The Therapeutic Effect of Exogenous Melatonin on Depressive Symptoms: A Systematic Review and Meta-Analysis.

Background: Depression-related mortality and morbidity pose growing public health burdens worldwide. Although the therapeutic effect of exogenous melatonin on depression has been investigated, findings remain inconsistent. We conducted this systematic review and meta-analysis to clarify the effectiveness of melatonin in the treatment of depression, including primary and secondary depression symptoms. Methods: We searched the online databases of PubMed, EMBASE, and the Cochrane Library for original studies published up to May 2021. We used STATA 14.0 software to synthesize the results of included studies. To evaluate the effectiveness of melatonin, we calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs) of depression scores between the melatonin and placebo groups. Results: Our literature search returned 754 publications, among which 19 studies with 1,178 patients (715 women, 463 men; mean age: 56.77 years) met inclusion criteria. Melatonin dosages ranged from 2 to 25 mg per day; treatment durations were between 10 days and 3.5 years. Our synthesized results showed that melatonin was not found significantly beneficial for alleviating depressive symptoms (SMD = -0.17, 95% CI = [-0.38, 0.05]). Subgroup analysis demonstrated that the decrease in depression scores measured with the Beck Depression Inventory (BDI) was significant (SMD = -0.52, 95% CI = [-0.73, -0.31]). Conclusions: There is very limited evidence for effects of melatonin on depression.