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. 2025 Feb;14(1):237-255.
doi: 10.1007/s40122-024-00675-6. Epub 2024 Nov 9.

Safety of Rimegepant in Adults with Migraine and Anxiety, Depression, or Using Antidepressants: Analysis of a Multicenter, Long-Term, Open-Label Study

David Kudrow  1 , Susan Hutchinson  2 , Glenn C Pixton  3 , Terence Fullerton  3
Affiliations

Safety of Rimegepant in Adults with Migraine and Anxiety, Depression, or Using Antidepressants: Analysis of a Multicenter, Long-Term, Open-Label Study

David Kudrow et al. Pain Ther. 2025 Feb.

Abstract

Introduction: Anxiety and depression are frequently associated with migraine, and antidepressant use can complicate treatment. These analyses assessed the safety and tolerability of rimegepant in participants with migraine and anxiety and/or depression, or using selective serotonin reuptake inhibitors (SSRIs) and/or other antidepressants.

Methods: Data were from a phase II/III safety study of rimegepant for the acute treatment of migraine. Participants with a history of 2-14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg as needed up to once daily for up to 52 weeks. These post hoc subgroup analyses assessed safety according to self-reported history of anxiety (yes or no) or depression (yes or no), and current use of SSRIs (yes or no) or other antidepressants (yes or no).

Results: Of 1800 treated participants, 23.2% (n = 417) had a self-reported history of anxiety, 23.7% (n = 426) had a self-reported history of depression, and 11.2% (n = 202) reported both anxiety and depression. A total of 10.1% (n = 181) of participants were using an SSRI, 10.8% (n = 195) were using other antidepressants, and 1.8% (n = 32) were using both. Across the subgroups with anxiety, without anxiety, with depression, without depression, using SSRIs, not using SSRIs, using other antidepressants, and not using other antidepressants, respectively, similar proportions of participants reported adverse events (67.1%, 58.4%, 62.0%, 60.0%, 64.1%, 60.0%, 66.2%, 59.8%), serious adverse events (3.6%, 2.3%, 2.8%, 2.5%, 3.3%, 2.5%, 5.1%, 2.3%), and discontinuation of rimegepant due to adverse events (4.1%, 2.2%, 3.1%, 2.5%, 5.0%, 2.4%, 3.1%, 2.6%). Numerical improvements in a variety of participant-reported outcomes were also observed at weeks 12 and 52.

Conclusions: Rimegepant showed favorable safety and tolerability in adults with migraine and a history of anxiety and/or depression and with SSRI and/or other antidepressant use.

Trial registration: Clinicaltrials.gov: NCT03266588.

Keywords: Anxiety; Calcitonin gene-related peptide receptor antagonist; Depression; Mental health; Migraine; Rimegepant.

Plain language summary

People with migraine often have anxiety and depression, and the use of antidepressants can complicate the choice of migraine treatment. These analyses of a long-term, open-label, phase II/III study assessed the safety and tolerability of rimegepant in adults with migraine according to history of anxiety and/or depression, and the use of antidepressants. Rimegepant, when used as an acute treatment for migraine, was generally safe and well tolerated in adults with migraine and a history of anxiety and/or depression, and with antidepressant use.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. David Kudrow reports research grants from Pfizer, Lilly, Aeon, AbbVie, and Biohaven; speakers bureau for AbbVie; and serving on advisory boards for Lundbeck and AbbVie. Susan Hutchinson has served as a consultant for AbbVie, Astellas, Biohaven, Impel, Lilly, Lundbeck Teva, Theranica, and Upsher-Smith. She is on the speakers bureau for AbbVie, Astellas, Impel, Lilly, and Lundbeck. Glenn C. Pixton is an employee of Pfizer and owns stock/stock options in Pfizer, and owns stock in AbbVie. Terence Fullerton is an employee of Pfizer and owns stock/stock options in Pfizer. Ethical Approval: The study was conducted in accordance with Good Clinical Practice, as defined by the International Conference on Harmonisation, Good Laboratory Practice, the Declaration of Helsinki, and all applicable regulations. Prior to the study, all participants provided written informed consent, and the protocol received Institutional Review Board approval (Advarra IRB [IRB00000971], Schulman Associates IRB [IRB00007642; acquired by Advarra], and Biomedical Research Alliance New York [BRANY] IRB [IRB00000080]).

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