The Z-Drugs and Their Association with Suicidality, Mortality, and Overdose: A Systematic Review
Introduction: A link has been suggested between the use of sedative-hypnotic medications and all-cause mortality, particularly accidental death and suicide. The "z-drugs" (zolpiedem, zaleplon, eszopiclone zopiclone) are non-benzodiazepines that aid in the initiation of sleep by acting on gamma-aminobutyric acid-alpha receptors. Z-drug mechanisms suggestive of suicidality may include: 1) decreased inhibition for acting on impulsive thought, 2) agitation after discontinuation, 3) depression of the central nervous system, 4) and the indication, insomnia. This systematic review examines the potential effects of the z-drugs on suicidal ideation and behavior, traumatic injury, mortality, and accidental poisoning.
Methods: On June 20, 2015 a systematic literature review of the PsycINFO and PubMed databases was conducted using the following search term: [(zopiclone OR zolpidem OR zaleplon OR eszopiclone) AND (suicide OR suicidal OR traumatic injury OR mortality OR drug overdose)]. Articles were included if they were available in English, reported human subjects data, original research or analyses of population-based datasets, and included z-drug utilization and at least one of the outcomes of interest as listed in the search terms. Included articles were used to identify additional articles through references.
Results: Of 178 abstracts, 147 were excluded if they were: not original research, a case study, a duplicate, or did not report target outcome, z-drug usage, or data allowing interpretation of this relationship. The review covered 31 studies and overall suggested a possible association between exposure to z-drugs, particularly if used outside of clinical guidelines, and increased risk of mortality, drug overdose, and traumatic injury.
Conclusion: Z-drugs have demonstrated utility as a sleep aid and may be important in reducing overall mortality associated with sleep disturbance. Yet, they have been associated with increased somnolence and traumatic injury (e.g., motor vehicle accidents), particularly in women and those taking higher doses, resulting in significant dose change forms and relabeling for FDA.
Support (If Any): This work was supported, in part, by the VA Advanced Fellowship Program in Mental Health Illness Research and Treatment, VISN 2 Center of Excellence for Suicide Prevention at the Canandaigua VAMC.
Bishop, Todd M.; Lavigne, Jill; Titus, C.; and Pigeon, Wilfred R. (2016). "The Z-Drugs and Their Association with Suicidality, Mortality, and Overdose: A Systematic Review." Journal of Sleep and Sleep Disorders Research 39.Abstract Supplement, A303-A304.
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