Emerging Pharmacological Therapies for Paediatric Migraine: From Conventional Treatments to CGRP-Targeted Therapie

Abstract

Paediatric migraine is a prevalent and disabling neurovascular disorder that substantially impairs academic performance, psychosocial development, and quality of life in children and adolescents. Despite its significant global burden, pharmacological management remains limited by sparse paediatric-specific evidence, high placebo response rates in clinical trials, and reliance on extrapolated adult data. Conventional acute therapies, including non-steroidal anti-inflammatory drugs and triptans, remain the cornerstone of symptomatic management, whereas preventive agents such as topiramate, amitriptyline, propranolol, and flunarizine demonstrate variable efficacy and are frequently constrained by tolerability concerns. The landmark Childhood and Adolescent Migraine Prevention (CHAMP) trial further challenged the effectiveness of traditional preventive therapies by demonstrating no superiority of amitriptyline or topiramate over placebo. Recent advances in migraine neurobiology have identified calcitonin gene-related peptide (CGRP) as a pivotal mediator in trigeminovascular activation and migraine pathophysiology, leading to the development of mechanism-based CGRP-targeted therapies. Anti-CGRP monoclonal antibodies, including erenumab, fremanezumab, galcanezumab, and eptinezumab, together with small-molecule CGRP receptor antagonists (gepants), represent a transformative therapeutic paradigm with improved specificity and favourable tolerability profiles. Emerging paediatric trials such as REBUILD, SPACE, and HEADWAY have provided encouraging preliminary evidence regarding efficacy, pharmacokinetics, and safety in adolescents and children, although long-term developmental 
safety data remain limited. This review critically examines current pharmacological strategies for paediatric migraine, comparing conventional therapies with emerging CGRP-targeted agents in terms of mechanisms, efficacy, safety, and clinical applicability. Particular emphasis is placed on developmental neurobiology, paediatric pharmacokinetic considerations, methodological limitations of paediatric migraine trials, and future directions in precision-based headache therapeutics. CGRP-targeted therapies hold substantial promise for addressing the unmet therapeutic needs of paediatric migraine; however, rigorous long-term paediatric studies and structured 
pharmacovigilance remain essential before widespread clinical integration.