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

Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.39). 09/1986; 40(4):378-386. DOI: 10.1038/clpt.1986.194

ABSTRACT 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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    ABSTRACT: Insomnia is defined as the inability to get the amount or quality of sleep necessary for optimal functioning and well being. Long term or chronic insomnia has been conventionally considered to be that lasting for at least 21 to 30 nights; however, it usually persists for months or years. It is more frequent in women than in men, and becomes more pronounced with age. Chronic insomnia is associated with mental disorders, psychophysiological conditions, inadequate sleep hygiene, neurological disorders and drug dependency. The most prevalent diagnosis is chronic insomnia associated with psychiatric disorders, followed in precedence by psychophysiological conditions. In chronic psychophysiological insomnia, idiopathic insomnia and insomnia associated with generalised anxiety, nonpharmacological strategies and sleeppromoting medication (e.g. hypnotics) are indicated. In patients with chronic insomnia associated with major depressive disorders, antidepressants that induce acute sedation (e.g. amitriptyline, doxepin, trazodone) represent the primary drug treatments of choice. When necessary, hypnotics can be added. Currently used hypnotics include benzodiazepine derivatives, the cyclopyrrolone zopiclone and the imidazopyridine zolpidem. Hypnotics with a short halflife show the best profile of efficacy versus adverse effects with regard to morning awakening and daytime functioning. In patients with chronic insomnia, hypnotics reduce sleep-onset latency, decrease the number of nocturnal awakenings and reduce the time spent awake. The increase in total sleep time is related to greater amounts of non-rapid eye movement (NREM) sleep. Few differences exist between benzodiazepines, zopiclone and zolpidem in terms of effectiveness in inducing and maintaining sleep. However, in contrast to the benzodiazepines and zopiclone, zolpidem does not suppress slow-wave sleep. Sleep laboratory and clinical studies tend to indicate that benzodiazepines are only effective when administered for relatively short periods of time in patients with chronic insomnia. Furthermore, a rebound insomnia has been described for short- and intermediate-acting benzodiazepines and zopiclone, and a withdrawal syndrome, denoting the presence of psychological and physical dependence, follows the abrupt cessation ofbenzodiazepine administration. In contrast, no evidence of tolerance or rebound insomnia has been observed in relation to zolpidem administration.
    CNS Drugs 09/1995; 4(3):182-194. DOI:10.2165/00023210-199504030-00003 · 4.38 Impact Factor
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    ABSTRACT: Benzodiazepines are generally considered safer than previously used sedatives and hypnotics (e.g. opiates and barbiturates). In the past decade, however, they have generated considerable controversy. Although much of the ongoing debate about benzodiazepines tends to centre on issues related to their dependency and abuse potential, problems also may occur with their therapeutic use. Despite a lack of study evidence demonstrating that benzodiazepines have continuing therapeutic efficacy beyond 6 months for anxiety and 4 weeks for insomnia, an unknown number of patients have taken benzodiazepines for extended periods, in some cases for up to 25 years or more. Other than increased risk of withdrawal reactions, little is known about the effects of protracted benzodiazepine use on health and cognitive function. A number of investigators, however, have reported considerable ill health, both mental and physical, in long-term users. Short-term therapeutic use of benzodiazepines is often considered relatively risk-free. Problems, however, also may occur with brief administration of some benzodiazepines, particularly alprazolam and triazolam. Although no new class of drugs has emerged as a clear replacement of benzodiazepines, several compounds are under investigation. In the meantime, physicians must use benzodiazepines judiciously and become adept at selecting from a range of available pharmacologic and non-pharmacologic alternatives.
    International Review of Psychiatry 07/2009; 2(3-4):385-398. DOI:10.3109/09540269009026608 · 1.80 Impact Factor
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    ABSTRACT: In three parallel groups, brief and intermittent administration and withdrawal of triazolam, 0.5 mg, temazepam, 30 mg, and placebo were assessed in a 12-night sleep laboratory study of 18 subjects with insomnia. With this intermittent schedule both drugs improved sleep, with about a one-third reduction in total wake time; this reduction was significant for temazepam but not for triazolam. Even though the periods of drug administration were quite brief, withdrawal of triazolam consistently produced rebound insomnia, with increases in total wake time above baseline of 61% and 51%, respectively, for the first night of each withdrawal period. With temazepam this effect was more variable, with total wake time increased only with the second withdrawal period (39%). Thus these findings indicate that even under conditions of brief, intermittent use and withdrawal, triazolam and, to a lesser degree, temazepam produce rebound insomnia after abrupt withdrawal, thereby predisposing to drug-taking behavior and increasing the potential for drug dependence.
    Clinical Pharmacology &#38 Therapeutics 03/1991; 49(4):468-476. DOI:10.1038/clpt.1991.55 · 7.39 Impact Factor

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