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Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature review



Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities, and health status. It is frequently treated with benzodiazepines or Z-drugs. Due to adverse events, an increased use of alternative sedative medications has been observed in older adults. We aimed to study the efficacy and safety of alternative sedative medications for treating insomnia in older people, excluding benzodiazepines and Z-drugs.


We conducted a systematic search of MEDLINE (PubMed), EMBASE, and the Cochrane Central register of Controlled Trials databases. We included randomized controlled trials and prospective and retrospective quasi-experimental studies, conducted in patients older than 65 years, without psychiatric or neurological comorbidities.


The systematic search yielded 9483 articles, of which 24 were included in this review, describing nine different sleep medications in total. No clear beneficial impact on sleep could be demonstrated in studies investigating the impact of melatonin (n = 10), paroxetine (n = 1), diphenhydramine (n = 1), tiagabine (n = 2), and valerian (n = 1). Ramelteon slightly improved sleep latency (n = 4), while doxepin was found to provide a sustained sleep improvement with a safety profile that was comparable to placebo (n = 3). Suvorexant showed an improved sleep maintenance with only mild side effects (n = 1). One study detected increased adverse effects of trazodone after 3 months but did not evaluate the effect on sleep.


The overall level of evidence was limited, making it difficult to draw robust conclusions. Preliminary evidence points towards suvorexant, doxepin, and possibly ramelteon as effective and safe pharmacological alternatives for treating insomnia in older adults.

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The authors wish to thank Magdalena Jans of the Medical Library for her help with the design of our search strings.

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All the authors have made substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data. All were involved with drafting the work or revising it critically for important intellectual content and have given final approval of the version published.

Correspondence to Jos Tournoy.

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Judith Sys and Simon Van Cleynenbreugel shared first authorship

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Sys, J., Van Cleynenbreugel, S., Deschodt, M. et al. Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature review. Eur J Clin Pharmacol 76, 363–381 (2020).

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  • Insomnia
  • Older adults
  • Aged
  • Hypnotics and sedatives
  • Antidepressant
  • Sleep