Analgesic Efficacy of Melatonin: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Previous systematic reviews and meta-analyses of randomized controlled trials have reported controversial findings regarding the effects of melatonin on pain reduction. The aim of this study was to evaluate the efficacy of melatonin on pain among adults using a meta-analysis of randomized, double-blind, placebo-controlled trials (RDBPCTs). PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles were searched up to February 2020. Two of the authors independently evaluated eligibility of the studies based on the pre-determined criteria and extracted data. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) for the pain score change were calculated using a random-effects meta-analysis. Out of 463 that met the initial criteria, a total of 30 trials, which involved 1967 participants with 983 in an intervention group and 984 in a control group, were included in the final analysis. In a random-effects meta-analysis, the use of melatonin reduced chronic pain in all the trials (5 studies, SMD -0.65, 95% CI -0.96 to -0.34, I² = 57.2%) and high-quality trials (4 studies, SMD -0.62, 95% CI -1.01 to -0.23, I² = 49.3%). Moreover, the use of melatonin significantly reduced acute postoperative pain (11 studies, SMD -0.82, 95% CI -1.40 to -0.25, I² = 93.0%). However, the subgroup meta-analysis of high-quality RDBPCTs showed no significant association between them (6 studies, SMD -0.21, 95 % CI -0.66 to 0.24, I² = 82.4%). The current study suggests that melatonin might be used in treatment of chronic pain, while there is no sufficient evidence for acute postoperative or procedural pain. Further trials are warranted to confirm its analgesic effect.