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Can atogepant be a preventive treatment for cluster headache?-Insights from a case series Catarina Serrão, Filipa Dourado Sotero, Linda Azevedo Kaupilla, Isabel Pavão Martins Published in Headache on October 3, 2025 Link: https://doi.org/10.1111/head.15066 Abstract: Cluster headache (CH) is a disabling primary headache disorder with limited therapeutic options. Calcitonin gene-related peptide (CGRP) is known to be involved in CH pathophysiology; however, except for galcanezumab (300 mg) in episodic CH, anti-CGRP monoclonal antibodies did not reduce CH attacks in randomized clinical trials. Atogepant is an oral, small-molecule, CGRP receptor antagonist, which is approved for the preventive treatment of migraine. Here, we describe four case reports of CH (two episodic CH and two chronic CH), unresponsive to previous prophylactic treatments, who responded to daily atogepant (60 mg). Chronic CH cases were refractory to subcutaneous galcanezumab. In one case, a reduction to atogepant (30 mg daily) resulted in recurrence of headache attacks, which subsided on reintroduction of the initial dose. No serious adverse effects were reported. Despite the limited number of cases and the open retrospective design, our case series suggests atogepant as a possible prophylactic treatment for CH. Further research on CGRP signaling in CH and the implementation of well-designed clinical trials are necessary.

We have such an amazing community and it's hard to just pick a few people, so for our 20th we picked a few extra But seriously we have the best community- just wanted to give a shout out to these amazing people!

The recording is on our YouTube channel if you'd like to watch.

PACAP-38 in Cluster Headache: A Prospective, Case–Control Study of a Potential Treatment Target Marie-Louise K. Søborg, Nunu Lund, Agneta Snoer, Mads Barloese, Rigmor Højland Jensen, Anja Sofie Petersen Published in European Journal of Neurology on September 26, 2025 Link: https://doi.org/10.1111/ene.70341 Abstract: (partial selection) This large-scale study demonstrated increased PACAP-38 levels in all disease states of cluster headache compared to headache-free controls, strengthening the hope of a possible effect of PACAP-38 targeting treatments in future trials. The lacking correlation between PACAP-38 and CGRP levels should be interpreted with caution and needs to be investigated in future studies.

Here is a screenshot from one of the authors posts on LinkedIn. The research coming out of the Danish Headache Center is outstanding, I have recently shared the findings of their paper identifying the distinct cytokine profiles that distinguish eCH from cCH and also found that Oncostatin M was elevated in all 3 CH states.