Melatonin Decreases Migraine Frequency and Intensity

Laurie Barclay, MD

September 09, 2004

Sept. 9, 2004 — In chronic migraine sufferers, melatonin decreases headache frequency and intensity and reduces triptan consumption, according to the results of an open-label trial published in the Aug. 24 issue of Neurology.

"There is increasing evidence that melatonin secretion and pineal function are related to headache disorders," write M. F. P. Peres, MD PhD, from the Hospital Israelita Albert Einstein in São Paulo, Brazil, and colleagues. "Altered melatonin levels have been found in cluster headache, migraine with and without aura, menstrual migraine, and chronic migraine."

Of 40 patients with episodic migraine with or without aura meeting International Headache Society (IHS) diagnostic criteria who were screened during the baseline period, three patients did not have headaches during the baseline period, and three patients were lost to follow-up evaluation. Patients with chronic daily headache, insomnia, or considerable sleep hygiene problems were excluded, as were patients receiving preventive therapy three months before recruitment for the trial. Study participants averaged between two and eight migraine headaches per month.

Of 34 patients (29 women, five men) who started prophylactic treatment with melatonin (3 mg, 30 minutes before bedtime) 32 patients completed the four-month study, consisting of a one-month baseline period and a three-month therapy phase. During the study, participants completed a study diary, and they continued to take triptans, ergots, nonsteroidal anti-inflammatory drugs, and analgesics as needed.

Of 32 patients who completed the study, 25 patients (78.1%) had at least a 50% reduction in headache frequency from baseline, eight patients (25%) had no headaches, and none of the patients had increased headaches after three months of therapy. Reduction in frequency was greater than 75% in seven patients (21.8%), and 50% to 75% in 10 patients (31.3%).

Melatonin decreased mean headache frequency per month from 7.6 ± 3.2 at baseline to 4.4 ± 2.5 headaches at month one, and to 3.0 ± 3.1 headaches at month three ( P < .001). On a 0-to-10 scale, mean headache intensity decreased from 7.4 ± 1.3 at baseline to 5.5 ± 1.9 at month one, and to 3.6 ± 2.7 at month three ( P < .001). Mean headache duration in hours decreased from 19.8 ± 19.8 at baseline, to 10.2 ± 13.4 at month one, and to 8.8 ± 12.4 at month three ( P < .001).

Patients reported significant clinical improvement by month one. Other benefits were decreases in overall analgesic and triptan consumption ( P < .001) and in menstrually associated migraine. Three patients spontaneously reported increase in libido. Of two patients who withdrew from the study, one had excessive sleepiness and the other had alopecia. There were no significant changes in body weight.

"This is the first study to assess melatonin efficacy in migraine prevention," the authors write. "In our small series of migraine patients, melatonin was effective in reducing the number of headache days per month. A controlled study may be worthwhile."

Neurology. 2004;63:757

Reviewed by Gary D. Vogin, MD

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