Therapeutic Role of Melatonin in Pediatric Migraine: A Systematic Review and Meta-Analysis

OBJECTIVES:

The objective of the current study is to compare the efficacy and safety of melatonin in pediatric migraine.

METHODS:

Medline^® and Embase^® databases were searched via Ovid with English language restriction. In addition, references of included studies and clinicaltrials.gov were manually searched for relevant studies. Inclusion criteria were observational and randomized controlled trials (RCTs) in children with migraine, treated with melatonin. The Newcastle-Ottawa Scale and Cochrane risk of bias V 2.0 (ROB 2) were used to assess study quality of observational and RCTs, respectively. A meta-analysis using fixed effects model was conducted to calculate pooled effect estimates with 95% confidence intervals (CI) for good response (>50% decrease in monthly headache frequency during the follow-up period), monthly headache frequency, severity, and duration of headache.

RESULTS:

Out of the 60 articles screened, 5 publications (4 studies, N=224) were included for systematic review. One retrospective (N=32) and 1 open label single arm trial (N=22) showed that headache attacks had decreased by more than 50% with melatonin use. Two RCTs (N=170) comparing melatonin with amitriptyline were included for meta-analyses. Pooled analyses showed that amitryptiline showed better response (risk ratio [RR] 1.31; 95% CI 1.10 to 1.56) and better efficacy compared to melatonin in reducing monthly headache frequency (mean difference [MD] -2.71, 95% CI -3.95 to -1.48), severity of headache (MD -1.97, 95% CI -2.31 to -1.62), and duration of headache (MD -0.88, 95% CI -1.12 to -0.63).

CONCLUSIONS:

Melatonin might be considered an effective drug and without life-threatening side effects in prophylaxis of migraine in children. Melatonin and amitriptyline both are effective and safe, but amitriptyline can be considered as a more effective drug. Further high-quality RCTs and systematic reviews are required for conclusive determination of its effectiveness and tolerability compared to active comparators.