Journal of Human Biology and Clinical Medicine

Abstract

Primary headache disorders – migraine, tension-type headache, and cluster headache – represented one of the leading causes of years lived with disability worldwide, imposing a substantial socioeconomic burden across Europe, with annual costs estimated in billions of euros owing to lost productivity and increased healthcare utilisation. The aim of research was to critically evaluate evidence on pharmacological and non-pharmacological management of primary headache disorders published between 2019 and 2024, with a specific focus on European clinical data and guideline recommendations, in order to provide practitioners with an immediately applicable, evidence-based update. CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) demonstrated ≥ 50% responder rates of 40-60% and mean reductions of 3-8 monthly migraine days, with real-world European registry persistence exceeding 70% at 12 months – substantially outperforming traditional oral preventives. Oral gepants (atogepant for prevention; rimegepant for acute and preventive use) offered effective, cardiovascular-safe alternatives supported by both pivotal trials and European real-world cohorts. For cluster headache, high-flow oxygen (≥ 12 L/min) and subcutaneous sumatriptan 6 mg remained gold-standard acute treatments, while galcanezumab was the only biologic with strong evidence for episodic cluster headache prevention. Non-pharmacological interventions – cognitive behavioural therapy, biofeedback, structured aerobic exercise, and non-invasive vagus nerve stimulation – demonstrated moderate-to-high efficacy in reducing headache frequency and disability across all three disorders. Integrated multidisciplinary approaches combining pharmacological and behavioural strategies consistently showed superior long-term outcomes compared with monotherapy. European real-world data revealed meaningful improvements in quality of life, work productivity, and reductions in medication-overuse headache, confirming the applicability of guideline recommendations across diverse healthcare contexts. The findings provided neurologists, headache specialists, and primary care practitioners with a comprehensive, evidence-based synthesis of modern European management strategies, supporting a shift toward personalised, multidisciplinary headache care. Sustained implementation of European guidelines, harmonised cross-country access to novel therapies, and continued long-term safety monitoring remained essential priorities

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