Be sure to read below the abstracts of published papers from Bordini et al. and Mário Peres et al. which bring us information about two sister molecules, one exogenous and the other endogenous.

Looking at their structural similarity, it is not surprising that they can have effect on headaches, even though, at least at first, different

Bordini et al. present an extensive review on indomethacin, since this molecule was synthesized in 1963 and marketed by Merck as Indocin.

Pharmacological aspects are described, with a molecular bioavailability of approximately 98%, peak plasma concentration of 0.5 -2 hours, average half-life of 4.5 hours, hepatic metabolism and renal excretion.

Their mechanisms of action are diverse, with vasoconstriction, CSF pressure reduction, reduction speed of blood flow, inhibition of trigeminovascular response and reduced Calcitonin gene-related peptide and Vasoactive intestinal polypeptide. For those who wondered how indomethacin action was in headaches associated to physical effort, here is the explanation.

Curiously headaches responsive to indomethacin are listed. They are classified into 3 groups: 1) trigeminal autonomic headaches: cluster headache, paroxysmal hemicrania and hemicrania, continua; 2) Headache related to exercise or Valsalva induced headaches: Primary Cough Headache, Primary Exercise Headache and Primary Headache Associated with Sexual Activity and 3) Miscellaneous: Primary Stabbing Headache, Nummular Headache and Hypnic Headache

In addition, the authors note an alert regarding the responsiveness to the use of indomethacin in secondary headaches mimicking trigeminal autonomic headaches. Good therapeutic response is revealed as no benignity indicative of the disease or primary headache.

The authors approach the headache caused by indomethacin, which occurs in about 20% of those who use it continuously. Also, a critical approach regarding to the absolute response with this medication use for paroxysmal hemicrania and hemicrania continua, revealed that this absolute response it is not always real, since up to 30% of the patients are not responsive to the treatment.

Anyway, an excellent review is at our disposal commenting about an intriguing medication that still brings a lot of discussion and curiosity in daily life.

Dr. Mário Peres’ study group, for years dedicated to the pathophysiology of migraine and therapeutical effect of melatonin on this medical condition, is presenting a randomized placebo-controlled study about the melatonin efficacy and good tolerability as preventing treatment for migraine.

This study compared melatonin 3 mg, amitriptyline 25 mg and placebo. The results were encouraging. Both melatonin and amitriptyline were superior in the primary outcome (reducing the frequency of episodes of migraine per month, in days) compared to placebo. However, melatonin has shown higher outcomes than the amitriptyline in one of the secondary outcomes, which was the number of patients with more than 50% of improvement in migraine frequency.

Regarding to the tolerability of medications, no severe adverse effect occurred. Melatonin and placebo groups were similar considering adverse events occurrence.

In the scenario of topiramate as the last medication approved by the Food Drug Administration for migraine prevention, in 2004, melatonin appears as a new therapeutic option with low cost and good clinical results.

The only current hindering factor is the availability of this drug in the Brazilian market. The Brazilian regulatory agency, the National Health Surveillance Agency or ANVISA has not yet authorized its marketing in the country, "However, the legislation ensures that patients who receive this product prescription from a physician can import for own use, either via hand luggage or even from e-commerce." (ANVISA press assistant)

Read the abstracts accessing this link:

Emilia C. Bordini, Carlos A. Bordini, Yohannes W. Woldeamanuel, Alan M. Rapoport. Indomethacin Responsive Headaches: Exhaustive Systematic Review With Pooled Analysis and Critical Appraisal of 81 Published Clinical Studies. Headache 2016; 422-435.
(http://onlinelibrary.wiley.com/doi/10.1111/head.12771/abstract)

Andre Leite Gonçalves, Adriana Martini Ferreira, Reinaldo Teixeira Ribeiro, Eliova Zukerman, José Cipolla-Neto, Mario Fernando Prieto Peres. Randomised clinical trial comparing melatonina 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;0:1–6.
(http://jnnp.bmj.com/content/early/2016/05/10/jnnp-2016-313458.full)

Anvisa guidelines related to Melatonin:
(http://portal.anvisa.gov.br/informacoes-tecnicas13/-/asset_publisher/FXrpx9qY7FbU/content/melatonina/219201/pop_up?_101_INSTANCE_FXrpx9qY7FbU_viewMode=print&_101_INSTANCE_FXrpx9qY7FbU_languageId=pt_BR)