CGRP Blockers & SRAs – The New Faces In Research For Migraine Management

CGRP stands for Calcitonin Gene-Related Peptide. It is a calcitonin group compound made up of polymers of amino acid monomers. CGRP is manufactured in the human body in the nerve cells (neurons) of the central nervous system and the peripheral nervous system.

Research – New Migraine drugs In The Pipeline (1)

So what is the function of CGRP? Of the many functions, CGRP is a powerful vasodilator and it contributes significantly in the transmission of pain message through the body. It is also believed to play a critical role in cardiovascular homeostasis as well as in processing noxious stimuli that has the potential to damage the tissues of the heart.

The development of drugs which are essentially CGRP receptor antagonist is in the pipeline aimed at helping migraineurs the world over cull the pain of their migraine episodes. How does the CGRP receptor antagonist do this? It has been observed that during the onset of a migraine attack, CGRP binds to CGRP receptors and activates these receptors which then transmit pain signals. CGRP receptor antagonist prevents the CGRP from binding on to CGRP receptors thus circumventing the transmission of pain signals causing migraine pain.

Telecagepant was such a CGRP receptor antagonist drug developed by Merck & Co. and was undergoing Phase III clinical trials but the trials were abandoned after identification of two patients with significant elevations in serum transaminases indicating liver damage. However, similar drugs without such side-effects are now being designed. CGRP receptor blockers also significantly reduce nausea and are more desirable in total benefit than triptans. As per Peter Goadsby, MD, PhD, director of UCSF’s Headache Center, “So this is a way for it to be effective and adds a safety bonus to the patients and it seems to be better tolerated.” (2)

There is another approach to drug design and development aimed at reducing the misery of migraineurs and it comes from the side of serotonin activity. In this class, one investigational drug of note is Lasmiditan thought of by Eli Lilly & Co and being designed to treat acute migraine by CoLucid Pharmaceuticals. These drugs are technically serotonin receptor agonists and selectively bind to the 5-HT1F receptor subtype. Unlike triptans these drugs do not constrict the heart vessels and have lesser side-effects. Trials have shown that administration of this drug reduced migraines to almost nothing within a two-hour period in almost 60% of the patients also tackling nausea and photophobia beautifully. The drug is expected to be ready by 2014. As per Dr. Goadsby, “Lasmiditan is now that finished its phase two studies and clearly works. It does not have the same sort of liver effects as its predecessors and will move on into phase three. That is again for acute migraine treatment. So it is a safe and totally different action than what we currently have.” (2)

 

SOURCES:

1. Image by Ponsulak; Freedigitalphotos.net; March 2012; http://www.freedigitalphotos.net/images/view_photog.php?photogid=1983
2. Cutting Edge Treatments For Migraines: More Than Just A Headache; Ivanhoe.com; March 2012; http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=29106&channelid=CHAN-100018

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Co-morbidity of Migraine and Depression In Women

Most of us are aware that migraineurs have some comorbid conditions like generalised anxiety disorder, cardiovascular conditions and gastrointestinal disturbances. Research now has it that migraineurs especially women who have either experienced repeated episodes of migraines in the past or continue to have migraines are more likely to experience depression.

Women Migraineurs Very Likely To Develop Depression (1)

In fact another report goes on to suggest that the most ‘important’ comorbidity of migraines is depression with as many as 40% of all migraineurs also suffer from forms of depression. (2)

New research released on 23^rd of February which was presented at the American Academy of Neurology’s 64th Annual Meeting showed that migraining women specifically had a higher risk of almost double for developing depression than those women who did not experience migraines.

This study had examined the medical history of 36,154 women participants. The whole population studied were classified into 4 groups:

• Women with migraines and experiencing aura
• Women with migraines who do not experience aura
• Women who had suffered migraines in the past but have not in the last one year
• Women who never had migraines

It was observed after collection and analysis of data that as many as 18% of the studied population had either current or past history of migraines and that of this group of 6, 456 women almost half of them developed depression 14 years on.

Another observation of note was that the results in terms of the probability of developing depression for women migraineurs remains almost same regardless of the type of migraines they experience (i.e. with or without visual aura)

The results did not vary substantially, regardless of the type of migraine. Those with aura, which is described as visual disturbances that appear as flashing lights, zigzag lines or a temporary loss of vision, had the same risks as other types of migraine.

According to Tobias Kurth, MD, ScD, with Brigham and Women’s Hospital in Boston and Inserm in France and a Fellow of the American Academy of Neurology, “This is one of the first large studies to examine the association between migraine and the development of depression over time. We hope our findings will encourage doctors to speak to their migraine patients about the risk of depression and potential ways to prevent depression.” (3)

This is a cue to doctors and headache specialists who treat migraineurs for assessing the patient for possible symptoms of depression and chalking out an appropriate management program for them.

SOURCES:

1. Image by David Castillo Dominici; Freedigitalphotos.net; February 2012; http://www.freedigitalphotos.net/images/view_photog.php?photogid=3062
2. Comorbidities of Migraine – Page 4; Lisa K Mannix, MD; February 2012; http://www.headaches.org/pdf/CME_Mono02.pdf
3. Migraine Increases Risk Of Depression In Women; Medical News Today; February 2012; http://www.medicalnewstoday.com/articles/242091.php

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Acupuncture: A ‘Yes’ or A ‘No’ For Migraineurs?

This post has been drawn from Medicine News Today for the benefit of migraineurs:

In order to find out the effect of acupuncture compared with sham acupuncture in treating migraines, a team of investigators carried out a randomized controlled human trial. 480 individuals at 9 hospitals in China who experienced migraines for over one year, with two or three migraines in the 3 months prior to the investigation, were enrolled to participate in the study.

The researchers randomly assigned the volunteers to four groups. Those in one group received sham acupuncture, while participants in the other three groups received different types of acupuncture. Their ages ranged from 18 to 65 years.

In the United States and England, migraines affect approximately 16% to 18% of women and 6% to 8% of men. Evidence on how effective acupuncture is at treating migraines is mixed, as some studies suggest it is the placebo effect, instead of a therapeutic effect that relieves symptoms. Acupuncture distinguishes between real acupuncture points and non-acupuncture (sham) points.

Dr. Fan-rong Liang, Chengdu University of Traditional Chinese Medicine, Chengdu, China, explains: ”We found that the outcomes following acupuncture were significantly better than with sham acupuncture during weeks 13-16, but the effect was clinically minor.”
After 16 weeks, approximately half to three-quarters of participants were better after sham acupuncture and proper acupuncture. The researchers said: ”Acupuncture has a large effect on treating migraines, but the specific therapeutic effect may be minor.”
In an associated commentary, Dr. Albrecht Molsberger, Ruhr University, Bochum, Germany and the University of North Carolina, explains that according to previous evidence, acupuncture helps treat severe migraine attacks.

Molsberger explains: ”On the basis of the existing evidence, acupuncture should be an option for the first-line treatment of migraine to supplement other non-pharmacologic treatment options.”
In a second randomized controlled trial, investigators in the Netherlands enrolled 490 patients from 64 general practices, 233 of them attended consultations to assess treatment of their migraines, as well as 257 in the control group. The researchers set out to examine whether a proactive approach by primary care physicians to patients with suboptimal migraine treatment would result in improvements.

In the Netherlands, only 8% to 12% of all patients with migraines used prophylaxis, while a considerable amount of individuals used too much medication for migraine attacks.

Even though more individuals took prescription medication to prevent migraines as a result of the approach, the researchers observed no clinically relevant effect after six months.

Dr. Antonia Smelt, Leiden University Medical Center, Leiden, the Netherlands, with co-authors, explained: ”We found no clinically relevant effect of a proactive approach to migraine in primary care for patients who were using two or more doses of triptan per month.”

The researchers conclude:
“It is possible that the intervention resulted in better treatment for patients not using prophylactic medication at baseline who had two or more attacks of migraine per month. Future interventions in primary care should target these patients.”

 

SOURCE:

Migraine – The Enigma Of Trial Results; Grace Rattue; Medical News Today; January 2012; http://www.medicalnewstoday.com/articles/240139.php

Exercise just as good as drugs at preventing migraines, Swedish study suggests: Science Daily

ScienceDaily (Oct. 10, 2011) — Although exercise is often prescribed as a treatment for migraine, there has not previously been sufficient scientific evidence that it really works. However, research from the Sahlgrenska Academy at the University of Gothenburg, Sweden, has now shown that exercise is just as good as drugs at preventing migraines.

Doctors use a variety of different methods to prevent migraines these days: on the pharmaceutical side a drug based on the substance topiramate has proved effective, while non-medical treatments with well-documented effects include relaxation exercises.

No previous evidence 

Exercise is also frequently recommended as a treatment, though there has not been sufficient scientific evidence that it really has any effect on migraine patients.

In a randomized controlled study researchers from the University of Gothenburg’s Sahlgrenska Academy have now analysed how well exercise works as a preventative treatment for migraines relative to relaxation exercises and topiramate.

40 minutes of exercise
Published in the journal Cephalalgia, the study involved 91 migraine patients, a third of whom were asked to exercise for 40 minutes three times a week under the supervision of a physiotherapist, with another third doing relaxation exercises, and the final third given topiramate. The study lasted for a total of three months, during which the patients’ migraine status, quality of life, aerobic capacity and level of phyical activity were evaluated before, during and after their treatment. Follow-ups were then carried out after three and six months.

Exercise just as effective
The results show that the number of migraines fell in all three groups. Interestingly, there was no difference in the preventative effect between the three treatments.
“Our conclusion is that exercise can act as an alternative to relaxations and topiramate when it comes to preventing migraines, and is particularly appropriate for patients who are unwilling or unable to take preventative medicines,” says Emma Varkey, the physiotherapist and doctoral student at the Sahlgrenska Academy who carried out the study.

Journal Reference:
E. Varkey, A. Cider, J. Carlsson, M. Linde. Exercise as migraine prophylaxis: A randomized study using relaxation and topiramate as controls. Cephalalgia, 2011; DOI: 10.1177/0333102411419681

De-mystifying Migraines In Women

I was struck by the statistics on migraineurs worldwide published by the WHO. Apparently, 303 million people the world over suffer migraines, out of which women account for 70% of the patients. India alone has 100 million sufferers and the US has 30 million patients. The report went on to add that it is estimated that 20 million migraine attacks happen everyday!!!! Staggering by any scale.

Though a lot of cutting edge research has been done, especially in the last decade to control this beast, scientific reports still grapple with unknowns, and are still clueless on issues such as why or how magnesium release regulates calcium ions in the neurons or why a certain chain of events takes place in the cranium that bring on migraines or even why they wind up.

With so much still in the grey, one wonders when and if help will come from drugs that will be safe to consume in the long run or if there are any strategies out there to shake this neurological disease.

In my book, ‘Migraines for the Informed Woman’, I have attempted to simplify the esoteric jargon of research papers and scientific material on migraines. After more than one decade of trying most therapies, I have come to the conclusion, that some work and others that are not as effective. More importantly, I have come to realise that certain mixes of therapies done simultaneously work wonders.

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