Lasmiditan as the First and Only Representative of a New Class of Neuroactive Anti-Migraine Medications: A Review

INTRODUCTION. Lasmiditan, a new selective 5-HT_1F receptor agonist (approved by FDA in 2019), relieves migraine attacks via neuronal inhibition and acts in the central and peripheral nervous systems. Unlike triptans (5-HT _1B/1D receptor agonists), the major group of preparations used in severe migraines, lasmiditan does not cause vasoconstriction.

AIM. This study aimed to evaluate the role of lasmiditan, a representative of a new class of neuroactive anti-­migraine drugs (ditans), in migraine management based on its mechanism of action as well as effectivnes and safety review.

DISCUSSION. Anti-migraine mechanism of action of lasmiditan is due to its selective effect on 5-HT_1F serotonin receptors at the trigeminovascular level and in central nervous system pain-modulating pathways.

Lasmiditan demonstrated efficacy superior to placebo in three randomized clinical trials (SAMURAI, SPARTAN, CENTURION, n=5,910). In the population of patients with high cardiovascular risk, pain relief was achieved in 31.4% patients (100 mg) and 38.8% (200 mg) compared to 21.3% in the placebo group; the most bothersome symptom was reversed in 44.2% (100 mg) and 48.7% (200 mg) compared to 33.5% in the placebo group. The sustained pain relief was maintained in 13.6% and 17.3% of patients (100 and 200 mg, respectively).

Adverse events had the central character and were dose-dependent: dizziness (14.7%), paresthesia (5.7%), somnolence (5.5%), fatigue (3.8%), nausea (3.4%), muscle weakness (1.3%), and hypoesthesia (1.2%); no patient groups (including coronary disease) showed cardiovascular complications. Most adverse events were mild to moderate, while their incidence decreased with the long-term use of lasmiditan. There were rare reports of serotonin syndrome in randomized clinical trials and post-marketing experience. Impaired alertness and response rate was also observed for 8 h after lasmiditan intake.

CONCLUSIONS. Lasmiditan may serve as an alternative to triptans in patients at high cardiovascular risk or with poor response to triptans. The potential for central nervous system adverse events should be assessed, alongside with the potential neuropsychiatric complications, concomitant therapy, and occupational factors.

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