Lasmiditan: New first-in-class drug treatment approved for migraine

Migraine is a huge medical problem, accounting for half of the disability produced by all neurologic diseases worldwide. The medication sumatriptan (Imitrex) is well known for the treatment of a migraine attack. Sumatriptan is part of a group of medications known as the triptans.

Triptan medications have been in use for over 20 years and are very effective for the acute treatment of headache (relieving migraine headaches that are already in progress). But they also have limitations; triptans can cause temporary narrowing of blood vessels in the heart and elsewhere that can result in side effects, such as chest pain or tightness or shortness of breath, which may at times be serious.

A medication that worked as well as a triptan, but without the same restrictions on use (for patients with prior heart attack, angina, or those with other vascular conditions) as the triptans, would be a welcome addition. Enter lasmiditan (Reyvow), which works without causing blood vessels to narrow.

How does lasmiditan work?

Lasmiditan is the first of a new group of headache medicines that are being called the “ditans.” Just like the triptans, lasmiditan can block a number of the processes that lead to the development of a full-blown headache. Taken at the first sign that a migraine is starting, it has the potential to stop the development of the headache and return the patient to normal function.

Clinical trials have shown a significantly greater number of patients being headache-free at two hours with lasmiditan compared to placebo. The main side effects noted in these studies were dizziness and sleepiness. These effects are probably related to the fact that this medication gets into and works inside the brain (triptans do not).

How lasmiditan works requires a bit of explanation. At one point in time, migraine was thought to result from abnormal dilation, or widening, of the blood vessels inside the head. A search for medications that could block this process, by producing blood vessel constriction (narrowing), led to the development of sumatriptan.

Sumatriptan was thought to be a blood vessel-constricting drug that targeted serotonin receptors (which are part of the pathway that triggers migraine pain) in the blood vessels and elsewhere, and blocked the development of headache. But it turned out that the headache benefit did not depend on blood vessel constriction. Surprisingly, the benefit was likely due to the triptan’s action at other serotonin receptors.

This led researchers to search for a medication that worked only at these other serotonin receptor sites, which could possibly block headache without causing vessel constriction. This search led to the development of lasmiditan.

Lasmiditan works on a specific type of serotonin receptor found not on blood vessels, but on nerves that are responsible for transmitting the pain of headache. These nerves are located both inside the brain itself, and inside the skull but outside of the brain. In testing, lasmiditan seems to block headache without having any effect on blood vessels.

FDA approves lasmiditan to treat migraine

The FDA recently approved lasmiditan and it should be available shortly in several dosages in pill form for treatment of a migraine attack. Lasmiditan should be used no more than once a day and no more than four times a month. Because of the possible side effects — dizziness and sleepiness — patients should not drive or perform other activities requiring mental alertness for eight hours after use. Animal studies suggest lasmiditan may not be safe in pregnancy, and thus should be avoided by women who are or may become pregnant.

Given the restrictions, this drug might be a choice for nonpregnant patients who cannot take triptans and want to treat a headache at the end of the day when going to bed anyway, or when the usual treatment of headache involves a period of sleep.

New drug represents greater understanding of headache

The development of lasmiditan represents increased scientific understanding of the problem of headache. As our knowledge develops, we can develop more specific and more effective treatments.

It is difficult to know at this point just where lasmiditan fits into the overall management of migraine. Whether we are on the verge of developing a whole new group of “ditan” medications will in part be determined by how well this first group member is accepted, and how useful it turns out to be in the real world.

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