Alprazolam: Effects on Sleep and Withdrawal Phenomena

Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey.
The Journal of Clinical Pharmacology (Impact Factor: 2.48). 07/1987; 27(7):508-15. DOI: 10.1002/j.1552-4604.1987.tb03058.x
Source: PubMed


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.

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    • "Alprazolam exhibits a similar side-effect profile to other benzodiazepines (Ballenger et al., 1988; O'Sullivan et al., 1994; Verster and Volkerts, 2004).An investigation of adverse effects recorded in the CNCPS II trial (Cassano et al., 1994) demonstrated significantly increased rates of sedation (44% vs. 16%), fatigue/weakness (18% vs. 12%) and memory problems (15% vs. 9%) (Cassano et al., 1994) with alprazolam over placebo at week 4.Other reviews (Jonas and Cohon, 1993) and reports from major studies (Ballenger et al., 1988; O'Sullivan et al., 1994) also report significant side effects with alprazolam use including irritability , poor concentration, slurred speech, decreased appetite and weight loss. Alprazolam can lead to rebound insomnia, with rapid tolerance developed to short-term sleep-inducing effects (Kales et al., 1987). Most side effects were most prominent early in treatment, decreased throughout treatment courses but were maintained above placebo in long-term studies (Andersch and Hetta, 2003, Pollack et al., 1993; Rickels and Schweizer, 1998). "
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    ABSTRACT: To investigate the potential impact of increasing prescription rates of alprazolam for the treatment of panic disorder (PD) in Australia through a review of efficacy, tolerability and adverse outcome literature. Data were sourced by a literature search using MEDLINE, Embase, PsycINFO and a manual search of scientific journals to identify relevant articles. Clinical practice guidelines from the American Psychiatric Association, National Institute of Clinical Excellence, Royal Australian and New Zealand College of Psychiatrists and World Federation of Societies of Biological Psychiatry were sourced. Prescription data were sourced from Australian governmental sources. Alprazolam has shown efficacy for control of PD symptoms, particularly in short-term controlled clinical trials, but is no longer recommended as a first-line pharmacological treatment due to concerns about the risks of developing tolerance, dependence and abuse potential. Almost no evidence is available comparing alprazolam to current first-line pharmacological treatment. Despite this, prescription rates are increasing. A number of potential issues including use in overdose and impact on car accidents are noted. conclusion: Although effective for PD symptoms in clinical trials, a number of potential issues may exist with use. Consideration of its future place in PD treatment in Australia may be warranted.
    Full-text · Article · Mar 2012 · Australian and New Zealand Journal of Psychiatry
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    • "Thus, given the relatively short elimination half-life of alprazolam and a prolonged interdose interval, it is possible that a marked drop in plasma drug concentration could trigger increased HPA axis activity in the period prior to morning dose. Indeed, clinical data from individuals on chronic treatment with alprazolam and similar BZPs suggest that rebound anxiety and other symptoms of withdrawal reactions can develop between doses (Ashton, 1994; Cole and Kando, 1993; Hallstrom and Lader, 1981; Herman et al, 1987; Kales et al, 1983, 1987; Noyes et al, 1985, 1988; Pecknold, 1993; Risse et al, 1990; Schweizer and Rickels, 1998; Slak, 1986; Vgontzas et al, 1995; Woods et al, 1992; Wolf and Griffiths, 1991). However, it appears that none of these studies have examined interdose plasma cortisol levels. "
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    ABSTRACT: Benzodiazepines (BZPs) have been shown to reduce hypothalamic-pituitary-adrenal (HPA) axis activity acutely in normal humans. In contrast, the effects of chronic BZP treatment on the HPA axis have not been well studied, especially in the geriatric population. This study examined the acute and chronic effects (3 weeks) of alprazolam and lorazepam on plasma cortisol in 68 subjects (60-83 years) who received 0.25 or 0.50 mg b.i.d. alprazolam, or 0.50 or 1.0 mg b.i.d. lorazepam, or placebo orally according to a randomized, double-blind, placebo-controlled parallel design. Memory assessment and blood samples for plasma cortisol were obtained prior to the morning dose on days 0, 7, 14, and 21, and at 1, 2.5, and 5 h postdrug on days 0 and 21. Assessments of anxiety and depression were carried out at days 0, 7, 14, and 21 before drug administration. Plasma cortisol was affected compared to placebo only by the 0.5 mg alprazolam dose. During the first and the last day of treatment, there was a significant drop in cortisol at 2.5 h after alprazolam compared to placebo. The predose cortisol levels increased significantly during chronic alprazolam treatment, and correlations were found between these cortisol changes and changes in depression, anxiety, and memory scores. These findings suggest that even a short period of chronic treatment with alprazolam, but not lorazepam, may result in interdose HPA axis activation in the elderly, consistent with drug withdrawal. If confirmed, this effect may contribute to an increased risk for drug escalation and dependence during chronic alprazolam treatment.
    Full-text · Article · Apr 2004 · Neuropsychopharmacology
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    ABSTRACT: In this single-blind study the sedative and hypnotic properties of buspirone, a nonbenzodiazepine anxiolytic, were investigated in 8 anxious outpatients. Polysomnographic recordings were gathered during baseline, at the start of active medication, after 3 weeks of treatment and one night after discontinuing treatment. Daytime alertness was measured using the Multiple Sleep Latency Test and performance tests. The effects of buspirone on sleep structure were minimal and of no clinical consequence. Subjectively, the patients reported improved sleep quality. There were no effects on daytime alertness at the beginning, after 3 weeks or at sudden discontinuation of the medication. It is concluded that buspirone does not have a sedative or hypnotic effect in anxiety patients.
    No preview · Article · Mar 1989 · Acta Psychiatrica Scandinavica
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