Comparative efficacy and safety of different pharmacological interventions for the treatment of depression associated with insomnia in the elderly population: a systematic review and network meta-analysis

This study aimed to compare the efficacy and safety of different active agent treatments for depression associated with sleep disorders in the elderly population. The major international databases, including Medline (via PubMed), Cochrane Library, Scopus and Embase, WHO International Clinical Trials Registry Platform, ClinicalTrials, were searched using a predesigned search strategy. Randomised controlled trials (RCTs) that had compared the pharmacological treatments or placebo therapy interventions were included. The mean difference with a 95% confidence interval was used to summarise the effect size in the network meta-analysis. The frequentist approach was used for data analysis. In total, 12 RCTs out of 8673 retrieved references met the inclusion criteria in this review (3070 participants). All types of intervention were effective in decreased Insomnia Severity Index (ISI) and depression score, and sertraline had the highest probability of being the most effective intervention in decreasing the ISI (standard mean difference (SMD) = -2.17, 95% confidence interval (95% CI): -2.60, -1.75), Hamilton Depression Scale (HAM-D: SMD = -3.10, 95% CI: -3.60, -2.61) in elderly patients with depression and insomnia. Safety assessments included treatment-emergent adverse events and serious adverse events. In terms of the number of patients reporting escitalopram and zuranolone, zolpidem, seltorexant and eszopiclone had higher risks of serious adverse events than placebo or other treatments. In conclusion, sertraline had the highest probability of being the optimal intervention for decreased ISI and HAM-D in elderly patients with depressive and insomnia. Escitalopram, zuranolone, and seltorexant did not show overall material benefits in reducing ISI. These results should serve evidence-based clinical practice.