Comparison of short and long half-life benzodizepine hypnotics: Triazolam and quazepam

Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.9). 09/1986; 40(4):378-386. DOI: 10.1038/clpt.1986.194


Two benzodiazepine hypnotics, triazolam, 0.25 mg, with a short elimination t1/2, and quazepam, 15 mg, with a long t1/2, were evaluated in 22-night sleep laboratory studies. Quazepam improved sleep significantly during both short- and intermediate-term use. Daytime sleepiness, which decreased with continued use, was the side effect most often associated with quazepam dosing. In contrast, triazolam dosing did not significantly improve any of the major sleep efficiency parameters, and there was a rapid development of tolerance for the drug's slight initial effectiveness. In addition, there were a number of behavioral side effects including amnesia, confusion, and disinhibition. Withdrawal of triazolam was associated with sleep and mood disturbances (rebound insomnia and rebound anxiety), whereas quazepam exerted carryover effectiveness. Thus the data in this study show that the 0.25 mg dose of triazolam, which is being prescribed increasingly, has a profile of side effects that is similar to that of the 0.5 mg dose.

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Available from: Edward Bixler, Sep 25, 2014
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    • "This can be explained by the low dose of 0.25 mg triazolam compared with 0.5 mg used in many of the previous studies. Roehrs et al. (1986) reported rebound insomnia during discontinuation of 0.5 mg of triazolam in normal sleepers but not during discontinuation of 0.25 mg, whereas Kales et al. (1986) found rebound insomnia with 0.25 mg in terms of a significant increase of total wake time for the first three nights after drug discontin- uation. Contrary to withdrawal of triazolam, we did not find significant rebound insomnia following discontinuation of zolpidem and zopiclone. "
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    ABSTRACT: Rebound effects after withdrawal from hypnotics are believed to trigger their chronic use and to enhance the risk of tolerance and dependence. It was the purpose of this study to investigate the acute polysomnographic withdrawal effects after a 4 week treatment with standard doses of the non-benzodiazepine hypnotics zopiclone and zolpidem compared with triazolam and placebo. Healthy male subjects between 22 and 35 years of age participated in a parallel study design. They received either zopiclone 7.5 mg (n=11), zolpidem 10 mg (n=11), triazolam 0.25 mg (n=10) or placebo (n=7) over 4 weeks in randomized and double-blind order. Sleep EEG was registered during 2 nights before treatment under placebo, on days 1, 27 and 28 of treatment and on days 29,30,41 and 42 under placebo. Total sleep time and sleep efficiency were lower in the 1st night after discontinuation of triazolam (p < 0.05, t-test). After withdrawal from zopiclone or zolpidem slight but not significant rebound effects concerning sleep continuity were observed. Self-rating scales showed minimal rebound insomnia after discontinuation of all three hypnotics. In the placebo group no changes of sleep parameters were observed. Assuming that rebound insomnia is part of a withdrawal reaction, this study indicates that the risks of tolerance and dependency are low when administering zopiclone or zolpidem at the recommended doses.
    Full-text · Article · Jun 2001 · European Archives of Psychiatry and Clinical Neuroscience
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    ABSTRACT: Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.
    No preview · Article · Oct 1987 · New England Journal of Medicine
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    ABSTRACT: Behavioral effects of the benzodiazepine agonist quazepam were compared with those of lorazepam in squirrel monkeys responding under a fixed-interval schedule of food presentation with a superimposed fixed-ratio schedule of response-produced shock. Low and intermediate i.v. doses of quazepam (0.1-1.0 mg/kg) and lorazepam (0.03-0.3 mg/kg) increased rates of suppressed responding, yet the maximal increases in rate were less after quazepam than after lorazepam. Higher doses of both drugs tended to increase responding less or decrease it and, with quazepam, frequent sleep was observed for 2-3 days afterwards. The dose-response curves for quazepam and lorazepam were shifted to the right following i.v. pretreatment with the benzodiazepine antagonists Ro 15-1788 (0.18-3.0 mg/kg) or AHR-11797 (1.0-5.6 mg/kg); in this regard, AHR-11797 was less potent than Ro 15-1788. Although the effects of quazepam on suppressed responding are likely due to actions at benzodiazepine receptors, these effects may be influenced by or reflect a more prominent sleep-promoting action of the drug.
    No preview · Article · Nov 1988 · European Journal of Pharmacology
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