Quazepam, sold under the brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia, including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively (and uniquely) selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines (due to its novel receptor-subtype selectivity). Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture. It was patented in 1970 and came into medical use in 1985.
Medical uses
Quazepam is used for short-term treatment of insomnia related to sleep induction or sleep maintenance problems and has demonstrated superiority over other benzodiazepines, such as temazepam. It had a lower incidence of side effects than temazepam, including less sedation, amnesia, and motor impairment. Usual dosage is 7.5 to 15 mg orally at bedtime. Quazepam is effective as a premedication prior to surgery.
Side effects Quazepam has fewer side effects than other benzodiazepines and less potential to induce tolerance and rebound effects. There is significantly less potential for quazepam to induce respiratory depression or to adversely affect motor coordination than other benzodiazepines. The different side effect profile of quazepam may be due to its more selective binding profile to type 1 benzodiazepine receptors.
Ataxia Daytime somnolence Hypokinesia Cognitive and performance impairments In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.
Tolerance and dependence Tolerance may occur to quazepam, but more slowly than seen with other benzodiazepines such as triazolam. Quazepam causes significantly less drug tolerance and withdrawal symptoms including less rebound insomnia upon discontinuation compared to other benzodiazepines. Quazepam may cause less rebound effects than other type1 benzodiazepine receptor selective nonbenzodiazepine drugs due to its longer half-life. Short-acting hypnotics often cause next-day rebound anxiety. Quazepam, due to its pharmacological profile, does not cause next-day rebound withdrawal effects during treatment. No firm conclusions can be drawn, however, about whether long-term use of quazepam does not produce tolerance, as few, if any, long-term clinical trials extending beyond 4 weeks of chronic use have been conducted. Quazepam should be withdrawn gradually if used beyond 4 weeks of use to avoid the risk of a severe benzodiazepine withdrawal syndrome developing. Very high dosage administration over prolonged periods of time, up to 52 weeks, of quazepam in animal studies provoked severe withdrawal symptoms upon abrupt discontinuation, including excitability, hyperactivity, convulsions, and the death of two of the monkeys due to withdrawal-related convulsions. More monkeys died however, in the diazepam-treated monkeys. In addition, it has now been documented in the medical literature that one of the major metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), which is long-acting and prone to accumulation, binds unselectively to benzodiazepine receptors, thus quazepam may not differ all that much pharmacologically from other benzodiazepines.
Special precautions Benzodiazepines require special precaution if used during pregnancy, in children, alcohol, or drug-dependent individuals, and individuals with comorbid psychiatric disorders. Quazepam and its active metabolites are excreted into breast milk. Accumulation of one of the active metabolites of quazepam, N-desalkylflurazepam, may occur in the elderly. A lower dose may be required for the elderly.
Elderly Quazepam is more tolerable for elderly patients compared to flurazepam due to its reduced next-day impairments. However, another study showed marked next-day impairments after repeated administration due to the accumulation of quazepam and its long-acting metabolites. Thus, the medical literature shows conflicts on quazepam's side effect profile. A further study showed significant balance impairments combined with an unstable posture after administration of quazepam in test subjects. An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines, including quazepam, the nonbenzodiazepine sedative/hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative/hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly people with chronic insomnia.
Interactions The absorption rate is likely to be significantly reduced if quazepam is taken in a fasted state, reducing the hypnotic effect of quazepam. If 3 or more hours have passed since eating food, then some food should be eaten before taking quazepam.
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