Lasmiditan: New Migraine Drug in the Pipeline

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

A Novel Migraine Drug on the Horizon
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Migraines continue to remain a debilitating neurological condition—even with the introduction of triptans, which are medications traditionally used to abort a moderate-to-severe migraine attack.

The problem with triptans is that they simply do not always work for people—over 35 percent, according to scientific data. Also, people sometimes avoid them because of uncomfortable side effects, like chest tightness, throat and muscle pain, and numbness and tingling sensations.

So, is there an alternative to taking a triptan for a migraine? There may be one on the horizon and it's called lasmiditan. Like any drug, though, lasmiditan too may have some downsides that still need to be sorted out by researchers.

Still, learning about this novel anti-migraine drug is in your best interest as it may emerge as a viable option for you in the future. Additionally, if effective, lasmiditan may provide further insight into the biology behind migraine attacks. And, more specifically, it would support a neural theory of migraine origin as opposed to a vascular theory of migraine origin.

Is Lasmiditan Safe & Effective?

So far, there are two phase II trials of lasmiditan:

Study One

According to a randomized, placebo-controlled phase II study in Lancetlasmiditan appears to be effective for treating acute moderate-to-severe migraines. In this study, participants were randomized to receive either a placebo pill or a lasmiditan pill of varying doses (50mg, 100mg, 200mg, and 400mg).

Results revealed that every lasmiditan dose significantly improved headache response (defined as a reduction in moderate or severe migraine pain to mild or no pain) at two hours after headache onset, as compared to placebo.

While promising as an effective therapy, the downside of the drug may be its neurological-related side effects, which more participants experienced the higher the lasmiditan dose was.

These side effects included:

  • Dizziness

  • Fatigue

  • Vertigo (a sensation of spinning)

  • Paresthesia

  • Somnolence

Study Two

Another phase II study in Cephalalgia examined the intravenous (IV) administration of lasmiditan, which means it was given through a vein. The participants of the study had a moderate-to-severe migraine headache and they received either an IV dose of lasmiditan or a placebo dose in the hospital.

Results revealed that at a dose of lasmiditan 20mg IV, headache relief (defined again as a decrease in pain to mild or none at two hours) was 64 percent and for placebo it was 45 percent.

Adverse effects like dizziness, paresthesia, and a sensation of heaviness (usually a limb) were more common in the lasmiditan group than the placebo group (65 percent vs. 43 percent).

What Do These Two Studies Mean?

Both of these studies suggest that lasmiditan is an effective medication for treating acute migraines. Nevertheless, the studies do bring up tolerability issues regarding side effects. Larger phase III studies are needed to tease out these nervous system side effects as these could be limiting factors for future utilization.

How Lasmiditan Works

Similar to other migraine medications, the precise mechanism behind how lasmiditan works is not entirely clear.

That said, we know that it activates certain serotonin receptors in the brain—and in the brains of migraineurs, serotonin levels have been found to be decreased.

Triptans, the traditional medications used to treat moderate-to-severe migraines, also bind to serotonin receptors. So, how is lasmiditan unique from triptans? Experts note that lasmiditan is more selective than triptans—it does not bind to the serotonin receptors that, when activated, lead to blood vessel constriction (which triptans do).

In fact, this adverse effect (called vasoconstriction) is a big downside to triptans and is why they are contraindicated in people with a history of:

  • Heart disease
  • Stroke
  • Peripheral vascular disease
  • High blood pressure that is not controlled with medications
  • Certain types of migraines (for example, hemiplegic migraine and basilar migraine)

Furthermore, in animal studies, lasmiditan was found to block markers linked to electrical stimulation of the trigeminal ganglion. This fits in line with newer theories about the "why" behind migraine headaches, which is that pain is not a primary result of blood vessel widening surrounding the brain, but rather the activation of trigeminal nerve pathways.

So, lasmiditan presumes a more nerve-based cause of migraine pain as opposed to a vascular (blood vessel) cause. This may explain why triptans do not work for some migraineurs.

Other Innovative Therapies

It's still too early to say how lasmiditan will fare, but at least there are newer options emerging, and they are changing the way we understand how migraines develop. For instance, once the trigeminal system is activated during a migraine, substances like calcitonin gene-related peptide (CGRP) are released. These, in turn, widen blood vessels around the brain. Medications that block the protein CGRP either by binding to it directly or binding to its receptor are being developed, and early studies are promising.

In addition, and even more exciting are devices (not medications) that stimulate certain nerves, like the vagus nerve or the supraorbital nerve. These may be good choices for people who cannot take or tolerate current oral migraine drugs. However, they can be costly and insurance coverage can be an issue.

A Word From Verywell

Overall, the big picture here is that lasmiditan seemed to be effective in two phase II studies for soothing migraine pain. But, it's important to remember that larger studies are needed (phase III studies) to tease out the nervous system side effects as these could be limiting factors for some people. The good news is that there are enrolling or ongoing phase III studies at this time.

Sources:

Aggarwal M, Puri V, Puri S. Serotonin and CGRP in Migraine. Ann Neurosci. 2012 Apr;19(2):88-94.

Capi M et al. Lasmiditan for the treatment of migraine. Expert Opin Investig Drugs. 2017 Feb;26(2):227-34.

Farkkila M et al. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol. 2012 May;11(5):405-13.

Ferrari MD et al. Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomized proof-of-concept trial. Cephalalgia. 2010 Oct;30(10):1170-8.

Peer C Tfelt-Hansen, Olesen J. The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials. J Headache Pain. 2012 Jun;13(4):271-75.

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