Lasmiditan: A New Migraine Drug in the Pipeline

An alternative to triptans, but the side effects may be limiting

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Lasmiditan is an investigational migraine medication currently being developed by Eli Lilly, a pharmaceutical manufacturer. Eli Lilly submitted a new drug application (NDA) for lasmiditan to the United States Food and Drug Administration (FDA) in November 2018. This is the first step in applying for its approval.

A phase lll trial of this medication is underway, and the results of two earlier phase III trials which have already been released suggest that lasmiditan may be safe and effective as a treatment for acute migraine attacks.

How It Works

Lasmiditan activates certain 5-HT (serotonin) receptors in the brain. Serotonin is a neurotransmitter that modulates pain and mood, and also induces vasoconstriction (narrowing of the blood vessels).

It has long been known that vasodilation (widening of blood vessels) may play a role in migraines and that some medications used for migraines, like triptans and dihydroergotamines (DHE), induce vasoconstriction. But it is not clear whether vasodilation is the cause of migraines or whether it occurs as the result of an even earlier migraine process, such as a disruption of electrical activity in the brain.

Lasmiditan does not induce vasoconstriction. Instead, it has been suggested that lasmiditan may act on electrical pathways in the brain to alleviate migraines. This is a different mechanism of action than other migraine medications, making lasmiditan unique.

Eli Lilly describes lasmiditan as a selective serotonin 5-HT1F agonist, which means that it does not activate all 5-HT receptors and instead only selects for the 5-HT1F receptors. This subset of 5-HT receptors does not induce vasoconstriction.

Potential Advantage

Many of the potent and effective migraine medications that induce vasoconstriction, including triptans, ergotamines, and DHE, are not safe if you have cardiovascular risk factors, such as heart disease, vascular disease, or history or risk of stroke.

Because lasmiditan is a selective 5-HT agonist that does not induce vasoconstriction, researchers suggest that it may be safe for people who have cardiovascular disease. In fact, 77.9 percent of the participants in the SAMURAI trial had at least one cardiovascular risk factor.

The Research

This medication is not intended to be used as a preventative or prophylactic migraine therapy, and it has only been investigated for migraines, not for other conditions or headache types.

Data from the completed phase lll clinical research trials, called SAMURAI and SPARTAN, showed that lasmiditan was more effective than placebo (non-active compound) for treatment of acute migraine attacks.

A publication in the journal Neurology reported that 40.7 percent of the participants in the SAMURAI trial experienced significant improvement of their most bothersome migraine symptom two hours after their first 200 mg dose of lasmiditan (compared to 29.5 percent with placebo). Additionally, 32.2 percent of the participants were migraine-free two hours after their first 200 mg dose of lasmiditan, and 28.2 percent were migraine-free two hours after their first 100 mg dose of the drug (compared to 15.3 percent with placebo).

In the SPARTAN trial, 48.7 percent of participants experienced significant improvement of their most bothersome migraine symptom two hours after their first 200 mg lasmiditan dose (compared to 33.5 percent with placebo), and 38.8 percent were migraine-free two hours after their first 200 mg dose of the drug (compared to 21.3 percent with placebo).

The most bothersome migraine symptoms reported by the participants included photophobia (sensitivity to light), nausea, and phonophobia (sensitivity to sound).

Side Effects

The side effects of lasmiditan have been reported to be mild to moderate.

A phase ll study published in Lancet found a dose-related side effect response, which means that higher doses were associated with more side effects.

Side effects associated with lasmiditan include:

  • Dizziness
  • Nausea
  • Fatigue
  • Numbness
  • Muscle weakness
  • Paresthesia
  • Somnolence (sleepiness and tiredness)

Interactions and Contraindications

Given that lasmiditan is still in the study phase, contraindications and drug interactions have not been formally established. If you are going to enter a clinical trial with possible exposure to lasmiditan, then the study directors may have exclusions for some medications or medical conditions.

If lasmiditan becomes FDA-approved, then a list of drug interactions and contraindications will be established and published, and your doctor and pharmacist can advise you regarding any safety issues.

A Word From Verywell

Migraines are among the most common recurrent conditions, and not everyone improves with the same treatment.

The good news is that new migraine medications may be on the horizon. As new migraine medications become available, your chances of finding the best fit for treating your acute episodes— with minimal to no side effects— is bound to increase.

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