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1 "Central nervous system sensitization"
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Review Article
Finding the Sweet Spot between Medication Overuse and Underuse in Headache Medicine
Hong-Kyun Park
Received March 27, 2026  Accepted April 26, 2026  Published online June 15, 2026  
DOI: https://doi.org/10.62087/hpr.2026.0012    [Epub ahead of print]
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Medication-overuse headache (MOH) is a well-recognized secondary headache caused by the frequent use of acute symptomatic medications, particularly among patients with underlying primary headache disorders such as migraine. Medication-underuse headache (MUH) is a recently proposed conceptual framework describing the suboptimal use of indicated treatments, including underuse, delayed administration, poor adherence, or premature discontinuation, all of which may contribute to headache progression or chronification. Both conditions share pathophysiological substrates, including central sensitization, impaired descending pain modulation, and dysfunctional reward processing, which are rooted in dopaminergic mesocorticolimbic dysregulation and trigeminovascular sensitization. MUH may arise from fear of side effects, fear of withdrawal, poor adherence, or inadequate access to care and may lead to an escalating headache burden and increased reliance on acute treatments, potentially predisposing patients to MOH. Conversely, managing MOH without addressing underuse-related barriers may contribute to treatment resistance or relapse. Recent evidence suggests that calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies can achieve clinically meaningful improvement in MOH even without mandatory medication withdrawal, challenging the traditional assumption that detoxification is required for treatment response. MOH is also increasingly viewed as a multidimensional neurological and biobehavioral disorder, with preliminary neuroimaging data indicating that mindfulness-based interventions can modulate pain- and reward-related brain networks. This narrative review summarizes the clinical features and mechanisms of MOH and MUH and proposes a comprehensive management framework integrating patient education, structured lifestyle and mindfulness-based interventions, early initiation of preventive therapy, and CGRP-targeted treatments, with the aim of achieving therapeutic balance—not too much, not too little—and improving long-term outcomes.

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