One in seven people around the world suffer from migraine. In the UK, migraine has a crippling economic effect, with approximately 25m days lost every year, costing the country £2.3bn. But while the condition has been studied since the time of the ancient Greeks – who attempted to treat it with trepanning, by drilling a hole into the skull to release evil spirits – it remains poorly understood with few adequate treatments.
What is it?
Migraine is an inherited disorder characterised by episodes of throbbing head pain. Many patients also report nausea, sensory hyperactivity, with ordinary volumes of sound or light seeming intolerably loud or bright. Others experience aura or neurological abnormalities such as vertigo, temporary blindness and numbness. Some rare types, such as hemiplegic migraine, are single gene disorders, with a particular mutation predisposing individuals to neuronal hyperactivity, meaning that areas of the brain involved in interpreting sensory events can be easily activated. But most common forms are polygenic – in which a constellation of genes contribute. Various environmental triggers are also strongly associated with migraine, including stress, skipping meals and lack of adequate sleep.
Our understanding of the neurological processes is still limited, but scientists are starting to put some of the pieces together. “We know that dilation of blood vessels may play a role and some of the newer treatments try to inhibit this,” says Elizabeth Loder, professor of neurology at Harvard medical school.
Why don’t we know more?
Serious research into migraine began only relatively recently, as for a long time many doctors believed that it was a psychosomatic condition produced by people being unable to deal with stress. “It was a disorder that most obviously affected women and so wasn’t taken as seriously,” Loder says. “And it’s a pain disorder. Pain is subjective: we don’t have any way of measuring it, which can make it very hard for people to believe it’s real. Plus, on top of all of that, it’s episodic, so between attacks, sufferers may look perfectly well.”
The fact that migraine is researched at all owes a lot to the development of the medication methysergide in 1960, which was found to eliminate headaches in weeks. The drug is no longer commercially available as it was found to have serious side-effects, but its legacy remains. What had been perceived as a psychological condition clearly had a biological basis. “The market is, of course, very big,” Loder says. “It’s a common disorder, it lasts decades. So, that made pharmaceutical companies sit up and take notice; money poured into the field; it improved and professionalised research.”
However, migraine receives much less funding, compared with similarly debilitating conditions. Studies looking at money allocated by the US National Institute of Health, for example, have shown that migraine is considerably underfunded.
Are women more prone to migraine?
Migraine is extremely common in both sexes but statistics suggest that it is more prevalent in women. Reports in the US estimate that, while 12% of the population has had an attack in the past year, this rises to 18% when women alone are considered.
Scientists suspect that cycling ovarian steroid hormones, in particular the drop in oestrogen that occurs during the menstrual cycle, are particularly provocative, especially for those genetically susceptible to the disorder. The dissipation of these hormones with age explains why some women find that migraine attacks become less common as they get older.
“I think women with the disorder are more likely than men to be accurately diagnosed with migraine,” Loder says. “Women see doctors more and are less likely to be hesitant to complain about head pain than men are. Some research shows that men with the disorder tend to be investigated for other causes of headache, suggesting that doctors have a cognitive bias and they don’t think of migraine as readily as they do with women.”
So, does migraine improve with age?
The disorder is most active and troublesome during the middle years of life, when people would otherwise be at their most productive, and typically don’t have as many competing causes of disability. But as you get older, the effects usually seem to diminish.
“Clinically it’s extremely unusual to see people in their 60s, 70s and older saying that their migraines are just as bad as they have always been,” Loder says. “It does happen, but it’s so uncommon that everybody sits up and takes note.”
It is thought that some of the processes that produce a severe migraine cannot happen as efficiently in older people. As we age, our arteries become stiffer and some of the vascular events that cause migraine can’t happen as easily.
What treatments are available?
A class of medications called triptans are typically prescribed. However, about 30-40% of migraine patients don’t respond to the first triptan prescribed, and, for those who don’t respond at all, there are few alternatives – no new migraine drugs have been developed since the early 90s. In addition, pain relief from triptans is relatively slow – they often take 45-90 minutes to take effect.
For chronic migraine sufferers – those who experience headaches on more than 15 days a month – the effectiveness of treatment is particularly poor, with many medications causing side-effects such as sedation, dizziness and mood change.
“The problem is that a number of the drugs currently prescribed weren’t originally developed for migraine,” says Brendan Davies, consultant neurologist at University Hospitals of North Midlands and a trustee of the Migraine Trust. “They were initially developed for epilepsy or depression, before they were found to be potentially beneficial for migraine, and so they work on pathways in the brain which may not be migraine specific.”
Are better treatments being developed?
Triptans are referred to as “abortive medicines”, as they treat an individual migraine attack, but drug companies are looking at injections that could prevent migraines from starting. Levels of one particular protein, CGRP, a very powerful vasodilating substance, have been found to shoot up during migraine attacks. Another protein, PACAP, is also thought to be a promising new drug target. So far, the companies have invested heavily in developing antibodies that can bind to CGRP molecules and block them. These are typically administered via monthly injections, rather than daily tablets. “So far, the results of all the published studies suggest that these treatments do work better than placebo,” Loder says. “They don’t completely eliminate headaches, but they reduce their frequency. In one recent study of a group who had, on average, 18 headache days a month, people who took the drug had an average reduction of 6.6 days compared with 4.2 days in those who took a placebo. The difference between drug and placebo is modest but there is an effect.”
However, so far only half of migraine sufferers appear to respond to CGRP antibodies, and there is no way of predicting who will benefit. In addition, little is known of the long-term consequences of blocking CGRP. “I’m cautiously optimistic,” Loder says. “First, these treatments are likely to be very costly, and second, CGRP is very widely distributed through the body, and there’s some suggestion from animal studies that there could be long-term side-effects. They could turn out to be safe medications, but we’re speculating. If you think about antibodies which have been developed for common neurologic illnesses such as MS, there have been long-term safety concerns.”
Source: The Guardian