Efficacy and safety of Z-substances in the management of insomnia in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing

Abstract

Abstract Background Z-drugs are usually prescribed as first line pharmacological therapy for insomnia. However, the benefits and risks of Z-drugs may differ for older adults. This systematic review investigated the available evidence on the efficacy and safety of Z-drugs in the management of insomnia in older adults. Methods The Cochrane database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE and EMBASE were searched for systematic reviews, meta-analyses, controlled interventional and observational studies using a pre-formulated search term. The target population was older adults (≥65 years old) with insomnia. Studies were included if they reported efficacy and/or safety outcomes of the use of Z-drugs for the management of insomnia compared to placebo, usual or no treatment, or other pharmacological agents. Results Eighteen studies were included (8 interventional and 10 observational studies). In short-term interventional studies, Z-drugs were similarly or better efficacious in improving both sleep and daytime parameters than placebo or other pharmacological treatments, while showing good results on measures of safety. However, in longer-term observational studies, Z-drugs significantly increased the risk for falls and fractures in comparison to no treatment or melatonin agonists. Conclusions Analyzing the evidence from short-term interventional studies, Z-drugs appear effective and safe for treatment of insomnia in older adults, but they may have unfavorable side effects when used for longer periods of time. We, therefore, recommend discontinuing Z-drugs, principally because of the high risk for falls and fractures. Nonetheless, quality and quantity of evidence are low. Due to the scarcity of data, especially concerning drug dependence after longer periods of treatment and due to the significantly increased risk for falls and fractures, further studies are needed to evaluate the benefit-risk profile of Z-drugs use in older patients, particularly for long-term use.