The migraine postdrome: Spontaneous and triggered phenotypes.

BACKGROUND: Non-painful symptoms in migraine following headache resolution can last up to days. Studying the postdrome is important to appreciate the morbidity associated with migraine. METHODS: Fifty-three subjects (n = 53) with migraine were studied in an experimental setting, collecting historical phenotypic information on the postdrome in their spontaneous attacks, and also associated with nitroglycerin-triggered attacks, while being observed prospectively. In a separate headache clinic-based cohort of migraineurs (n = 42), who were age and sex-matched to the experimental group, the same phenotypic data were extracted from their clinic records. Spontaneous and nitroglycerin-triggered attack phenotypes, and experimental and clinical cohort phenotypes were compared using agreement analysis. RESULTS: In the experimental group, 100% had a postdrome with their triggered attack, while 98% reported a postdrome in their spontaneous attacks. In the clinical group, 79% had reported a postdrome. In the experimental group, there was good agreement between spontaneous and nitroglycerin-triggered tiredness, hunger, mood change, sensory sensitivities and vertigo and with similarity in premonitory and postdrome phenotypes experienced in the same individual. CONCLUSIONS: The migraine postdrome is common and symptomatically similar to the premonitory phase. The nitroglycerin model and migraine abortive agents can be used to study the postdrome experimentally. Systematic questioning of symptoms, as well as collateral histories from direct observers of migraine attacks, are likely to enhance symptomatic capture of the migraine postdrome, and aid understanding of attack mediation, abortion and neurobiology.

Gepants, calcitonin-gene-related peptide receptor antagonists: what could be their role in migraine treatment?

PURPOSE OF REVIEW: Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug-drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients. RECENT FINDINGS: After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials. SUMMARY: Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest efficacy. Atogepant has shown efficacy in migraine prevention in a phase II/III study. Most importantly, hepatotoxicity has not been reported in specifically designed phase I studies or long-term extension studies, with rimegepant or ubrogepant, or in a preventive study with atogepant. Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. Because of the particular benefit gepants may represent for these groups of patients, specific studies in patients with medication overuse headache, as well as those with comorbid cardiovascular diseases, would be of considerable interest.