Efficacy and Safety of Sustained-Release Melatonin Capsules (2 mg) in Healthy Adults with Poor Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Trial

Sleep disturbances and poor sleep quality are growing public health concerns, adversely affecting both physical and mental health. While exogenous melatonin supplements are used to manage the condition, there is limited evidence available on the efficacy of sustained-release (SR) melatonin formulations. This multicenter, randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of melatonin-SR capsules (2 mg) in healthy adults with poor sleep quality. Participants aged 30–60 years with poor sleep quality received melatonin-SR (2 mg) or a placebo capsule at night for 28 days. Changes from baseline to day 28 in polysomnography (PSG)-derived sleep parameters, Pittsburgh Sleep Quality Index (PSQI), WHO-5 Well-Being Index, sleep diary parameters, and safety profile were evaluated. Of 62 enrolled participants, 59 (melatonin-SR, n = 28; placebo, n = 31) completed the study. Compared with placebo, melatonin-SR supplementation resulted in significant improvements at day 28 in PSG-derived sleep efficiency (change from baseline: 3.49 for melatonin-SR vs. −6.30% for placebo; p = 0.001) and total sleep time (change from baseline: 23.83 for melatonin-SR vs. −39.25 min for placebo; p = 0.001), along with significant reductions in sleep onset latency (change from baseline: −10.28 for melatonin-SR vs. 16.70 min for placebo; p = 0.031) and wake after sleep onset (change from baseline: −14.92 for melatonin-SR vs. 24.71 min for placebo; p = 0.001). Melatonin-SR supplementation demonstrated a large treatment effect for the improvement in sleep efficiency compared with placebo (Cohen’s d = 0.9). A significant reduction in PSQI global scores was observed in the melatonin-SR group from day 07 onwards (change from baseline on day 07: −2.21 vs. −0.23; day 14: −4.86 vs. −0.65; and day 28: −5.61 vs. −0.65 for melatonin-SR and placebo, respectively; p = 0.001). Improvement in subjective psychological well-being was significant from day 14 onwards (change from baseline on day 14: 9.86 vs. 0.77; and day 28: 13.29 vs. 0.77 for melatonin-SR and placebo, respectively; p = 0.001). A significant improvement in subjective sleep parameters at day 28 (p < 0.05) was observed. Reported adverse events in both groups were mild and transient in nature. Supplementation with melatonin-SR 2 mg capsule at night for 28 days was found to be effective and safe in improving objective and subjective sleep quality outcomes and overall well-being in the trial population.