Melatonin as a Chronobiotic Intervention for Advancing Sleep Timing and Enhancing Sleep Quality in Delayed Sleep-Wake Phase Disorder: A Systematic Review and Meta-Analysis on Randomized Controlled Trials Studies

Background and Objective Delayed Sleep-Wake Phase Disorder (DSWPD) is a sleep disorder that causes difficulty falling asleep, leading to functional impairment in daily activities. This review study analyzes the effectiveness of exogenous melatonin through the optimal timing of melatonin administration and standard dosage on improving sleep quality and shifting the sleep chronobiology of DSWPD patients.Methods Based on the guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020, literature review searches were conducted using databases such as PubMed, Scopus, Web of Science, and Proquest. Methodological quality assessment was performed using Cochrane Risk of Bias 2.0 and the overall analysis was conducted using R 5.4.2 to process the data.Results Overall analysis of actigraphy shows that exogenous melatonin improves sleep quality, such as wakefulness after sleep onset and sleep onset latency (SOL) (z=-4.94, p<0.0001), total sleep time (TST) and time in bed (TIB) (z=3.72, p=0.0002), and shifts sleep timing (z=-8.80, p<0.0001) such as dim light melatonin onset (DLMO), sleep onset time, sleep offset time, and wake-up time. Subgroup analysis indicated that high-dose exogenous melatonin (≥3 mg) reduced SOL parameters (z=-4.11, p<0.0001), while low-dose exogenous melatonin (<3 mg) significantly increased TST parameters (z=6.52, p<0.0001). Meta-regression on melatonin administration 3–5 hours before DLMO was found to be effective (SOL parameter result β=74.6, p=0.005, and TST parameter result β=-49.60, p=0.042).Conclusions As a chronobiotic substance, exogenous melatonin can improve sleep quality and shift the sleep time of DSWPD patients by considering the dosage and timing of administration.