Optimizing Migraine Therapy: A Comparative Review of Dosage and Tolerability of Calcitonin Gene Related Peptide Antagonists

Sarabjot Singh-Sethi-Makkar

University of California Irvine, California, USA.

Parinita Aroori *

Kalinga Institute of Medical Sciences, Bhubaneswar, India.

Leela Sarmada Gaddamanugu

Mysore Medical College and Research Institute, Mysore, India.

Siddharth Thokale

Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India.

Krishna Moparthi

John F. Kennedy University School of Medicine, Willemstad, Curaçao.

Kyaw Hein

HCA Mountain View, Las Vegas, USA.

Sanjana Palakodeti

Kamineni Institute of Medical Sciences, Telangana, India.

*Author to whom correspondence should be addressed.


Abstract

Background: Migraines are a common neurological disorder which are characterised by recurrent headaches accompanied by ‘auras’, nausea, vomiting and photophobia.

Objective: This review summarises the role of Calcitonin gene-related peptide (CGRP) in migraine as a therapeutic and prophylactic target and evaluates the dosage strategies and tolerability of CGRP inhibitors. 

Summary of Findings: CGRP is a central mediator of migraines and its inhibition is led by two major classes of therapies: the monoclonal antibodies (mAbs) and small-molecule receptor antagonists (gepants). The mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) are usually administered monthly/quarterly for prophylaxis and reduce overall monthly migraine days with favourable tolerability (mild injection site reactions seen). On the other hand, gepants (ubrogepant, rimegepant, atogepant, zavegepant) are available for use in oral and nasal formulations for both therapeutic and prophylactic use. They show moderate tolerability with acceptable gastrointestinal or neurological adverse effects. Collectively, CGRP-targeted therapies expand treatment options, offering flexibility in route, frequency, and clinical application.

Conclusion: CGRP inhibitors are a relatively new therapy which are well tolerated and effective treatments that can be individualised to each patient’s needs. Further ongoing studies are required for establishing long term safety, durability and efficacy.

Keywords: Migraine, calcitonin gene–related peptide, monoclonal antibodies, gepants, dosage, adverse effects


How to Cite

Singh-Sethi-Makkar, Sarabjot, Parinita Aroori, Leela Sarmada Gaddamanugu, Siddharth Thokale, Krishna Moparthi, Kyaw Hein, and Sanjana Palakodeti. 2025. “Optimizing Migraine Therapy: A Comparative Review of Dosage and Tolerability of Calcitonin Gene Related Peptide Antagonists”. Journal of Pharmaceutical Research International 37 (9):57-65. https://doi.org/10.9734/jpri/2025/v37i97742.

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