Study Examines Melatonin to Treat Pain in Pediatric Headache

A pilot, randomized study recently examined the use of melatonin to treat pediatric acute migraine pain, but the trial was marked by high drop out rates and appeared to have limited usefulness for daytime attacks.

The authors of the study, published in Headache, said the aim of the study was to determine whether a high or low dose of melatonin would be more effective for treating acute migraine in children or adolescents.

Melatonin is effective for migraine prevention in adults, they said, and has been used for pain in children undergoing procedures. Besides inflicting pain, migraine can affect children’s quality of life, including academic performance and emotional well-being.

While evidence-based prescription drugs for acute migraine pain are available for children, not all are appropriate, may have side effects, and some parents may wish to try something they consider natural, the authors said.

The melatonin used was a commercially available supplement flavored with chocolate and the participants were recruited from a pediatric headache program at the University of California San Francisco (UCSF).

The goal of the study was to see if a “high” or “low” dose of melatonin would relieve migraine pain in children, 5% of whom are affected by age 10, with increasing prevalence during adolescence.

The open-label, single-center, dose-finding trial enrolled children and adolescents aged 4-17 years with episodic migraine.

Drawing from a study examining pain scores of children treated in an emergency department, the authors considered a change of ≥3 cm on the pain scale to be clinically significant; they aimed to detect a mean difference of 3 cm (SD3) between melatonin doses.

Participants kept a headache diary and were told to treat only those attacks that were preceded by at least 24 hours of headache freedom.

Doses of melatonin were randomized to higher or lower doses: for children under 40 kilograms, 4 mg vs 1 mg; for those 40 kilograms or over, 8 mg vs 2 mg.

The primary outcome measure was change in mean pain score between time 0 and 2 hours. Secondary outcomes included 2-hour pain-relief and pain-freedom rates.

The study enrolled 84 children, with 42 in each group; they had a mean (SD) age of11.8 (3.5) years and 55% (46/84) were female.

The mean number (SD) of headache days per month was 5.6 (3.8). Sixty-six (79%) participants provided outcome data and were included in the analyses, 24 in the high-dose group and 22 in the low-dose group.

Forty-three percent of the patients dropped out rate using the higher dose (18/42) compared with 48% (20/42) taking the lower dose.

The mean (SD) change in pain intensity at 2 hours was −2.7 (2.1) cm in the high-dose group vs −2.3 (2.1) cm in the low-dose group (P = .581), a difference of 0.4 cm (95% CI, 1.17-1.92).

Neither dose tested hit the primary outcome measure of decreasing mean pain intensity by at least 3 cm at 2 hours, and both groups had a high drop-out rate.

Two-hour pain-freedom rate was 41% (7/17) vs. 27% (4/15) in the high-dose vs. low-dose groups (P = .415), and 2-hour pain-relief rate was 94% (16/17) vs 80% (12/15), (P = .482).

In addition, napping was seen more often at the higher dose than the lower dose, 67% (14/21) vs 47% (9/19), respectively.

However, the higher mg/kg dose of melatonin and napping were each independently associated with greater headache benefit.

Controlling for napping, for every 0.1 mg/kg increase in melatonin dose, pain scores decreased by 0.7 cm at 2 hours, 1.3 cm at 4 hours, and 3.6 cm at 24 hours.

The proportion who were pain-free at 2 hours was numerically higher in the higher dose, but not statistically significant.

There were no serious adverse events.

Researchers had hoped to use this study as the basis for a future placebo-controlled efficacy trial. But the consequence of napping could limit melatonin’s usefulness to only evening attacks.

Reference

Gelfand AA, Ross AC, Irwin SL, Greene KA, Qubty WF, Allen IE. Melatonin for acute treatment of migraine in children and adolescents: A pilot randomized trial. Headache. 2020 Sep;60(8):1712-1721. doi: 10.1111/head.13934.