Drugs for Acute Treatment of Migraine

Introduction

Migraine headache is the most common and probably the most costly neurological disorder in the US, affecting more than 36 million Americans. Although this condition is very common, there was no specific treatment given to migraine sufferers until recently. Published in The Washington Post on June 17, a medical media article entitled “New class of drugs being tested for migraine prevention shows promise” reported that three different pharmaceutical companies have shown results of the studies conducted on a new class of drugs .These drugs are developed specifically to treat migraines. The article states that these new drugs are designed to have minimal side effects and they work by decreasing the amount calcitonin gene-related peptide, the key factor causing migraine pain, in the body.

For years, migraine sufferers are prescribed treatments designed or developed for other conditions. These include antidepressants, antihypertensive drugs, calcium and beta channel blockers and other vitamin supplements (Silberstein et al. 2012). These treatments often come with serious side effects, low adherence rates and low efficacy rates (Scher et al. 2012; Lafata et al. 2009; Loder & Rizzoli 2011). About 20 percent of these migraine sufferers who experience chronic migraine and are treated in emergency rooms, have been prescribed opioids and barbiturates. Although these powerful drugs induce migraine progression (depending on doses),they are sometimes ineffective as they worsen headaches, and often risks addiction (Bigal & Lipton 2009).

This paper provides an overview of the main issue discussed in the media article from both pharmacological and social perspective. Several new medications are under development for preventing migraine pain and the mechanism of the actions of these drugs are covered in this paper . The controversy surrounding the effectiveness of the new drugs and their extensive uses is also discussed in the paper.

Drugs for acute treatment of migraine

Previously, several different drugs were used in the acute treatment of migraine. Although none of these were developed specifically for migraine they had various mechanisms of action,   inhibiting the part of the brain that generated migraines, including calcium and sodium channel blockers, beta blockers and blocking gap junctions. Antidepressants, anticonvulsants, antihistamines, and narcotic pain relievers are sometimes used in order to relieve patients of migraine attacks.Even though they don't address the pathophysiology of migraines, some over the counter medications such as Paracetamol ,Caffeine and NSAIDS can also help reduce migraine pain along with some vitamins and mineral supplements.

CGRP receptor antagonists

The published media article highlights that three pharmaceutical companies- Amgen, Eli Lilly and Teva- reported that the new class of drugs works by decreasing levels of calcitonin gene-related peptide in the body. Calcitonin-gene related peptide (CGRP) is an amino acid peptide produced by peripheral and central neurons in our body and acts as a potent vasodilator. It is implicated in the transmission of pain signals in both central and peripheral nervous system, and is released during severe migraine attacks (Ho, Edvinsson & Goadsby 2010; Villalón & Olesen 2009).

Although none is available or approved for medical use, quite a few CGRP receptor antagonists are found effective in treating migraine (Ho et al. 2008; Diener et al. 2010; Olesen et al. 2004). Triptans, a class of tryptamine based drugs,are strong inhibitors of CGRP release (Amrutkar et al. 2012). They relieve headaches by reducing concentrations of circulating CGRP( Goadsby & Edvinsson 1993).The sumatriptan tablet was the first drug designed especially for acute migraine therapy and acted with higher specificity on serotonin receptors.Despite the fact that triptans are extremely effective for  many individuals (Thorlund et al. 2013), they come with significant limitations including the recurrence  of migraine symptoms. They are also contraindicated in people suffering from untreated vascular risk factors or in patients with severe vascular conditions (Dodick  et al. 2004).

Three other antagonists of CGRP-receptor that belong to the gepant class of drugs, Olcegepant, Telcagepant and Rimegepant have been tested in humans through different trials, resulting in excellent tolerability and medical benefit. In a study with 126 migraine patient, olcegepant was found effective (Olesen et al. 2004); unlike triptan, these antagonist were found to be safe in patients suffering from vascular conditions. But since the drug could only be given intravenously, it was not developed further. The development programme for the antagonist Telcagepant was carried out for an extended period of time and was found effective in acute therapy of migraine (Ho et al. 2008). In a study conducted, migraine patients were given daily doses of Telcagepant for 3 months (Ho et al. 2014) ; but the trial was terminated early when 13 patients showed  marked elevations in liver transaminases causing liver toxicity. In the placebo-controlled clinical study which tested the efficacy of migraine treatment using antagonist Rimegepant, 885 migraine patients were randomly treated with doses of a drug designed similar to Sumatriptan. The drug was found to relieve patient off severe pain 2 hours after the dosage; this result was much better compared to that of the placebo drug.But the development of this antagonist was terminated for unknown reasons (Peroutka 2013). Although, these studies added to the growing evidence that calcitonin gene-related peptide antagonists play crucial role in the pathogenesis of migraine, they may cause severe side effects and short term tolerability.  

Drugs for preventive treatment of migraine  

Fully humanised monoclonal antibodies against CGRP receptors have been developed as an alternative and better approach to block calcitonin gene-related peptide transmission in the treatment of severe migraine. Results from clinical trials, carried out by three pharmaceutical companies, have shown significant relief from migraine pain and minimal side effects when compared to placebo (Dodick et al. 2014; Dodick et al. 2014) . The clinical trials were performed in Phase I and In Phase II. Phase I clinical trials involved testing the potency of these antibodies for the first time in a very small population and the Phase II clinical trials involved further testing the efficacy of the antibodies in a much larger population.