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

Abstract

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.

Ramelteon

“…The absence of motor and cognitive impairment after ramelteon ingestion in the present study contrasts with findings from previous studies demonstrating impairing effects after administration of a range of hypnotic drugs, including benzodiazepine receptor agonists (eg, zolpidem, 44 lorazepam, 46 triazolam, 35 oxazepam, 47 and zaleplon 12 ) and other compounds (eg, pentobarbital sodium, 35 diphenhydramine hydrochloride, 54 and trazodone hydrochloride 55 ). Previous results of sleep efficacy investigations of ramelteon are consistent with the present study in finding no motor or cognitive-impairing effects.…”

Neuropsychiatric Effects of Prescription Drug Abuse

“…Early investigations seemed to indicate little evidence of abuse or dependence (Darcourt et al 1999). However, several recent studies have demonstrated that these medications do have significant abuse potential (Ravishankar and Carnwath 1998;Rush et al 1999), particularly at high doses and in patients with a history of substance dependence (Hajak et al 2003;Soyka et al 2000). Withdrawal seizures have also been seen at supra-therapeutic doses (Aragona 2000).…”

Zolpidem dependence with frontal lobe syndrome: a case report

“…There is some indication that zolpidem can have an anxiolytic effect at higher doses and that with increasing dose of zolpidem for sleep can lead to withdrawal side effects during the daytime. 4 The guideline also states that the duration of treatment should usually vary from a few days to two weeks with a maximu m of four weeks, including tapering off where appropriate. 5 However, recently concern has been raised regarding the dependence potential of these Z-drugs.…”