Alprazolam: Effects on Sleep and Withdrawal Phenomena

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.

Antioxidative and neuroprotective effects of Leea macrophylla methanol root extracts on diazepam-induced memory impairment in amnesic Wistar albino rat

“…Many flavonoids such as isoflavones S-(−)-equol, 4′-hydroxy-7-methoxyisoflavone and 3′,7-dihydroxyisoflavone, were found to be ligands for GABAA receptors in the CNS; which led to the hypothesis that they act as benzodiazepine-like molecules [42,43]. This is supported by their behavioral effects in animal models of anxiety, sedation and convulsion [3]. Since Leea macrophylla was found to possess flavonoids, alkaloids, tannins and terpenoids, behavioral effects in animal models of anxiety and sedation could be supported by different doses LM.…”

“…They sometimes cause sedation and myorelaxation [3]. Due to such failure of therapies in neuronal damage repair and severe adverse effects of antiamnesic drugs, alternative treatments as herbal or plant-derived drugs are increasingly being used to alleviate the affective disorders [4].…”

Interdose Elevation in Plasma Cortisol During Chronic Treatment with Alprazolam but not Lorazepam in the Elderly

“…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, 1983Kales et al, , 1987Noyes et al, 1985Noyes et al, , 1988Pecknold, 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.…”

Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement

“…On the other hand, the withdrawal from benzodiazepines, and especially those with short or intermediate duration of action, is most often accompanied by a withdrawal syndrome (Scharf et al, 1988;Gaillard et al, 1973;Johnson et al, 1976;Feinberg et al, 1977;Azumi et al, 1981;Adam et al, 1976;Kales et al, 1987). This syndrome is characterized by nightmares, a worsening of sleep disturbances and by the presence of anxiety during both the night and day.…”