Current Series: Chronic Migraine: New Paradigms in Management

Stephen Silberstein, MD: I treat migraine early because it works better. Why does it work better? The longer a migraine attack persists, the more the brain becomes excited and the nerves inside the brain become excited. And triptans only work early in the course before we have this phenomenon of central sensitization. Treat early and get a better result.

When does one use preventative medications for the treatment of migraine? (1) When acute medicine doesn’t work, is overused, or not tolerated; (2) Patient preference: If you’re a neurosurgeon, you don’t want to get a migraine attack; (3) The presence of 4 migraine attacks a month, which is a risk factor for chronic migraine. The presence of unusual or disabling attacks that don’t come under control with acute medicine. That’s when patients need prevention.

Most of the drugs that we have to treat patients with migraine have been devised by accident. A patient had angina or hypertension, they got a beta-blocker, and it worked for migraine. So the older drugs that we use, like beta-blockers and antidepressants, were based on their use in other disorders. With the antiepileptic drugs, patients with epilepsy might have migraine, and their headaches got better. So based on the fact that patients getting these drugs in other indications got better, trials were set up and they’re now approved. So that’s how the older drugs were developed. Now, we know a lot about the mechanism of migraine. We know about CGRP. Based on that concept, we’ve developed small molecules of antibodies against CGRP for the preventative treatment of migraine.

During a migraine attack, CGRP levels go up. If the migraine attack is treated with a migraine-specific medicine like sumatriptan, the levels go down. If you infuse CGRP in a patient with migraine, that can bring on a migraine attack. This strongly suggests that CGRP was involved in the cause of a migraine attack. Based on that, drugs that antagonize CGRP were developed.

This is an exciting time in migraine. The FDA has approved 3 monoclonal antibodies for the preventative treatment of migraine. The first was against the CGRP receptor. The second 2 were against CGRP itself. Awaiting FDA approval is another drug in the antibody class against CGRP itself, and that will hopefully occur soon.