Safety and Efficacy of Melatonin for Sleep Disorders in Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Abstract

Introduction/objective: Sleep disruption is common among patients with malignancy and may worsen quality of life, treatment tolerance, and symptom burden. Melatonin is a circadianregulating hormone with a favorable safety profile and potential sleep-promoting effects. This metaanalysis and systematic review evaluated the safety and efficacy of melatonin for sleep-related outcomes in patients with cancer.

Methods: Scopus, PubMed, Web of Science, ScienceDirect, Cochrane Library, ClinicalTrials.gov, and EMBASE were systematically searched from inception to 1 June 2026 without language or country restrictions. Randomized clinical trials comparing melatonin with placebo or an active control in patients with cancer and reporting sleep-related outcomes were eligible. Data extraction, study selection, and riskof- bias assessment using the Joanna Briggs Institute checklist were performed by two reviewers independently. Random-effects meta-analyses with Hartung-Knapp adjustment were conducted in Stata 17.0.

Results: Data from seven studies were pooled in the meta-analysis, and thirteen articles were included in the systematic review. The overall effect of melatonin was insignificant (SMD = -0.85 with a 95% CI of -2.46 to 0.76) with high heterogeneity among studies (I2 = 94.5%). Subgroup analysis revealed a significant decrease in the Pittsburgh Sleep Quality Index (PSQI) in US studies (SMD = -0.57, 95% CI: [-0.99, -0.14], I2 = 31.5%). Meta-analysis of the seven PSQI components showed no significant item-level improvement with melatonin treatment. Studies using non-PSQI sleep outcomes showed mixed findings, with short-term improvement in insomnia severity in one trial but modest or non-significant effects in others.

Discussion: While the overall impact of melatonin on sleep quality was not statistically significant, subgroup analyses and qualitative evidence indicate clinically relevant benefits.

Conclusion: Melatonin shows promising but uncertain benefits for sleep disruptions in patients with malignancies. However, the evidence should be interpreted cautiously because of substantial clinical and statistical heterogeneity, limited sample sizes, short intervention durations, and predominantly subjective sleep measures. Larger, well-standardized randomized trials using both subjective and objective sleep assessments are needed.