Reintroduction of quazepam: an update on comparative hypnotic and adverse effects

Insomnia is a prevalent disorder that affects over one-third of the U.S. population to varying degrees and is highly disruptive towards quality of life. Pharmacological treatments for insomnia include benzodiazepines (BZs) and the non-BZ 'Z-drugs' (zolpidem, zaleplon, eszopiclone, zopiclone), which are amongst the most widely prescribed medications. Yet, these agents can produce adverse effects such as tolerance to the hypnotic effect, rebound insomnia, next-day residual drowsiness, as well as amnesia and complex behaviours such as sleep-walking, sleep-eating and sleep-driving. Quazepam, one of the five BZ approved for treatment of insomnia, was recently relaunched to the U.S. market in 2016 and is distinguished amongst hypnotic BZ by unique pharmacological characteristics including selectivity for sleep-promoting α1-subunit containing γ-aminobutyric acid (GABA-A) receptors and a significantly lower relative receptor binding affinity. These features likely drive the decreased rate of adverse events seen clinically with quazepam, such as tolerance, rebound insomnia and amnesic behaviours, compared with other BZ. Given the recent reintroduction of quazepam as a pharmacotherapeutic option, and the lack of head-to-head comparative trials against newer agents, the purpose of this review is to provide an update on distinguishing features of quazepam with regard to its pharmacology, pharmacokinetics, sleep efficacy and potential adverse effects compared to other agents used for insomnia.