Efficacy of Prolonged-Release Melatonin Administration in Elderly Patients With Treatment Resistant Insomnia: A Post-Hoc Analysis

Abstract

Objective: Melatonin, both immediate and prolonged-release formulations, has been explored as an adjunctive treatment for insomnia, with prolonged-release melatonin demonstrating enhanced efficacy compared to its immediate-release counterpart. However, there remains a gap in understanding its effectiveness specifically in individuals with treatment-resistant insomnia, who continue to experience sleep difficulties despite using traditional hypnotic medications. Methods: An 8-week prospective, open-label, observational study was conducted on 115 patients aged 55 years or older with insomnia several years ago. This is a post-hoc analysis, which was performed on 63 out of 115 patients who were already taking hypnotics and still reported symptoms of insomnia. Per protocol (n=40) and last observation carried forward (LOCF) approaches (n=63) were used, assessing changes in sleep indicators after administering 2 mg of prolonged-release melatonin. Psychometric scales including Pittsburgh Sleep Quality Index (PSQI) and WHO-5 Well-Being Index were used for evaluation at baseline, week 4, and week 8. Results: The per protocol and LOCF analysis revealed substantial improvements in sleep latency, total sleep time, sleep efficiency, and total PSQI scores after 8 weeks of prolonged-release melatonin treatment. The LOCF analysis also revealed WHO-5 Well-Being Index significantly increased. Compared to prolonged-release melatonin monotherapy group with combination therapy group (adding prolonged-release melatonin to previous hypnotics) at baseline, 4 weeks, and 8 weeks after treatment, most variables did not differ between two groups in the per protocol and LOCF analysis. However, only WHO-5 Well-Being Index was higher in monotherapy group than in combination group at 4 weeks and 8 weeks after prolonged-release melatonin treatment in the per protocol analysis. Conclusion: Prolonged-release melatonin demonstrated notable efficacy in ameliorating sleep latency, duration, efficiency, and overall quality in treatment-resistant insomnia patients. The study highlights its potential as a treatment avenue for this challenging cohort, prompting further exploration into its benefits, particularly in improving overall well-being, and advocating for expanded research in this domain. © 2023 Korean Academy of Sleep Medicine.