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

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.