Migraines are the most common type of primary headache disorders, and triptans – serotonin 5-HT1B/1D receptor agonists originally developed as cranial vasoconstrictors – are the backbone of current acute attack treatment. Additional standard therapies include non-steroidal anti-inflammatory drugs, acetaminophen, anti-emetics, corticosteroids and opioids.1 Prof. Peter Goadsby presented the latest advances in migraine therapy at the ‘Hot Topics in Headaches and Related Disorders II: Migraine Pathophysiology, Brain Imaging and Therapeutic Advances’ session at the 2019 AAN Annual Meeting.2
Triptans most likely act through 5-HT1D receptor-mediated neural transmission, and their vasoconstrictor properties seem to be independent of their mode of action.1 Vascular effects of triptans are 5-HT1B receptor-mediated, and render this therapy unsafe for patients with cardiovascular and/or cerebrovascular disorders.3 A new class of therapeutics addresses this limitation of triptans – “ditans” are serotonin 5-HT1F receptor-selective agonists.3 Lasmiditan, currently in phase I/II clinical trial investigation, has shown no vasoconstrictive effects in preclinical trials. While its efficacy and safety still need to be demonstrated, lasmiditan might offer an alternative for acute migraine treatment without associated cardiovascular risks.3
Calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide in migraine pathophysiology – activation and sensitisation of the trigeminovascular system is known to be painful and its stimulation leads to increased CGRP levels. Small-molecule antagonists of the CGRP receptor, gepants, are currently in development for migraine therapy.4 Prof. Goadsby presented clinical trial data demonstrating the efficacy and safety of gepants for acute migraine treatment. However, liver toxicity has been associated with some gepant molecules, suggesting an intermittent, rather than daily, use for selected members of this new class of migraine therapeutics. In addition to gepants, monoclonal antibodies targeting CGRP or the CGRP receptor are currently in development and have shown encouraging results in clinical trials, particularly a favourable safety profile. Prof. Goadsby proceeded with an overview of non-invasive neuromodulation techniques, namely single-pulse transcranial magnetic stimulation (sTMS) and non-invasive vagal nerve stimulation (nVNS).
Prof. Goadsby highlighted that while prophylaxis is preferred over treatment, most available prophylactic therapeutics have been developed for other indications, limiting their efficacy and safety for migraine treatment. Prof. Goadsby ended his presentation with a call to action to all young researchers to tackle the numerous challenges remaining the field of migraines.
- PJ Goadsby and PR Holland. Migraine Therapy: Current Approaches and New Horizons. Neurotherapeutics. 2018;15:271–3.
- PJ Goadsby. “Hot Topics in Headaches and Related Disorders II: Migraine Pathophysiology, Brain Imaging and Therapeutic Advances”. Presented at AAN Annual Meeting, 4–10 May, 2019.
- M Vila-Pueyo. Targeted 5-HT1F Therapies for Migraine. Neurotherapeutics. 2018;15:291–303.
- PR Holland and PJ Goadsby. Targeted CGRP Small Molecule Antagonists for Acute Migraine Therapy. Neurotherapeutics. 2018;15:304–12.