Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature

Abstract

Alprazolam is a benzodiazepine derivative that is currently used in the treatment of generalized anxiety, panic attacks with or without agoraphobia, and depression. Alprazolam has a fast onset of symptom relief (within the first week); it is unlikely to produce dependency or abuse. No tolerance to its therapeutic effect has been reported. At discontinuation of alprazolam treatment, withdrawal and rebound symptoms are common. Hence, alprazolam discontinuation must be tapered. An exhaustive review of the literature showed that alprazolam is significantly superior to placebo, and is at least equally effective in the relief of symptoms as tricyclic antidepressants (TCAs), such as imipramine. However, although alprazolam and imipramine are significantly more effective than placebo in the treatment of panic attacks, Selective Serotonin Reuptake Inhibitors (SSRIs) appear to be superior to either of the two drugs. Therefore, alprazolam is recommended as a second line treatment option, when SSRIs are not effective or well tolerated. In addition to its therapeutic effects, alprazolam produces adverse effects, such as drowsiness and sedation. Since alprazolam is widely used, many clinical studies investigated its cognitive and psychomotor effects. It is evident from these studies that alprazolam may impair performance in a variety of skills in healthy volunteers as well as in patients. Since the majority of alprazolam users are outpatients, this behavioral impairment limits the safe use of alprazolam in patients routinely engaged in potentially dangerous daily activities, such as driving a car.

A method for determining the magnitude of change across different cognitive functions in clinical trials: the effects of acute administration of two different doses alprazolam

“…The absence of impairment on other tasks indicates that decisions made on the basis of material remembered over very short (working memory task) or long (learning task) periods of time, or which required ongoing problem solving (the spatial working memory task that required the subjects to learn a complex hidden maze over successive trials) were not affected at the low dose. In a recent review of alprazolam and cognitive function studies it was found that very few comparisons (approx 10%) have yielded cognitive impairment at 0.5 mg doses (Verster and Volkerts, 2004). In the current study, the impairment associated with the higher dose of alprazolam (1 mg) was generalized across all aspects of cognitive function assessed, although the magnitude of impairment did differ between tasks.…”

“…Alprazolam induces anxiolytic effects by facilitating the binding of GABA to GABAergic receptors. This action occurs non-selectively across brain structures and results in sedation (Verster and Volkerts, 2004). Although many studies have investigated the effects of alprazolam on different cognitive functions, this study is the first to directly compare the effects across a range of cognitive functions.…”

“…For treatment of panic disorder, doses up to 10 mg/day may be required. In studies using single doses ranging from 0.25 to 2.0 mg in healthy adults, alprazolam related impairment has been observed in psychomotor, attentional, executive and memory functions, although these become more robust for single doses over 1 mg (Verster and Volkerts, 2004). In the current study, therefore performance was compared between alprazolam at two single doses (0.5 mg and 1 mg) and placebo across these same cognitive domains using the CogState test battery (Falleti et al, 2003;Collie et al, 2003b) and the Groton maze learning test (GMLT; Schroder et al, 2004).…”

Synthesis, Characterization and Antimicrobial Activities of some Novel 3-(4-Bromobenzyl)-5-(Thiophen-2-yl)-4H-1,2,4-Triazol Derivatives

“…The triazole derivatives also used as potent hypnotic agents. This type of derivatives are fused triazole at 1,2-position of 1,4-benzodiazepines to give Estrazolam(14) [23], Triazolam(15) [24] and Alprazolam(16) [25]. The triazole derivatives also used as anti diabetic [29] like Sitagliptin(17) [26,27], anti HIV agent like Maraviroc (18) [28], anticancer agents [30],antioxident [32] and antibacterial [33].…”

Alprazolam Dependence – The Sting in the Tail: A Case Report

“…Withdrawal symptoms or rebound symptoms may occur after ceasing treatment abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction (10,11).…”