The Hidden Risks of Medication Underuse in Migraine Progression

Migraine is a progressive neurological disorder in which inadequate treatment can lead to chronification. For decades, clinical attention has centered on medication overuse headache (MOH) as the primary iatrogenic risk factor for this progression. However, medication underuse (MU) has emerged as a critical yet less established framework for understanding gaps in migraine care. This review reframes MU, which includes ineffective therapies, delayed administration, and non-adherence due to intolerability, as an active contributor to disease progression. Untreated or undertreated migraine attacks promote the development of central sensitization, a state of neuronal hyperexcitability that increases attack frequency, severity, and treatment resistance. This paper posits that MU and MOH are not opposing concepts but interconnected manifestations of suboptimal disease management. Specifically, disease progression driven by MU can directly precipitate the escalating medication use that characterizes MOH, resulting in a more refractory clinical state. Therefore, preventing chronification requires a paradigm shift from merely avoiding overuse to achieving optimal use. This entails adherence to evidence-based guidelines for both acute and preventive therapy—implementing stratified acute care within the neurobiological window to prevent central sensitization and initiating timely preventive treatment in eligible patients to reduce the overall attack burden. The integration of novel targeted therapies provides new opportunities to overcome the limitations of traditional agents. Ultimately, reducing the risks associated with MU through proactive, evidence-based management and strong patient–clinician communication is essential to alter the natural history of migraine and prevent the long-term disability associated with its progression.