New ACP Migraine Guidelines Show No Advantage for Pricy, Newer Medications

Amir Qaseem, MD, PhD, MHA

Credit: American College of Physicians

The American College of Physicians (ACP) has developed new recommendations to prevent episodic migraines, indicating no clinical advantage for newer, expensive medications.¹ Rather, the ACP recommends monotherapy to prevent episodic migraine headaches in nonpregnant adults with a beta-adrenergic blocker (metoprolol or propranolol), antiseizure medication valproate, the serotonin and norepinephrine reuptake inhibitor venlafaxine, or the tricyclic antidepressant amitriptyline.

If patients do not respond to or tolerate monotherapy, ACP recommends a monotherapy with a calcitonin gene-related peptide (CGRP) antagonist (atogepant or rimegepant) or a CGRP monoclonal antibody (eptinezumab, erenumab, fremanezumab, or galcanezumab). If patients still do not respond to or tolerate treatment, the guidelines recommend monotherapy with the antiseizure medication topiramate. The guidelines stress the importance of a patient’s adherence to a pharmacologic treatment since improvement may occur gradually, with an effect present after the first few weeks of treatment.

Newer, more expensive medications, such as ubrogepant ($1045) and dihydroergotamine mesylate nasal spray ($269.43), the lowest available costs reported by GoodRx, were not mentioned in the guidelines.^2,3

Migraine, characterized by recurrent episodes of moderate-to-severe intensity headache lasting 4 – 72 hours, is the second leading cause of global disability in adults—and the top cause in females aged 15 – 49 years.¹ Approximately 16% of people in the US have migraine, and migraine has accounted for about 4 million emergency department visits and > 4.5 million office visits in a year. The condition creates a substantial economic burden of > $78 billion annually in medical expenses.

Migraine can occur with or without sensory disturbances. People who experience a migraine can have nausea, vomiting, or aversion to light or sound. Despite its high disability and burden, migraine is often underdiagnosed and undertreated, resulting in only a small percentage of people receiving preventive pharmacologic treatments.

Many pharmacologic treatments for migraine were originally developed for other conditions and are used off-label for this indication, such as angiotensin-converting enzyme inhibitors and angiotensin II–-receptor blockers. The FDA has approved some drugs for migraine, including propranolol, topiramate, and valproate, with newer options of calcitonin gene-related peptide antagonists and monoclonal antibodies.

The updated migraine guidelines were informed by a comparative effectiveness systematic review that used the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach to assess the effects of pharmacologic treatment to prevent episodic migraine. The review evaluated the following outcomes: migraine frequency and duration, number of days medication was taken for acute treatment of migraine, frequency of migraine-related emergency room visits, migraine-related disability, quality of life, physical function, and discontinuations due to adverse events. Treatments assessed included:

• Angiotensin-converting enzyme inhibitors (lisinopril)
• Angiotensin II–receptor blockers (candesartan and telmisartan)
• Antiseizure medications (valproate and topiramate)
• β-blockers (metoprolol and propranolol)
• Calcitonin gene-related peptide (CGRP)
• Antagonist-gepants (atogepant or rimegepant)
• CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, or galcanezumab)
• Selective serotonin reuptake inhibitors
• Serotonin and norepinephrine reuptake inhibitors (fluoxetine and venlafaxine)
• Tricyclic antidepressant (amitriptyline)

The analysis discovered a lack of difference in clinical benefit between all treatments. Thus, investigators decided to look at the advantages of the treatments from an economic standpoint instead, collecting financial data and patients’ values and preferences. The analysis saw the median annual costs of recommended initial oral treatments varied drastically.

The annual cost of injectable CGRP-mAbs (eptinezumab, erenumab, fremanezumab, and galcanezumab) or oral CGRP antagonists-gepants (atogepant and rimegepant) ranged from $7071 to $22 790, and the analysis showed with low certainty that these drugs may have intermediate value compared with no preventative people in people with ≥ 1 previous treatment failure. Moreover, the recommended initial treatments— metoprolol [$123], propranolol [$393], valproate [$274], venlafaxine [$378], and amitriptyline [$67]—had substantially lower annual mean costs.

Due to inconclusive findings, the CGC had no recommendations for the ACE inhibitor lisinopril, the ARBs candesartan and telmisartan, and the SSRI fluoxetine.

“As a result, the CGC suggests that clinicians and patients use a β-blocker (metoprolol or propranolol), the antiseizure medication valproate, the SNRI venlafaxine, or the TCA amitriptyline to prevent episodic migraine headache in nonpregnant adults before using a CGRP-mAb or a CGRP antagonist-gepant,” wrote the ACP, led by Amir Qaseem, MD, PhD, MHA.

References

1. ^{Qaseem A, Cooney TG, Etxeandia-Ikobaltzeta I, Wilt TJ, Harrod CS, Tice JA, Crandall CJ; Clinical Guidelines Committee of the American College of Physicians; Hicks LA, Cross JT Jr, Fitterman N, Lewis J, Linsky AM, Maroto M, Miller MC, Obley AJ, Owens DK, Shekelle PG, Shamliyan T, Yost J. Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline From the American College of Physicians. Ann Intern Med. 2025 Feb 4. doi: 10.7326/ANNALS-24-01052. Epub ahead of print. PMID: 39899861.}
2. ^{Migraine Medications. GoodRx. https://www.goodrx.com/conditions/migraine/drugs. Accessed February 5, 2025.}
3. ^{Dihydroergotamine Mesylate; form: nasal spray. GoodRx. https://www.goodrx.com/dihydroergotamine-mesylate?label_override=dihydroergotamine-mesylate&dosage=8-vials-of-4mg-ml&form=nasal-spray&quantity=1. Accessed February 5, 2025.}