/ 4 September 2015

Effective treatment for the queen of brain-pains remains a headache

Sore point: Chronic migraine sufferer Kerry Barton-Hobbs has experienced migraines for about 50 years; even a handful of strong painkillers each day hasn’t alleviated the problem.
Sore point: Chronic migraine sufferer Kerry Barton-Hobbs has experienced migraines for about 50 years; even a handful of strong painkillers each day hasn’t alleviated the problem.

In May last year, foreign tabloids reported the shocking story of an elderly woman in China who stabbed herself in the head with a pair of blue-handled kitchen scissors in an attempt to stop the throbbing pain of a migraine attack.

Even though the veracity of these reports is questionable, sourced from sensationalism-prone tabloid media, the wealth of migraine-pain tales in blogs and scientific journals suggest that this Chinese woman’s experience of debilitating agony is not so far-fetched, even if her solution is.

According to the World Health Organisation (WHO), migraines, a severe and long-lasting type of headache, are a “common worldwide problem” affecting at least one in 10 adults globally.

There is no specific prevalence information available for South Africa, but a Johannesburg-based headache specialist, Elliot Shevel, believes “there is no reason to believe the burden is any less here”.

Data from the WHO’s 2012 global burden of disease study ranked migraine as the fourth most disabling medical disorder for women and the ailment ranked seventh overall. The study compares the disability caused by a day of severe migraine to quadriplegia, the paralysis of all four limbs – and despite the numerous accepted treatments available, a quarter of migraine sufferers lose five days of work over a three-month period.

A 2012 study published in the European Journal of Neurology estimated that the annual cost of the condition for Europe alone is 111-billion euros.

Migraine mistreated
According to a 2013 article in the journal Headache, migraine remains so debilitating because it is a “complex condition which is poorly understood and frequently mistreated”. The authors note that, depending on an individual’s context, migraine is costly to treat, difficult to diagnose and available therapies are not effective for all sufferers and sometimes have “prohibitive” side effects.

Lawrence Newman, president of the American Headache Society, a research organisation that publishes the international peer-reviewed journal Headache, told Bhekisisa that, although treatments for the condition have been developed for many decades and there are more than 100 different drugs used in therapy, they still “don’t work for everyone”.

“In fact, of the medications used for prevention, currently, none have been specifically developed as antimigraine agents,” he explains. “They were all found by accident to have an effect on migraine while being used for other conditions such as hypertension, epilepsy and depression.”

Newman says botox, conventionally used for cosmetic purposes, is one such example but migraine is primarily treated “acutely”, or once the headache has already started, with one of two classes of migraine-specific drugs – ergots and triptans.

He says that health system constraints, health worker and patient education as well as the fact that current drugs are not ubiquitously effective mean that migraine is under-treated and under-diagnosed even in wealthy countries.

Migraine symptoms
The “broad variability of migraine symptoms” – moderate to severe head pain, nausea, vomiting, sensitivity to light, sound, smells as well as dizziness – contribute to migraines being so disabling, according to a 2015 Journal of Head and Face Pain study.

The article further explains that migraines, which can last from four to 72 hours, are subdivided into migraines with “aura”, sensory disturbances that pre-empt the onset of the headache, and those without.

“Auras, characterised by visual symptoms (spots of light, zigzag lines or greying out of vision), sensory symptoms (tingling and numbness), or language disturbances, occur in 20%-30% of people with migraine.”

According to Newman, in the United States, about half of migraine sufferers do not get the treatment they need and Shevel estimates that even fewer South Africans are untreated, causing considerable disruptions to daily life, work, relationships and mental and physical wellbeing.

Available medicines 
The first drug developed for migraine in the 1930s, ergotamine, works by constricting blood vessels in the body, says Shevel.

“They work because during a migraine attack blood vessels dilate and send pain messages to the brain – often felt as throbbing.”

But these have serious side effects because they restrict blood flow to many parts of the body and are dangerous for people with heart conditions. They are also only used once a migraine has started.

The second class of medication developed for use once a migraine has already started is called triptans and has been used since the early 1990s, according to the WHO. They also work by constricting blood vessels but are more focused on the blood vessels in the head, making them safer than ergotamine, says Shevel.

But they still have side effects. According to the American Headache Society, which sets US guidelines for treatment, these can include “nausea, muscle tightness, fatigue, rapid heart rate, numbness as well as a burning sensation over the skin”. The society, in its guidelines, says triptans should not be used by people with high blood pressure, heart problems or while pregnant.

But triptans are still “not effective for all migraine patients and will not stop every headache even in those patients who do benefit from the drugs”, it notes.

New drugs
A number of pharmaceutical companies are developing a new class of drugs that may work specifically for migraine as well as for prevention.

Andy Gray from the University of KwaZulu-Natal’s pharmacy department explains that there is evidence that a certain peptide, which is a chain of amino acids that are the building blocks of proteins, “is involved in the activation of nerve pathways that contribute to the development and persistence of a migraine attack”.

The drugs are being developed to reverse the action of this peptide and the theory is that this will in turn make migraines less painful and less frequent, he says.

One of these drugs, Telcagepant, developed by the pharmaceutical company Merck & Co, got to the second phase of clinical trials (when the drug is tested on a small number of people) and had to be stopped because of liver toxicity, according to a 2014 paper published in The Lancet journal.

The authors note that although the drug lessened the severity and frequency of migraine it was dangerous to take daily as preventative therapy because of the damage it caused to the livers of participants.

Drugs in the pipe-line
Although this trial was unsuccessful, Newman says other studies, particularly those involving CGRP (calcitonin gene related peptide) antibodies, as opposed to antagonists, are showing promise.

“These agents, in fact, any new agent, offers promise because the treatments we currently have are not totally effectual. If the preliminary data is supported, then these new agents may offer the potential to help significantly more of our patients and these could become available within the next three years,” he says.

However, the WHO says that less than half of migraines are even diagnosed globally and, coupled with the “nonavailability” of existing drugs in many parts of the world, “the condition contributes significantly to global disability”.

In the WHO’s 2011 publication on headache disorders, it says even high-income countries have problems with patients being able to get access to these drugs.

This is a result of the “low priority given to headache disorders and under-recognition of their impact” and the organisation calls for “better availability, better organisation and delivery of headache services”.

If headaches and migraines featured more prominently on the global health agenda more may be discovered about “how, or how much, they affect many of the populations of the world”, the WHO publication noted, or how healthcare and other resources can be used to mitigate their effects of migraines and headaches – “which are among the most prevalent disorders of mankind”.


New drug therapies, new hope? Not so fast

The discovery of calcitonin gene-related peptides (CGRP), an element of a protein, and its association with migraine in the 1980s was a “significant breakthrough in science” but new drugs being developed using CGRPs “are not the medical breakthrough pharmaceutical companies claim they are”, according to Johannesburg-based headache specialist Elliot Shevel.

He says that, while these new drugs may have some therapeutic benefit, their role in migraine treatment is over-emphasised. 

Andy Gray, from the University of KwaZulu-Natal’s pharmacy department, explains that “there is evidence that CGRP is involved in the activation of nerve pathways that contribute to the development and persistence of a migraine attack”. 

CGRP receptor antagonists, currently being developed and tested by the pharmaceutical company Allergan, work by “blocking the receptor which interacts with CGRP”. Initially touted as preventative therapy by the pharmaceutical company Merck, it was found that during the second phase of trials to test its drug, Telcagepant, the medicine caused damage to the liver; its development was stopped. 

But for Shevel the controversy doesn’t lie in the failure of Telcagepant but in the claims made as bout where the drugs work in the human body. “Nowhere in scientific literature is it proven that CGRP is found in the blood in the human brain [intra-cranial], which is what is being claimed,” he explains. 

He says that the only evidence that CGRP is located inside the brain comes from studies done on cats and, in humans, the peptide has only been proven to be located in the blood of the scalp – the extracranial blood. 

In a 2014 article published in the international journal Headache, Shevel says that, while “studies on laboratory animals have provided medical science with much valuable information, care should be taken not to extrapolate the results of animal studies too freely to humans because often there are marked variations between species”. 

“There are claims that these drugs are the breakthrough we need in migraine treatment because they work differently to the current drugs. In other words, they are working inside the brain and not on the extracranial blood vessels like the triptans [drugs currently widely used to treat migraine],” he says. 

According to Shevel these new drugs will only help migraine sufferers who also have heart problems as they won’t constrict blood vessels in other parts of the body like triptans may do in some cases. “But for the vast majority of migraine sufferers with an arterial component to their pain, the new drugs will perform no better than the old ones,” he says.


Pain and the anticipation of more pain 

“My earliest childhood memories are as a four year old with a sore head,” says social justice activist Kerry Barton-Hobbs. 

In the fifty years since then, not much has changed and Hobbs experiences migraine headaches almost constantly. She has a singular memory of being migraine-free for two months a few years ago but her daily reality is pain, medication and the anticipation of more pain. 

“When a migraine starts sometimes the pain will be immediate but other times it will start slowly and increase in intensity,” she says. 

Hobbs has had migraines that last for a few hours, a day or two and sometimes a couple of weeks. “Sometimes I experience daily migraines that lift and return within a few hours,” she says. 

And during these “attacks” Hobbs is nauseous, sensitive to light and her perception of depth is impaired. 

The onset and duration are unpredictable and so is the pain. “The pain moves around my head – from migraine to migraine – and within one migraine. Sometimes it feels like a blade has been inserted into my head. Sometimes my head pounds. Sometimes, especially when located over an eye, it is painful to keep my eyes open,” she explains. 

Despite this, and with the assistance of a myriad of medications, Hobbs has raised a now-adult son and pursued a career in the non-governmental organisation sector. “Sometimes, like today, the pain level is low enough to push through and do some work. But other times it is excruciating and debilitating, and the best I can do is to medicate and lie very still in the dark and quiet – and wait for it to shift.” 

Each day she takes up to eight pain tablets but if she judges, at the onset of the migraine, that the pain is particularly bad she adds two different anti-migraine drugs, a muscle relaxant, an anti-inflammatory and sometimes more painkillers. 

But this regimen came through trial and error and she has tried many other medications, and experienced the side-effects, over the years. “I remember when I tried anti-epilepsy medication because it can prevent some people’s migraines I had an out of body experience where I could see people were talking to me but I had no idea what they were saying.” 

She says that “you have to try everything in the hopes that eventually something will work”. 

Like many migraine sufferers she does not know what causes her headaches but she avoids certain ‘triggers’ like tobacco smoke, preservatives, sugar, gluten, lactose and too much stress. “It’s difficult to maintain this and I do sometimes battle to manage my career and other obligations, but it’s become a way of life, and I push through when I can,” she says. “And collapse when I can’t.”