus subject areas

  • Pharmacology


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