Research Offers Hope for Headache Sufferers

by Guy McKhann, M.D.

December 10, 2008

Many people suffer from headaches, and the most common cause—except on the morning of New Year’s Day—is migraine. Migraine is a chronic problem that is three times more common in women. It can occur at almost any age but most often affects women between the ages of 30 and 39. Household surveys in the United States indicate that 17.5 percent of women and 5.5 percent of men report at least one migraine attack per year. Of these, 3.4 million women and 1.1 million men have at least one attack of headache per month.

When severe, the headache, nausea and sensitivity to light and sounds that signify a migraine attack can debilitate a person for hours or even days. A complex disorder, migraine involves genetic, behavioral and environmental factors. I won’t spell out these details, but you can visit one of the many informative Web sites on the subject, such as the migraine section of (How’s that? A Hopkins doctor sending you to a Mayo Clinic site? This is part of the new, nonpartisan approach to problem solving!)

Doctors have tailored treatments for migraine to the disorder’s presumed mechanisms. For many years, the predominant theory was that migraine resulted from the dilatation of blood vessels over the surface of the brain. Thus doctors prescribed medications such as ergotamine to constrict vessels during acute attacks. Widely used newer medications, known as triptans, work in part by altering a vascular mechanism. Triptans work marvelously for some patients, but not all. Because triptans constrict blood vessels, some at-risk patients could experience cardiac problems.

In recent years, evidence has suggested that some nerve factors may play as important a role as vascular effects in migraine. Nerves release substances that might dilate blood vessels or activate pain systems in the brain. Researchers have observed one such substance, calcitonin gene-related peptide (CGRP), to be widely present in both the peripheral and central nervous system.

CGRP acts by binding to specific receptors on blood vessels and nerves. Twenty years ago, Peter Goadsby, one of the giants in the field of headache research, noted that nerves released CGRP to the head at the time of migraine attack. He postulated that blocking the action of CGRP might alter migraine. Now investigators at Merck have carried out a large study using just that approach on 1,380 subjects with migraine. They compared patients receiving a compound that blocks the CGRP receptor, telcagepant, with those receiving a commonly used triptan and with those receiving no therapy. The results indicate that telcagepant and the triptan were equally effective in stopping headache. However, the CGRP subjects had far fewer side effects.

This study is important for a number of reasons. First, it involves exploiting a newly hypothesized cause of migraine, based on many years of research. Second, it may develop into a treatment for patients who do not respond to existing medications. Finally, telcagepant may be safer than other migraine drugs, such as triptans.

Of course, telcagepant isn’t ready for clinical use just yet. Researchers must conduct larger clinical trials, perhaps for longer periods of time. It may be several years before this or a similar agent becomes available. But this research is a good start.

Last month I wrote an article about getting involved in brain research. This study of migraine emphasizes why. At a certain point, development of a new medicine requires carefully designed trials in humans to compare the new approach with old ones and, where possible, with patients receiving no treatment. In this case, people with migraine are the human subjects we need in order to make progress and get treatments through the regulatory hoops.