The latest genetic and biological research shows that migraine is most likely a neurological, not a vascular, disorder and newer treatments in development target peripheral and central nervous systems, according to David Dodick, MD, speaking at American Pain Society's 31st Annual Scientific Meeting in mid-May 2012. Migraine is generally an inherited disorder characterized by physiological changes in the brain involving central neuronal modulation, as well as structural brain changes if attacks occur frequently; so, it is essential that practitioners help patients to utilize preventive strategies.
Dodick, who is professor of neurology at Mayo Clinic in Phoenix, Arizona, noted in his plenary session talk that migraine is among the most prevalent and debilitating medical conditions, afflicting an estimated 10% percent of the world’s population. In the United States, the Institute of Medicine recently reported that 40 million persons have migraine, he said. “While migraine research has been massively underfunded and the disorder often is clinically dismissed as a ‘headache,’ its genetic and biological basis is increasingly coming into focus as the result of considerable scientific advances over the past two decades.”
Current acute migraine medications, such as triptans, were developed to constrict cerebral blood vessels, based on the prevailing concept that migraine is a vascular headache disorder. However, Dodick stated, “I believe that [migraine] activity can begin in the central neurons themselves,” which can be characterized as cortical spreading depression or “activation,” and may also account for the biological basis of migraine aura that occurs in approximately 30% of those who suffer migraine.
Advances in migraine knowledge have led to the development of promising new and selective compounds and therapies for both acute and preventive treatment of migraines. “All effective migraine prevention drugs inhibit cortical spreading depression,” Dodick observed, “including gabapentin and memantine, which are used off-label.” Peripheral and central neurostimulation to prevent migraines is being explored, including deep brain and transcranial magnetic stimulation. Furthermore, a number of newer agents under development target central neurotransmitters and their receptors, including NMDA receptor antagonists, selective 5HT1F, nNOS, ASIC-3 agents, and calcitonin gene-related peptide receptor antagonists, or GEPANTS. Depot injections of monoclonal antibodies are also in development.
Dodick emphasized that practitioners should think about the treatment of migraine in a disease model context, similar to hypertension or diabetes. However, certain migraine risk factors are not modifiable: being female, of low socioeconomic status, experiencing head trauma, and genetics. The basis for preventive treatment is understanding what underlying risk factors for migraine can be modified or eliminated before migraine attacks become more frequent.
Major risk factors include overuse of acute medications, particularly opioids, barbiturates, analgesics and triptans, depression and other mood disorders, obesity, snoring, and excessive caffeine intake. Dodick believes that controlling risk factors can help prevent episodic migraine patients from becoming chronic pain sufferers, and this can be done effectively in primary care settings if practitioners are educated on migraine prevention strategies. For example, he noted that obese people have a 5-fold risk for developing migraine and depressed individuals have a 3-fold higher risk; so treating these risk factors can be an effective prevention strategy.
Dodick further noted, “About 40% of migraine patients are candidates for preventive treatments but only 10% receive them.” In April, the American Academy of Neurology and the American Headache Society announced new guidelines for migraine treatment, he said, which endorse preventive therapies using a wide variety of medications from antidepressants to blood pressure lowering drugs to plant extracts.
These two guidelines documents can be accessed free via Pain-Topics.org as follows:
- Pharmacologic Treatment for Migraine Prevention in Adults [here]
- NSAIDs and Other Complementary Treatments for Migraine Prevention [here]
“The new AAN guidelines illustrate that there are many treatments for which there is substantial evidence to support their safety and efficacy for the preventive treatment of migraine,” said Dodick. “Physicians should use the guidelines to individualize treatment, based on coexisting and comorbid conditions which may be present in their patients, with medications that have the highest level of evidence.” Acute treatments are taken when a migraine attack occurs, but preventive regimens should be taken every day to avoid attacks or lessen their severity and duration. “Some studies have shown that that migraine attacks can be cut in half or more with preventive treatments,” Dodick concluded.
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