Efficacy and Safety of Melatonin as Prophylaxis for Migraine in Adults: A Meta-analysis

Abstract

Aims: To evaluate the efficacy and safety of melatonin for migraine prophylaxis in adults.

Methods: After a comprehensive literature search in the MEDLINE, Cochrane Database, and International Clinical Trial Registry Platform databases, reviewers extracted data from three relevant articles. PRISMA guidelines were followed in the selection, analysis, and reporting of the findings. Quality assessment was performed using the Cochrane risk of bias assessment tool. A random-effects model was used to estimate the effect size, and meta-regression was performed for variables with a likely influence on effect size. Subgroup analysis was performed based on the comparison used in the included studies.

Results: Melatonin therapy in migraine was associated with a significantly higher responder rate when compared to both placebo and standard therapy (OR = 1.84; 95% CI: 1.08 to 3.14; P = .03). The results of the meta-analyses indicated that melatonin can achieve a significant reduction in frequency of migraine attacks (MD = 1.00; 95% CI: 0.02 to 1.98; P = .04), migraine attack duration (MD = 5.02; 95% CI: 0. 91 to 9.13; P = .02), use of analgesics (MD = 1.43; 95% CI: 0.38 to 2.48; P = .008), and migraine severity (MD = 1.93; 95% CI: 1.23 to 2.63; P < .0001) over placebo, but had no significant effects in comparison to amitriptyline or valproate. There was no significant difference in the occurrence of common adverse drug reactions, such as drowsiness and fatigue, between the melatonin group and the comparison groups.

Conclusions: Melatonin showed a beneficial prophylactic role in migraine, with a better responder rate in comparison to placebo in reducing migraine severity, mean attack duration, mean attack frequency, and analgesic use, but did not show significant effects in comparison to amitriptyline or valproate.

Fig 1

PRISMA flowchart showing the study selection process.

Fig 2

Forest plot of included studies assessing responder rate between melatonin and placebo/standard therapy. Mantel-Haenszel, random-effects model. (1) = melatonin vs amitriptyline; (2) melatonin vs valproic acid.

Fig 3

Forest plot of included studies assessing change in mean migraine severity. Inverse variance, random-effects model. (1) = melatonin vs amitriptyline; (2) melatonin vs valproic acid.

Fig 4

Forest plot of included studies assessing change in mean migraine attack duration. Inverse variance, random-effects model. (1) = melatonin vs amitriptyline; (2) melatonin vs valproic acid.

Fig 5

Forest plot of included studies assessing change in mean migraine attack frequency. Inverse variance, random-effects model. (1) = melatonin vs amitriptyline; (2) melatonin vs valproic acid.

Fig 6

Forest plot of included studies assessing mean decrease in analgesic medications. Inverse variance, random-effects model. (1) = melatonin vs amitriptyline; (2) melatonin vs valproic acid.

Fig 7

Forest plot of included studies for assessing ADRs (drowsiness and fatigue). Mantel-Haenszel, random-effects model. (1) = melatonin vs amitriptyline; (2) melatonin vs valproic acid.

Appendix 1

L’Abbé plot depicting the effectiveness of melatonin over control treatments (placebo/standard therapy) on responder rate in adult migraineurs. The solid line represents the line of no effect. The dotted line represents the combined effect of all the studies as OR. The circle represents individual studies and size variations as a function of weight.

Appendix 2

Bubble plot showing the effect of duration of therapy on the OR for responder rate across studies. Individual studies are depicted by circles along the line of meta-regression.