Research Increasingly Points to Migraine as Neurological (vs. Vascular) Disorder

HONOLULU, HI—Recent research has resulted in a very rich pipeline of new agents to treat migraine, said David Dodick, MD, in presenting the Global Year Against Pain Lecture at the American Pain Society's 31st Annual Scientific Meeting.

The 2011 Institute of Medicine report, Relieving Pain in America, has focused attention on headache: approximately 48 million Americans experience a headache almost daily and about 900,000 Americans “will suffer a migraine attack today,” said Dr. Dodick, professor of neurology at Mayo Clinic in Phoenix, AZ. “We are in desperate need of more selective drugs.”

Previously, migraine was believed to be entirely vascular in nature; now, migraine is understood as an inherited neurological disorder involving central neuronal modulation. “I believe that [migraine] activity can begin in the central neurons themselves,” he said. This can be characterized as cortical spreading depression or “activation,” which may also account for the biological basis of migraine aura that occurs in approximately 30% of those who suffer migraine.

Dr. Dodick presented an overview of research that has resulted in a greater understanding of the genetic and pathophysiological basis of migraine, which has in turn led to development of agents that target central neurotransmitters and their receptors. A number of these agents are in Phase 2 and 3 clinical trials, including NMDA receptor antagonists, selective 5HT1F, nNOS, and ASIC-3 agents, and calcitonin gene-related peptide receptor antagonists, or GEPANTS. Depot injections of monoclonal antibodies are also in development.

“All effective migraine prevention drugs inhibit cortical spreading depression,” he said, including gabapentin and memantine, which is used off-label. Peripheral and central neurostimulation to prevent migraines being explored included deep brain and transcranial magnetic stimulation.

He emphasized that practitioners should think about the treatment of migraine in a disease model context, in much the same way as hypertension or diabetes. However, certain migraine risk factors are not modifiable: being female, of low socioeconomic status, experiencing head trauma, and genetics.

In April, the American Academy of Neurology (AAN) and the American Headache Society issued new guidelines for the treatment of migraine that endorse preventive treatments using a wide variety of medications, from antidepressants to antihypertensives to plant extracts.

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. Physicians are encouraged to 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.