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.
The role of melatonin in migraine headaches could also be
related to its impact on sleep. Melatonin levels are increased at night,
inducing the onset of sleep. Lack of sleep can be a migraine trigger, while
adequate sleep can reduce migraine attacks.
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.
Ebrahimi-Monfared and colleagues compared melatonin with sodium valproate and
placebo in a randomized, double-blind, placebo-controlled trial. In this study,
105 adults with chronic migraine were allocated to receive melatonin 3 mg 30
minutes before bed, sodium valproate 200 mg daily, or placebo for 2 months. All
patients also received nortriptyline 25 mg and propranolol 20 mg daily.
Melatonin and sodium valproate reduced migraine headache frequency and duration
to a similar degree, and each significantly more than placebo (P < .001).
Melatonin reduced migraine attack frequency by about 40% and migraine duration
by about 56% compared with baseline.
Gonçalves and colleagues conducted the most rigorous trial
to date. In this randomized, double-blind, placebo-controlled trial, 196 adults
with migraine headaches occurring two to eight times per month were allocated
to receive melatonin 3 mg, amitriptyline 25 mg, or placebo at bedtime for 12
weeks. Melatonin reduced the number of migraine headache days by 2.7 compared
with 2.2 with amitriptyline (P = .19) and 1.1 with placebo (P = .009). In terms
of responder rate, melatonin was significantly more effective than
amitriptyline. In the melatonin group, 54.4% of patients had a > 50%
reduction in migraine frequency compared with 39.1% in the amitriptyline group
(P < .05). Both melatonin and amitriptyline also significantly reduced
migraine headache intensity and duration compared with placebo (P < .05).
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 or sodium valproate.
Overall, the evidence supporting melatonin for migraine
prevention is promising but still preliminary. Nonetheless, given the favorable
tolerability and low risk for side effects, melatonin is an option that may be
worth considering for reducing migraine frequency, severity, and duration in
patients with frequent migraine headaches.
Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E,
Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin
3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg
Psychiatry. 2016 Oct;87(10):1127-32.
Abstract
INTRODUCTION:
Melatonin has been studied in headache disorders.
Amitriptyline is efficacious for migraine prevention, but its unfavourable side
effect profile limits its use.
METHODS:
A randomised, double-blind, placebo-controlled study was
carried out. Men and women, aged 18-65 years, with migraine with or without
aura, experiencing 2-8 attacks per month, were enrolled. After a 4-week
baseline phase, 196 participants were randomised to placebo, amitriptyline
25 mg or melatonin 3 mg, and 178 took a study medication and were followed for
3 months (12 weeks). The primary outcome was the number of migraine headache
days per month at baseline versus last month. Secondary end points were
responder rate, migraine intensity, duration and analgesic use. Tolerability
was also compared between groups.
RESULTS:
Mean headache frequency reduction was 2.7 migraine headache
days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo.
Melatonin significantly reduced headache frequency compared with placebo
(p=0.009), but not to amitriptyline (p=0.19). Melatonin was superior to
amitriptyline in the percentage of patients with a greater than 50% reduction
in migraine frequency. Melatonin was better tolerated than amitriptyline.
Weight loss was found in the melatonin group, a slight weight gain in placebo
and significantly for amitriptyline users.
CONCLUSIONS:
Melatonin 3 mg is better than placebo for migraine
prevention, more tolerable than amitriptyline and as effective as amitriptyline
25 mg.
Ebrahimi-Monfared M, Sharafkhah M, Abdolrazaghnejad A,
Mohammadbeigi A, Faraji F. Use of melatonin versus valproic acid in prophylaxis of
migraine patients: A double-blind randomized clinical trial. Restor Neurol
Neurosci. 2017;35(4):385-393.
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.
No comments:
Post a Comment