The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse

• Published in: Journal of headache and pain Vol. 20; no. 1; pp. 54 - 7
• Main Authors: van Hoogstraten, Willem Sebastiaan, MaassenVanDenBrink, Antoinette
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 16-05-2019; Springer Nature B.V; BMC
• Subjects: Acute antimigraine drugs; Agonists; Animal models; Animals; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide Receptor Antagonists - adverse effects; Calcitonin Gene-Related Peptide Receptor Antagonists - pharmacology; Calcitonin Gene-Related Peptide Receptor Antagonists - therapeutic use; Cerebral cortex; Chronic migraine; Cortical spreading depression; Drugs; Gepants; Headache; Headache Disorders, Secondary - chemically induced; Headache Disorders, Secondary - prevention & control; Humans; Internal Medicine; Medication overuse headache; Medicine; Medicine & Public Health; Migraine; Migraine Disorders - drug therapy; Neurology; Pain Medicine; Prescription Drug Overuse - prevention & control; Review; Review Article; Serotonin Receptor Agonists - adverse effects; Serotonin Receptor Agonists - pharmacology; Serotonin Receptor Agonists - therapeutic use; Serotonin S1 receptors; Serotonin S2 receptors; The changing face of migraine; Triptans; Chronic migraine; Ditans; Triptans; Gepants; Migraine; Medication overuse headache; Acute antimigraine drugs; Lasmiditan
• ISSN: 1129-2369; 1129-2377
• DOI: 10.1186/s10194-019-1007-y

Background
The treatment of migraine is impeded by several difficulties, among which insufficient headache relief, side effects, and risk for developing medication overuse headache (MOH). Thus, new acutely acting antimigraine drugs are currently being developed, among which the small molecule CGRP receptor antagonists, gepants, and the 5-HT
1F
receptor agonist lasmiditan. Whether treatment with these drugs carries the same risk for developing MOH is currently unknown.
Main body
Pathophysiological studies on MOH in animal models have suggested that decreased 5-hydroxytryptamine (5-HT, serotonin) levels, increased calcitonin-gene related peptide (CGRP) expression and changes in 5-HT receptor expression (lower 5-HT
1B/D
and higher 5-HT
2A
expression) may be involved in MOH. The decreased 5-HT may increase cortical spreading depression frequency and induce central sensitization in the cerebral cortex and caudal nucleus of the trigeminal tract. Additionally, low concentrations of 5-HT, a feature often observed in MOH patients, could increase CGRP expression. This provides a possible link between the pathways of 5-HT and CGRP, targets of lasmiditan and gepants, respectively. Since lasmiditan is a 5-HT
1F
receptor agonist and gepants are CGRP receptor antagonists, they could have different risks for developing MOH because of the different (over) compensation mechanisms following prolonged agonist versus antagonist treatment.
Conclusion
The acute treatment of migraine will certainly improve with the advent of two novel classes of drugs, i.e., the 5-HT
1F
receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants). Data on the effects of 5-HT
1F
receptor agonism in relation to MOH, as well as the effects of chronic CGRP receptor blockade, are awaited with interest.