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

IntroductionMigraines 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 palmitoylethanolami...

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Main Authors: Vincenzo Piccolo, Adua Marzocchi, Maria Maisto, Vincenzo Summa, Gian Carlo Tenore, Angela Amoresano
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Nutrition
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Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2025.1560654/full
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author Vincenzo Piccolo
Adua Marzocchi
Maria Maisto
Vincenzo Summa
Gian Carlo Tenore
Angela Amoresano
Angela Amoresano
author_facet Vincenzo Piccolo
Adua Marzocchi
Maria Maisto
Vincenzo Summa
Gian Carlo Tenore
Angela Amoresano
Angela Amoresano
author_sort Vincenzo Piccolo
collection DOAJ
description IntroductionMigraines 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 methodsOur 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.ResultsThe 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.ConclusionThese 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.
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spelling doaj-art-e8dbeaf808334c8ba1a2cb81d8204f7a2025-08-20T02:16:44ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-04-011210.3389/fnut.2025.15606541560654Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trialVincenzo Piccolo0Adua Marzocchi1Maria Maisto2Vincenzo Summa3Gian Carlo Tenore4Angela Amoresano5Angela Amoresano6Department of Pharmacy, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, Naples, ItalyInteruniversity Consortium of Biostructures and Biosystems (INBB), Rome, ItalyDepartment of Chemical Sciences, University of Naples Federico II, Naples, ItalyIntroductionMigraines 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 methodsOur 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.ResultsThe 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fnut.2025.1560654/fullmigrainepalmitoylethanolamidemelatoninsupplementclinical trial
spellingShingle Vincenzo Piccolo
Adua Marzocchi
Maria Maisto
Vincenzo Summa
Gian Carlo Tenore
Angela Amoresano
Angela Amoresano
Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
Frontiers in Nutrition
migraine
palmitoylethanolamide
melatonin
supplement
clinical trial
title Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
title_full Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
title_fullStr Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
title_full_unstemmed Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
title_short Fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine: results from a randomized clinical trial
title_sort fixed combination of palmitoylethanolamide and melatonin in preventive therapy of migraine results from a randomized clinical trial
topic migraine
palmitoylethanolamide
melatonin
supplement
clinical trial
url https://www.frontiersin.org/articles/10.3389/fnut.2025.1560654/full
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