Medication overuse headache: from brain alterations to disease burden

Reyes-Alvarez M.T.; Gudiño-Castelazo M.; Figueroa-Medina M.J.; Gonzalez M.V.; Saavedra-Rocha C.A.; Miranda S.M.; Morales-Morales M.A.; Dominguez-Moreno R.; Contreras-Martinez M.A.; Krymchantowski A.V.; Láinez J.M. · Headache Medicine (2025) · DOI: 10.48208/headachemed.2025.36

Resumen

Introduction Medication-overuse headache is a secondary headache that develops in patients with a pre-existing primary headache, most often migraine, who experience daily or near-daily headaches as a result of excessive intake of symptomatic medications. According to the ICHD-3 criteria, diagnosis requires ≥15 headache days per month and ≥10–15 days per month of medication use, depending on the drug class, for at least three months. Objective To review the pathophysiological mechanisms, risk factors, clinical impact, and regional characteristics, highlighting therapeutic implications and current research gaps. Methods A narrative review of recent high-quality literature indexed in PubMed was conducted, integrating clinical, epidemiological, and experimental data, to ensure comprehensive coverage of emerging evidence. Results Pathophysiology involves dysregulation of the trigeminovascular system, cortical hyperexcitability, maladaptive neuroplasticity, and dysfunction of dopaminergic reward circuits, showing parallels with addictive disorders. Major risk factors include female sex, high baseline headache frequency, psychiatric comorbidities, socioeconomic vulnerability, and genetic predisposition. Alterations in CGRP and endocannabinoid systems may further increase susceptibility. In Latin America, ergotamine remains the most frequently overused drug, unlike triptans and simple analgesics in developed countries, underscoring regional disparities and safety concerns. Conclusion Medication-overuse headache is a preventable yet underdiagnosed disorder with major personal and socioeconomic impact. Early diagnosis, patient and physician education, and effective withdrawal management are essential. Persistent gaps in pathophysiology, biomarkers, and tailored therapies demand further collaborative and multicenter research.

Instituciones: Universidad Nacional del Santa