Medication Underuse Headache Demands Attention

Decreasing the number ofmigraine attacks and resolving each attack quickly when it occurs are more important than ever, according to an expert; the reason is that these strategies help prevent medication underuse headache (MUH). Anti-calcitonin gene–related peptide (CGRP) medications offer a promising preventive option for MUH, he added, particularly when given during low-frequency episodic attacks.

Red Flag

“The concept of medication underuse headache is so new that there are no accepted treatments or algorithms available yet,” said Alan M. Rapoport, MD. He is a clinical professor of neurology at the University of California, Los Angeles David Geffen School of Medicine; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

MUH is not a new headache subtype, Rapoport emphasized, but a warning sign on the road to migraine chronification and medication overuse headache (MOH). “Medication underuse headache is the cause of medication overuse headache,” he explained. “It is very important that we teach doctors and patients about medication underuse headache so we can prevent medication overuse headache. Once medication overuse headache begins, it is hard to treat.”

Authors, including Rapoport and Wanakorn Rattanawong, MD, of King Mongkut’s Institute of Technology Ladkrabang in Bangkok, Thailand, first proposed the MUH term in a review published in Cephalalgia in April 2024. The key to MUH prevention, Rapoport said in an interview, is using the right medication in the right dose at the right time, although each of these variables can pose challenges.

The Path to Chronification

Risk factors for migraine chronification remain incompletely understood, said Rapoport, but key triggers include MOH, migraine frequency increases (from once weekly to four or five times weekly), obesity, and possibly depression, anxiety, and sleep deprivation. With acute treatment, he said, the goal is to block the shift from peripheral to central nervous system sensitization and completely resolve migraine pain, disability, and potential recurrence.

Potential reasons for inadequate migraine treatment include physicians’ prescribing incorrect medication for the patient or failing to prescribe the most effective dose, which Rapoport said is usually the highest dose available. Additionally, patients may wait too long to take medication.

“The right time to start acute treatment is at the very start of a migraine attack,” or at least within 90 minutes of experiencing symptoms, said Rapoport. “As soon as the patient starts to feel nausea, light sensitivity, or the pain is beginning and feels to the patient that it will be a migraine, that’s the time to take the medication.”

If patients with multiple headache days weekly are unsure which will progress to migraines requiring a triptan or gepant, wrote Rapoport and colleagues, patients should take medication if the headache begins to intensify with unilateral throbbing and associated symptoms.

Preventive Medicines Underused

A study published in Neurology in 2007 revealed that although 38% of patients were eligible for migraine prevention medications, due to underprescribing, only 12.4% were on them. Moreover, a 2015 Cephalalgia publication showed that 12 months after receiving a prescription for a traditional oral migraine preventive, only 17%-20% of patients were still using them. As with acute treatments, primary reasons for discontinuing migraine prevention medications include lack of efficacy and tolerability issues, according to a study published in Headache in 2013.

“If a patient has four severe headache attacks a month,” Rapoport said, “they should be on preventive medication.” Preventive medication also may be appropriate for patients with one to two attacks monthly, which are so severe and/or treatment-resistant that patients desire prevention to be able to function, he added.

To reduce medication underutilization, Rapoport and colleagues wrote in their review, neurologists and patients must realize that older oral migraine preventive medications were not designed for migraine treatment but to treat other conditions such as hypertension and heart disease. Accordingly, reaching therapeutic blood levels and satisfactory efficacy may take 2-3 months, during which patients should be advised to ride out mild side effects.

Anti-CGRP Medications

Although older medications can work for both acute and preventive migraine care and reduce MUH risk, Rapoport said, these medications are typically less efficacious and cause many more troubling side effects than newer targeted anti-CGRP medications do.

“Preventively,” he said, “I prefer to use the newer anti-CGRP medicines; however, because they’re expensive and not always approved by insurance companies, sometimes we start with the older, less expensive medicines and progress to CGRP-targeting options if needed.”

Among physicians, Rapoport added, the biggest hurdle to broader acceptance of the MUH concept is lack of awareness. He said that when he and Rattanawong first presented the topic during the Spanish Society of Neurology’s annual meeting in November, they received no pushback but earnest questions about best clinical practices. On March 22, 2025, Rattanawong will participate in a debate on the validity of MUH during the 19th Annual World Congress on Controversies in Neurology in Prague, Czech Republic.

Rapoport is editor in chief of Neurology Reviews. The MUH paper received no funding.

John Jesitus is a Denver-based freelance medical writer and editor.