Effect of age on hypnotics' efficacy and safety in insomnia: A systematic review and meta-analysis

Objective: This systematic review and meta-analysis evaluates the efficacy in improving sleep quality and safety of hypnotics in individuals aged 65 years or older compared to those under 65 years.

Methods: MEDLINE, EMBASE, Web of Science, and EBM Reviews were searched for randomized clinical trials comparing hypnotics to the placebo in adults with chronic insomnia between Jan 2000 and Dec 2022. The efficacy outcome included all participant self-assessments sleep quality questionnaires. The safety outcome included acceptability and tolerance. Standardized mean differences (SMD) was estimated using a random effect model.

Results: We included 17 and 53 clinical trials with 3688 and 14,720 participants in the ≥65 years and <65 years group respectively. The SMD for the sleep quality outcome was -0.36 [Confidence interval (CI) 95 %: 0.45;-0.26] in the ≥65 years group compared to -0.51 [95%CI: 0.61; -0.41] in the <65 years group (p = 0.02). Differences in efficacy were observed between pharmacological classes. The overall SMD for the tolerance outcome was - 0.25 [95%CI: 0.34; -0.16] favoring the placebo group (p < 0.001). In the ≥65 years group the SMD was -0.07 [95%CI: 0.21; 0.08] compared to -0.31 [95%CI: 0.41; -0.21] in the <65 years group (p = 0.01). There were no differences for acceptability.

Conclusion: We found that some hypnotics classes could be less effective in older individuals. We encourage authors to include details on multimorbidity and polypharmacy in their publications.