Injection-Based Therapies for Migraine in Older Adults: A Narrative Review of OnabotulinumtoxinA, Greater Occipital Nerve Block, and Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies

Abstract

As global populations age, the clinical approach to managing migraine must evolve. Migraine in older adults presents unique treatment challenges due to comorbidities, poor adherence to treatment, altered pharmacokinetics, and polypharmacy. Injection -based preventive treatments such as onabotulinumtoxinA (BoNT-A), greater occipital nerve blocks (GONB), and anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) offer promising alternatives. This narrative review highlights the underrepresentation of older adults in migraine clinical trials and summarizes the effectiveness and safety of BoNT-A, GONB, and CGRP mAbs in patients over 65 years of age. To identify relevant studies addressing migraine management in the older adults, we conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library. The search was limited from the past ten years, up to 5 April 2025. Studies were included if clinical trial, observational, real-world data, or review examined migraine treatment in adults over 65 years, with separate data according to age. A total of 22 studies were included: 4 on BoNT-A, 2 on GONB, 13 on anti-CGRP mAbs, and 3 reviews on injectable therapies. BoNT-A has shown significant benefits in reducing migraine frequency, acute medication use, and disability in real-world settings though randomized trials did not include older adults. GONB has demonstrated high response rates in older adults, although there was no separate analysis for patients over 65 years of age in randomized controlled trials. In contrast, CGRP mAbs have increasingly included in trials, with some trials enrolling patients up to 75 years. Subgroup analyses and real-world data support their comparable effectiveness and safety in older adults. BoNT-A, GONB and CGRP mAbs show effectiveness and are well tolerated for migraine prevention in older adults. Given the growing ageing population and their unique therapeutic needs, proactive migraine management in older migraine patients with injection-based and oral preventive is essential.