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Use of melatonin versus valproic acid in prophylaxis of migraine patients: A double-blind randomized clinical trial.

Restorative neurology and neuroscience
January 1, 2017
Mohsen Ebrahimi-Monfared et al. (5 authors)
Comparative StudyJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tHuman StudyClinical
Study Details

Study Goal

The researchers aimed to compare the therapeutic effect of melatonin versus sodium valproate in the prophylaxis of chronic migraine.

Results Summary

Melatonin significantly reduced migraine attack frequency, duration, severity, and MIDAS scores, with efficacy comparable to sodium valproate but with fewer adverse events. The placebo group showed no significant improvements.

Population

Patients with chronic migraine receiving baseline therapy with nortriptyline and propranolol.

Effective Dosage

3 mg melatonin daily.

Duration

2 months.

Interactions

None mentioned.

Extracted Claims (18)
InterventionDirectionEndpointPopulationDosageImpactClaim #
3 mg melatonin
decrease
mean of monthly attack frequency
patients with chronic migraine
baseline: 4.2, I: 3.1, II: 2.5
significantly reduced
#1
200 mg sodium valproate
decrease
mean of monthly attack frequency
patients with chronic migraine
baseline: 4.3, I: 3.1, II: 2.3
significantly reduced
#2
placebo
no change
mean of monthly attack frequency
patients with chronic migraine
baseline: 4.1, I: 3.8, II: 3.8
not significantly reduced
#3
3 mg melatonin
decrease
attack duration (hr)
patients with chronic migraine
baseline: 19.8, I: 10.1, II: 8.7
significantly reduced
#4
200 mg sodium valproate
decrease
attack duration (hr)
patients with chronic migraine
baseline: 19.5, I: 10.2, II: 8.8
significantly reduced
#5
placebo
no change
attack duration (hr)
patients with chronic migraine
baseline: 19.6, I: 15.4, II: 14.1
not significantly reduced
#6
3 mg melatonin
decrease
attack severity
patients with chronic migraine
baseline: 7.3, I: 5.4, II: 3.5
significantly reduced
#7
200 mg sodium valproate
decrease
attack severity
patients with chronic migraine
baseline: 7.4, I: 5.3, II: 3.4
significantly reduced
#8
placebo
no change
attack severity
patients with chronic migraine
baseline: 7.3, I: 6.4, II: 6
not significantly reduced
#9
3 mg melatonin
decrease
MIDAS score
patients with chronic migraine
baseline: 15.2, II: 8.9
significantly reduced
#10
200 mg sodium valproate
decrease
MIDAS score
patients with chronic migraine
baseline: 16.1, II: 8.3
significantly reduced
#11
placebo
no change
MIDAS score
patients with chronic migraine
baseline: 16, II: 12.1
not significantly reduced
#12
3 mg melatonin
increase
adverse events
patients with chronic migraine
2 (5.71%)
had adverse events
#13
200 mg sodium valproate
increase
adverse events
patients with chronic migraine
8 (22.85%)
had adverse events
#14
placebo
increase
adverse events
patients with chronic migraine
1 (2.85%)
had adverse events
#15
adjuvant treatment with melatonin
increase
clinical efficacy
patients with chronic migraine
-
was found to be superior to the placebo
#16
adjuvant treatment with melatonin
no change
clinical efficacy
patients with chronic migraine
-
had the same clinical efficacy as sodium valproate
#17
adjuvant treatment with melatonin
increase
tolerability
patients with chronic migraine
-
had higher tolerability
#18
Abstract

BACKGROUND: Melatonin is known to be effective in curing migraine. OBJECTIVE: This study aimed to investigate the therapeutic effect of melatonin versus sodium valproate in the prophylaxis of chronic migraine. METHODS: This randomized, double-blind, placebo-controlled clinical trial included patients with chronic migraine who were divided into three equal sized groups, and baseline therapy with nortriptyline (10-25 mg) and propranolol (20-40 mg) was used. Patients in groups A, B, and C were adjunctively treated daily with 3 mg melatonin, 200 mg sodium valproate, and a placebo, respectively. The patients underwent treatment for 2 months and follow-up was done at baseline (baseline), first (I) and second month (II). Attack frequency (AF), attack duration, attack severity, Migraine Disability Assessment (MIDAS) score (within 3 months in two steps), analgesic intake, and drug side effects between the groups and during follow-up were compared. RESULTS: The mean of monthly AF (melatonin: baseline: 4.2, I: 3.1, II: 2.5, p = 0.018; valproate: baseline: 4.3, I: 3.1, II: 2.3, p = 0.001; placebo: baseline: 4.1, I: 3.8, II: 3.8 p = 0.211), attack duration (hr) (melatonin: baseline: 19.8, I: 10.1, II: 8.7, p < 0.001; valproate: baseline: 19.5, I: 10.2, II: 8.8, p < 0.001; placebo: baseline: 19.6, I: 15.4, II: 14.1, p = 0.271), attack severity (melatonin: baseline: 7.3, I: 5.4, II: 3.5, p < 0.001; valproate: baseline: 7.4, I: 5.3, II: 3.4, p = 0.000; placebo: baseline: 7.3, I: 6.4, II: 6, p = 0.321), and MIDAS score (melatonin: baseline: 15.2, II: 8.9, p = 0.005; valproate: baseline: 16.1, II: 8.3, p = 0.001; placebo: baseline: 16, II: 12.1, p = 0.44), were significantly reduced in the melatonin and sodium valproate groups, but not in the placebo groups. Adverse events were reported in 11 patients (10.47%): 2 (5.71%) during melatonin treatment, 8 (22.85%) during valproate, and 1 (2.85%) during placebo. CONCLUSION: The adjuvant treatment with melatonin was found to be superior to the placebo and had the same clinical efficacy as sodium valproate, but with higher tolerability. Melatonin may prove to be an efficient substitute for sodium valproate, as a chronic migraine prophylaxis.

Medical Subject Headings (MeSH)
AdolescentAdultAgedAged, 80 and overAnalgesicsCentral Nervous System AgentsDisability EvaluationDouble-Blind MethodFemaleFollow-Up StudiesHumansMaleMelatoninMiddle AgedMigraine DisordersSeverity of Illness IndexTreatment OutcomeValproic AcidYoung Adult
Study Links
Quality Scores
Safety85
Efficacy90/10
Quality88/10
Citation Metrics
Total Citations41
Citations/Year5.1
Relative Citation Ratio2.42
NIH Percentile79.9%
Research Impact Scores
APT Score0.95
Weight Score2.22
Normalized Score0.88
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