Melatonin for Migraine Headache Prophylaxis

Interest in using melatonin for headache disorders has been developing for decades. Over the years, several clues have emerged to suggest that melatonin plays a role in a variety of headache disorders, including migraine, cluster, and tension. In patients with migraine headaches, for instance, some research shows that melatonin levels are lower on days when migraines occur. Patients with chronic migraine also appear to have lower melatonin levels than those with episodic migraine. Nighttime melatonin levels are also lower in patients with migraine compared with those without.

Imaging studies provide additional evidence for melatonin’s role in migraine prevention. During migraine attacks, the hypothalamus is activated. Given the presence of melatonin receptors within the suprachiasmatic nucleus of the hypothalamus, it is conceivable that melatonin’s binding and action in the hypothalamus could play a role in these headaches.

Melatonin might also affect headaches through direct effects on pain and inflammation. Animal studies show that melatonin can reduce pain perception in models of inflammation and neuropathic pain, possibly by binding receptors in the spinal cord or through a variety of other pathways.

Clinical research evaluating melatonin in patients with migraine headaches has focused on migraine prophylaxis. Most studies have found beneficial effects from melatonin on headache frequency; however, some of these studies also have serious methodologic limitations. Several uncontrolled studies found that taking melatonin over a period of 2-6 months significantly reduced migraine headache frequency in both adults and children. In these studies, about 62-78% of patients had a greater than 50% reduction in migraine frequency at the end of the trial compared with at the beginning.

In all clinical trials, melatonin was well tolerated, with sleepiness being the most commonly reported side effect. Less common side effects included fatigue, dizziness, constipation, stomach upset, and dry mouth. In the placebo-controlled trials, side effects were comparable to those of placebo and less common compared with either amitriptyline of sodium valproate.

Melatonin for Migraine Headache Prophylaxis

Interest in using melatonin for headache disorders has been developing for decades. Over the years, several clues have emerged to suggest that melatonin plays a role in a variety of headache disorders, including migraine, cluster, and tension. In patients with migraine headaches, for instance, some research shows that melatonin levels are lower on days when migraines occur. Patients with chronic migraine also appear to have lower melatonin levels than those with episodic migraine. Nighttime melatonin levels are also lower in patients with migraine compared with those without.

Imaging studies provide additional evidence for melatonin’s role in migraine prevention. During migraine attacks, the hypothalamus is activated. Given the presence of melatonin receptors within the suprachiasmatic nucleus of the hypothalamus, it is conceivable that melatonin’s binding and action in the hypothalamus could play a role in these headaches.

Melatonin might also affect headaches through direct effects on pain and inflammation. Animal studies show that melatonin can reduce pain perception in models of inflammation and neuropathic pain, possibly by binding receptors in the spinal cord or through a variety of other pathways.

Clinical research evaluating melatonin in patients with migraine headaches has focused on migraine prophylaxis. Most studies have found beneficial effects from melatonin on headache frequency; however, some of these studies also have serious methodologic limitations. Several uncontrolled studies found that taking melatonin over a period of 2-6 months significantly reduced migraine headache frequency in both adults and children. In these studies, about 62-78% of patients had a greater than 50% reduction in migraine frequency at the end of the trial compared with at the beginning.

In all clinical trials, melatonin was well tolerated, with sleepiness being the most commonly reported side effect. Less common side effects included fatigue, dizziness, constipation, stomach upset, and dry mouth. In the placebo-controlled trials, side effects were comparable to those of placebo and less common compared with either amitriptyline of sodium valproate.

Migraines May Worsen as Menopause Approaches

“Changes in female hormones such as estrogen and progesterone that occur during perimenopause might trigger increased headaches during this time,” said study co-author Dr. Richard Lipton. He is director of the Montefiore Headache Center and vice chair of neurology at Albert Einstein College of Medicine in New York City.

The new research included more than 3,600 women who suffered migraines before and during menopause. The risk of high-frequency migraines (10 or more a month) rose 60% during the transitional time into menopause marked by irregular menstrual cycles (perimenopause).

The risk of migraine was highest during the later stage of perimenopause, when women have low levels of estrogen, the study found.

“Women have been telling doctors that their migraine headaches worsen around menopause, and now we have proof they were right,” study author Dr. Vincent Martin, co-director of the Headache and Facial Pain Program at the University of Cincinnati Neuroscience Institute, said in a news release.

There is help for women who have migraines and are approaching menopause, said study co-author Dr. Jelena Pavlovic, an attending physician in neurology at the Montefiore Headache Center and an assistant professor in the neurology department at Albert Einstein College of Medicine.

“Physicians can prescribe hormonal therapies that level out these changes that occur during the perimenopause and menopause time periods. If the patient is in early perimenopause, you can give birth control pills that level things out. If they are in late perimenopause and they start skipping periods, they can be put on estrogen patches,” Pavlovic said.

But hormones may not always be the culprit. Although the number of migraines rose 76% during menopause, some headaches may be the result of medication overuse, which is common in this age group, according to Martin.

“Women, as they get older, develop lots of aches and pains, joints and back pain, and it is possible their overuse of pain medications for headache and other conditions might actually drive an increase in headaches for the menopause group,” he said.