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Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial.

Frontiers in nutrition
May 5, 2025
Vincenzo Piccolo et al. (6 authors)
Journal ArticleHuman Study
Study Details

Study Goal

The researchers aimed to assess the efficacy of hydrodispersible palmitoylethanolamide (PEA) combined with melatonin in reducing migraine frequency, intensity, duration, and disability.

Results Summary

The study found that the PEA-melatonin combination significantly reduced migraine frequency, duration, intensity, and disability after three months of treatment, with no reported adverse effects. A notable mitigation of migraine-related symptoms was also observed.

Population

60 migraine patients (30 in treatment group, 30 in placebo group) recruited by the I.N.B.B. Consortium in Italy.

Effective Dosage

1,200 mg PEA and 0.2 mg melatonin.

Duration

3 months.

Interactions

None mentioned.

Extracted Claims (7)
InterventionDirectionEndpointPopulationDosageImpactClaim #
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
decrease
frequency of migraine attacks
patients with migraine
from 3.4 ± 0.5 MMDs to 2.2 ± 0.4 MMDs
displayed a significant reduction
#1
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
decrease
duration of migraine attacks
patients with migraine
-
displayed a reduction
#2
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
decrease
intensity of migraine attacks
patients with migraine
-
displayed a reduction
#3
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
decrease
grade of disability from migraine attacks
patients with migraine
-
displayed a reduction
#4
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
decrease
incidence of associated symptoms of migraine attacks
patients with migraine
-
displayed a reduction
#5
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
decrease
migraine-related symptomatology
patients with migraine
-
observed a significant mitigation
#6
hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) (PEATONIDE®)
no change
adverse effects
patients with migraine
-
No adverse effects were observed
#7
Abstract

INTRODUCTION: Migraines are neurological disorders which significantly impact quality of life. Current pharmacological treatments often have adverse effects, prompting the search for alternatives with fewer side effects. Several studies have described the antimigraine properties of palmitoylethanolamide (PEA) and melatonin. MATERIALS AND METHODS: Our research assessed the efficacy of the association of hydrodispersible PEA (1,200 mg) and melatonin (0.2 mg) by a randomized, three-month, double-blind, placebo-controlled trial (PEATONIDE®; n = 30 patients; placebo; n = 30 patients). The participants were recruited by "I.N.B.B. Consortium" in Italy. The primary outcome was the reduction of migraine frequency, while secondary outcomes included the reduction of intensity, duration, and grade of disability. The parameters were assessed by a self-reported daily headache diary. RESULTS: The formulation displayed a significant reduction in frequency (T3 months: 2.2 ± 0.4 MMDs; T0 baseline: 3.4 ± 0.5 MMDs, ***p < 0.001 vs baseline T0) and duration, intensity, disability, and incidence of associated symptoms of migraine attacks after 3 months of treatment. No adverse effects were observed during the treatment. In addition, a significant mitigation of migraine-related symptomatology was observed. CONCLUSION: These findings suggest that PEATONIDE® may be a promising adjunctive approach for migraine management. However, given the relatively small sample size, further large-scale and multicenter trials are needed to confirm its clinical applicability in broader migraine population.

Study Links
Quality Scores
Safety100
Efficacy85/10
Quality75/10
Research Impact Scores
APT Score0.05
Weight Score1.25
Normalized Score0.89
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