Can atogepant be a preventive treatment for cluster headache?-Insights from a case series

[Craigo]

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.

[CHfather]

In the US, the brand name for atogepant is Qulipta. In the EU, I think it's Aquipta.

@Craigo, thank you for this (and for all your other great contributions to substantive knowledge about CH)!  I notice that Ubrelvy and Nurtec are both also gepant formulations.  Might we imagine that they would also help (it seems from the abstract that the contrast in this study is with galcanezumab (Emgality))?  

 

[Tommy83]

Interesting, thanks for posting this. My Neuro has prescribed this for me at 60mg. I’ve not started just yet as I’ve been having some success with busting with 5-MeoDalt. Down to 1 attack per week and low pain shadows between. I was considering adding this layer on top. The cgrp blocker side effects of constipation and hair shedding give me the fear also :/ 

[Craigo]

On 10/10/2025 at 1:26 PM, CHfather said:

In the US, the brand name for atogepant is Qulipta. In the EU, I think it's Aquipta.

@Craigo, thank you for this (and for all your other great contributions to substantive knowledge about CH)!  I notice that Ubrelvy and Nurtec are both also gepant formulations.  Might we imagine that they would also help (it seems from the abstract that the contrast in this study is with galcanezumab (Emgality))?  

 

Hi CHfather - thanks for stopping in. This is the first case series I am aware of looking at a gepant and CH, in this case Qulipta / Atogepant. There is a trial looking at Nurtec / Rimegepant as a preventative therapy for CH. Ubrelvy / Ubrogepant is more an acute treatment owing to short half-life makes preventive use impractical and may not act quickly enough for acute CH attacks. I haven't read anything about the third generation gepant Zavegepant, again an acute treatment via nasal spray. I haven't really followed patient feedback on any them tbh.

I think this case series, if anything, may provide some context for clinicians considering where to next for refractory CH patients non-responsive to other treatments, including anti-CGRP mAbs like Emgality / Galcanezumab - this suggests that atogepant may be worth a try. I imagine there may be a tendency to think if a mAb hasn't previously worked or stopped working as was the case for one of the cases, a gepant is unlikely to either.

That being said, ya'll know I have had success with the vitamin D3 anti-inflammatory regimen and my personal view would be to exhaust the patient led treatments options that we have (busting + regimen) paired with abortives (oxygen and more recently DMT) before considering one of these new treatments because I am somewhat adverse to risk and there is no long term clinical data on their safety. For refractory patients for whom my heart truly aches, this may offer some hope - still, an early signal and a small case series.