Effects of melatonin on postoperative sleep quality: a systematic review, meta-analysis, and trial sequential analysis

Purpose Postoperative sleep disturbances are common. Although several studies have examined the effect of melatonin on postoperative sleep disturbances, the results have not reached any definitive conclusion. We sought to conduct a systematic review to compare the effects of melatonin and melatonin agonists on postoperative sleep quality with those of placebo or no treatment in adult patients who underwent surgery under general or regional anesthesia. Methods We searched MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Web of Science, ClinicalTrials.gov, and the UMIN Clinical Trials Registry up to 18 April 2022. Randomized clinical trials examining the effects of melatonin or melatonin agonists in patients undergoing general or regional anesthesia with sedation for any surgery were eligible for inclusion. The primary outcome was sleep quality measured using a visual analog scale (VAS). The secondary outcomes were postoperative sleep duration, sleepiness, pain, opioid consumption, quality of recovery, and adverse events. A random-effects model was used to combine the results. We assessed study quality with the Cochrane Risk of Bias Tool version 2. We applied a trial sequential analysis to assess the precision of the combined results. Results Eight studies (516 participants) were analyzed for sleep quality. Of those, four studies used only a short duration of melatonin, either on the night before and the day of surgery or only on the day of surgery. A random-effects meta-analysis showed that melatonin did not improve sleep quality measured by VAS compared with placebo (mean difference, -0.75 mm; 95% confidence interval, -4.86 to 3.35), with low heterogeneity (I 2 , 5%). Trial sequential analysis revealed that the accrued information size ( n = 516) reached the estimated required information size ( n = 295). We downgraded the certainty of the evidence because of the high risk of bias. The effect on postoperative adverse events was comparable between the melatonin and control groups. Conclusion Our results indicate that melatonin supplementation does not improve postoperative sleep quality measured with the VAS compared with placebo in adult patients (GRADE: moderate). Study registration PROSPERO (CRD42020180167); registered 27 October 2022.