Migraine is an important socioeconomic burden and is ranked the sixth cause of years of life lost because of disability in the general population and the third cause of years of life lost in people younger than 50 years. The cornerstone of pharmacological treatment is represented by the acute
therapy. The
serotonin (
5-hydroxytryptamine [
5-HT]) receptor subtype 1B/1D agonists, called
triptans, are nowadays the first-line acute
therapy for patients who experience moderate-to-severe
migraine attacks. Unfortunately, a high percentage of patients are not satisfied with this acute treatment, either for lack of response or side effects. Moreover, their mechanism of action based on vasoconstriction makes them unsuitable for patients with previous cardio- and
cerebrovascular diseases and for those with uncontrolled
hypertension. Since the introduction of
triptans, no other acute
drug class has passed all developmental stages. The research for a new
drug lacking vasoconstrictive effects led to the development of
lasmiditan, a highly selective
5-HT1F receptor agonist with minimized interactions with other
5-HT receptor subtypes.
Lasmiditan is considered to be the first member of a new
drug category, the neurally acting anti-
migraine agent (
NAAMA). Phase II and III trials had shown superiority compared to placebo and absence of typical
triptan-associated adverse events (AEs). Most of the AEs were related to the central nervous system, depending on the high permeability through the blood-brain barrier and mild to moderate severity. The results of ongoing long-term Phase III trials will determine whether
lasmiditan will become available in the market, and then active
triptan comparator studies will assess patients' preference. Future studies could then explore the safety during pregnancy and breastfeeding or the risk that overuse of
lasmiditan leads to
medication overuse headache.