CGRP-Blocking Drug Rimegepant Prevented Menstrual Migraines in 85% of Cycles | Research

The takeaway

Taking rimegepant every other day around menstruation prevented perimenstrual migraine attacks in 85% of cycles, though 60% of patients experienced migraines displaced to days after treatment stopped.

85% of cycles protected
Rimegepant prevented anticipated perimenstrual migraine attacks in 17 of 20 treatment cycles, though temporal displacement occurred in 60% of patients

What the researchers found

Rimegepant 75 mg taken every other day during the perimenstrual window prevented anticipated migraine attacks in 17 out of 20 treatment cycles (85%), with no adverse events reported. However, the picture was more nuanced: only one patient (20%) achieved a sustained reduction in total monthly migraine days. Three patients (60%) experienced a 'temporal displacement' phenomenon, where migraine attacks that were prevented during the perimenstrual window reappeared 3–7 days after menstruation ended.

All five patients reported high satisfaction with perimenstrual symptom control despite the displacement effect, suggesting that even shifting migraines away from the most symptomatic period provided meaningful clinical benefit.

Why it matters

Menstrual migraines are among the most debilitating and treatment-resistant migraine subtypes. Traditional short-term prevention with NSAIDs or triptans often fails or is contraindicated. Rimegepant, which targets the CGRP peptide pathway central to migraine pathophysiology, offers a targeted approach. The 'temporal displacement' finding is particularly important — it suggests that CGRP blockade alone may not address the underlying hormonal trigger, pointing to complex interactions between estrogen withdrawal and peptide signaling in migraine.

How the study worked

This hypothesis-generating case series enrolled five women aged 22–42 with episodic migraine and regular menstrual cycles. Each received rimegepant 75 mg orally disintegrating tablet every other day, starting two days before menstruation and continuing until two days post-menstruation. Patients maintained daily headache diaries recording migraine days, severity, and treatment use. Outcomes included perimenstrual migraine day reduction, overall monthly migraine frequency, tolerability, and adverse events. Follow-up was conducted after 3–4 treatment cycles.

What this study cannot tell us

This is a very small case series of only five patients with no control group, blinding, or randomization. The 85% prevention rate may overestimate effectiveness due to the small sample and potential placebo effect. The temporal displacement observation, while intriguing, could also reflect natural migraine variability. The every-other-day dosing schedule was not compared to daily dosing or other regimens. These preliminary findings require confirmation in randomized controlled trials.

How to read the evidence

This is a very small case series (5 patients, 20 cycles) with no control group, representing the lowest tier of clinical evidence. While the results are promising and hypothesis-generating, they cannot establish efficacy. The authors appropriately call for randomized controlled trials to confirm these preliminary findings.

When this study was published

Published in 2025, this is a very recent case series exploring a novel application of rimegepant that is at the early investigational stage.

The bigger picture

CGRP-targeting therapies have revolutionized migraine treatment over the past decade, including both monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small-molecule antagonists (rimegepant, ubrogepant). This study explores a novel use pattern — intermittent short-term prevention timed to the hormonal trigger — which could expand how these peptide-pathway drugs are deployed. The temporal displacement phenomenon also adds scientific insight into the relationship between CGRP signaling and hormonal migraine mechanisms.

Questions still open

Would daily rimegepant dosing during the perimenstrual window prevent the temporal displacement of migraines seen with every-other-day dosing?
What role do hormonal mechanisms independent of CGRP play in driving delayed migraine attacks after the treatment window?
Could combining rimegepant with hormonal stabilization strategies eliminate both perimenstrual and displaced migraines?

Common questions

What is CGRP and why does blocking it help with migraines?

CGRP (calcitonin gene-related peptide) is a 37-amino-acid peptide released by nerve cells during migraine attacks. It causes blood vessels in the brain to dilate and triggers inflammation and pain signaling. Drugs like rimegepant block the CGRP receptor, preventing the peptide from initiating the cascade of events that produces migraine pain. CGRP levels rise during menstruation due to estrogen withdrawal, which is why menstrual migraines are particularly linked to this peptide pathway.

What is 'temporal displacement' of migraines and what does it mean?

In this study, three of five women who were successfully protected from migraines during their perimenstrual window experienced migraine attacks 3–7 days after menstruation ended — when they would not normally have had them. This 'temporal displacement' suggests that rimegepant suppressed the CGRP-mediated trigger during treatment but didn't address the underlying hormonal cascade, which may have 'stored up' and triggered a delayed attack once the drug was stopped. This finding points to migraine biology being more complex than CGRP signaling alone.

Read the original research

Short-term prevention of perimenstrual migraine with rimegepant.

The journal of headache and pain, 26(1), 253

View on PubMed ↗Publisher’s paper ↗

Citation

Frank, Florian; Schiefecker, Alois; Kaltseis, Katharina; Eller, Michael; Broessner, Gregor. (2025). Short-term prevention of perimenstrual migraine with rimegepant.. The journal of headache and pain, 26(1), 253. https://doi.org/10.1186/s10194-025-02185-y