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Background:   Being a nonbenzodiazepine, zolpidem is believed to have a favorable side-effect profile and is widely prescribed for insomnia. However, in the past few years, numerous neuropsychiatric adverse reactions, particularly complex sleep behaviors (CSBs), have been reported with zolpidem.Objective:   To conduct a systematic review of zolpidem-associated CSBs.Data Sources:   An electronic search was conducted using MEDLINE, Embase, PubMed, and Cochrane database of systematic reviews to extract relevant articles till July 2020.Study Eligibility Criteria:   Any type of literature article (case report, case series, and observational or interventional study) reporting CSBs associated with zolpidem.Results:   In this review, we present aggregate summarized data from 148 patients presenting with zolpidem-induced CSBs (79 patients from 23 case reports and 5 case series; 69 patients out of 1454 taking zolpidem [4.7%] from three observational clinical studies). Various types of CSBs associated with zolpidem were reported, most common being sleepwalking/somnambulism and sleep-related eating disorder. On causality assessment, around 88% of cases were found to have a probable association with zolpidem.Limitations:   Extraction of data from observational studies and spontaneous reports, due to nonavailability of any randomized controlled trials relevant to the study objective.Conclusion and Implication of Key Findings:   Zolpidem-induced CSBs, although not very common, may develop when the drug is used at therapeutic doses for insomnia. Doctors need to be alert to monitor such adverse effects of zolpidem and exercise caution while prescribing it.

Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors