Alprazolam: Effects on Sleep and Withdrawal Phenomena

Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey.
The Journal of Clinical Pharmacology (Impact Factor: 2.47). 07/1987; 27(7):508-15. DOI: 10.1002/j.1552-4604.1987.tb03058.x
Source: PubMed

ABSTRACT Alprazolam was evaluated in chronic insomniacs in a 1-mg bedtime dose. The 16-night sleep laboratory protocol included four placebo-baseline nights followed by seven nights of drug administration and five placebo-withdrawal nights. On the first three drug nights (nights 5 to 7), the drug was highly effective in inducing and maintaining sleep with this short-term use. By the end of the one week of administration (nights 9 to 11), however, the drug had lost about 40% of its efficacy. During drug use, one subject reported some difficulty in controlling expression of inappropriate emotions when interacting with others, which suggested the presence of disinhibition. On the third night following drug termination, there was a significant increase in sleep difficulty above baseline levels (rebound insomnia). This worsening was of comparable magnitude to the peak improvement of sleep with drug administration. Thus, the clinical utility of alprazolam when administered to insomniac patients appears to be limited because of a relatively rapid development of tolerance and possible disinhibitory reactions during drug use and the occurrence of rebound insomnia following withdrawal.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Benzodiazepines (BDZs) are the most widely prescribed class of psychoactive drugs in current therapeutic use, despite the important unwanted side-effects that they produce such as sedation, myorelaxation, ataxia, amnesia, ethanol and barbiturate potentiation and tolerance. Searching for safer BDZ-receptor (BDZ-R) ligands we have recently demonstrated the existence of a new family of ligands which have a flavonoid structure. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have shown to possess a selective and relatively mild affinity for BDZ-Rs and a pharmacological profile compatible with a partial agonistic action. In a logical extension of this discovery various synthetic derivatives of those compounds, such as 6,3′-dinitroflavone were found to have a very potent anxiolytic effect not associated with myorelaxant, amnestic or sedative actions. This dinitro compound, in particular, exhibits a high affinity for the BDZ-Rs (Ki = 12–30 nM). Due to their selective pharmacological profile and low intrinsic efficacy at the BDZ-Rs, flavonoid derivatives, such as those described, could represent an improved therapeutic tool in the treatment of anxiety. In addition, several flavone derivatives may provide important leads for the development of potent and selective BDZ-Rs ligands.
    Neurochemical Research 05/1997; 22(4). DOI:10.1023/A:1027303609517 · 2.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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