ACP urges cost-effective migraine prevention over expensive new medications

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Approximately 16% of Americans are affected by migraine, and more females than males (21% to 11%). The second leading cause of global disability, migraine accounts for approximately four million emergency department (ED) visits, and more than 4.3 million office visits each year, costing the U.S. $78 billion annually in medical expenses and lost productivity.

The American College of Physicians (ACP) has released a new clinical guideline for the prevention of episodic migraine headaches in non-pregnant adults in outpatient settings. The guideline, published in Annals of Internal Medicine, includes three recommendations centered around monotherapy. Developed by a multidisciplinary panel, the guideline evaluates a wide range of medications for adults experiencing 1–14 headache days per month.

Three recommendations

Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, the ACP guideline offers conditional recommendations — each based on low-certainty evidence — designed to help clinicians tailor treatment plans.

In recommendation one, the guideline advises initiating monotherapy to prevent episodic migraine headache in non-pregnant adults in outpatient settings through one of the following pharmacologic options:

• Beta-adrenergic blockers: Metoprolol or propranolol
• Anti-seizure medication: Valproate
• Serotonin and norepinephrine reuptake inhibitor (SNRI): Venlafaxine
• Tricyclic antidepressant: Amitriptyline

In recommendation two, for patients who do not tolerate or adequately respond to these initial options, the guideline suggests that clinicians use monotherapy with a calcitonin gene-related peptide (CGRP) antagonist — atogepant or rimegepant — or a CGRP monoclonal antibody (CGRP-mAbs) — eptinezumab, erenumab, fremanezumab, or galcanezumab.

If these alternatives also prove ineffective, the recommendation three suggests that clinicians use monotherapy with the anti-seizure medication topiramate.

Reasoning

The guideline committee emphasized economic evidence and patient preferences in shaping its recommendations, as no single migraine prevention treatment showed a clear net benefit over others. Although low-certainty evidence suggested that beta blockers and CGRP-mAbs may offer small advantages over topiramate — mainly citing fewer discontinuations from adverse effects — most treatment comparisons showed little to no meaningful difference.

CGRP-mAbs may also reduce migraine frequency and the need for acute medication compared with topiramate, while venlafaxine may slightly reduce migraine duration versus amitriptyline. However, the certainty of these findings remains low.

Cost was a key factor, with CGRP-targeted therapies being significantly more expensive than beta blockers, amitriptyline, topiramate and valproate. Additionally, patients tend to prefer oral medications over injectables, further supporting the guideline’s emphasis on cost-effective first-line options.

Adverse events varied by drug class, but most were mild, with topiramate associated with higher rates of side effects. The committee prioritized treatments with similar efficacy but better tolerability and affordability to improve access and reduce healthcare disparities.

The guideline omits certain drugs, including as ACE inhibitors, ARBs, or SSRIs, due to a lack of comparative data or insufficient evidence. Additionally, there were no comparative findings on emergency department visits or physical functioning improvements. Clinicians are encouraged to discuss side effect profiles and U.S. Food and Drug Administration (FDA) warnings when guiding patients through treatment options.

With an emphasis on cost-effective options with comparable efficacy, ACP’s newest guideline aims to improve access to migraine prevention. Clinicians should tailor treatment discussions to align with patient preferences and financial concerns before making evidence-based recommendations.