This study evaluates the efficacy of melatonin compared to placebo and other drugs in reducing the frequency of migraine episodes and secondary outcomes through the analysis of previous trials.

Migraine is one of the most common neurological diseases, presenting different characteristics among patients. Therefore, there is a need to identify preventive medications that offer more efficacy and fewer adverse effects. Melatonin is a promising therapeutic alternative in this context due to its analgesic, neuromodulatory, and cerebral blood flow regulatory mechanism.

Cochrane, Embase, and PubMed databases were searched to select relevant studies based on specific inclusion criteria. Data extraction and statistical analysis were performed using R studio (version 4.3.1), ensuring model heterogeneity. The Confidence in Network Meta-Analysis (CINeMA) tool was used to interpret results, accounting for potential biases and limitations.

Nine studies with 783 patients were included. Seven treatment strategies were compared. The network meta-analysis revealed no statistically significant differences in Monthly Headache Frequency between Melatonin and Amitriptyline (SD: −1.8; 95% CrI [−5.2, 1.0]), Naproxen (SD: −0.98; 95% CrI [−5.5, 3.8]), Valproic Acid (SD: −0.60; 95% CrI [−5.0, 3.6]), Topiramate (SD: 0.081; 95% CrI [−5.0, 4.7]), Propranolol (SD: 1.4; 95% CrI [−3.7, 6.6]), and Placebo (SD: 0.49; 95% CrI [−1.6, 2.7]). Other outcomes, including MIDAS scores, analgesic use, and headache duration, showed no significant differences among treatment arms.

This systematic review and network meta-analysis found no strong evidence supporting the efficacy of melatonin in treating episodic migraine. Further research is needed to explore melatonin’s role in migraine pathophysiology and its potential benefits for patients unresponsive to conventional treatments.