Migraine
Lauren Howell, PharmD
In February 2025, the American College of Physicians (ACP) released new guidelines to prevent episodic migraine headache using pharmacologic treatments in outpatient settings. The guidelines were developed for clinicians who provide care to adults with episodic migraine headache, which is defined as 1 to 14 headache days per month.
The recommendations in the guidelines are based on systematic reviews of pharmacologic treatments to prevent episodic migraine, as well as patients’ values and preferences. They are the first recommendations to include economic evidence since new drugs that have come to market in recent years are more expensive.
The pharmacologic agents that were considered include ACE inhibitors (lisinopril), ARBs (candesartan and telmisartan), antiseizure medications (valproate and topiramate), b-blockers (metoprolol and propranolol), calcitonin gene-related peptide (CGRP) antagonists (atogepant and rimegepant), CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab), SSRIs and SNRIs (fluoxetine and venlafaxine), and tricyclic antidepressants (amitriptyline).
The recommendations
In the new recommendations, ACP suggests that in nonpregnant adults in outpatient settings, monotherapy can be initiated to prevent episodic migraine. The suggested first-line monotherapy agents include metoprolol, propranolol, valproate, venlafaxine, or amitriptyline.
ACP also said clinicians should use monotherapy with a CGRP antagonist (atogepant or rimegepant) or a CGRP monoclonal antibody (eptinezumab, erenumab, fremanezumab, or galcanezumab) to prevent episodic migraine headache in nonpregnant adults in outpatient settings who do not tolerate or inadequately respond to a trial of metoprolol, propranolol, valproate, venlafaxine, or amitriptyline.
The last recommendation of the three total recommendations from ACP calls for clinicians to use monotherapy with the antiseizure medication topiramate to prevent episodic migraine headache in nonpregnant adults in outpatient settings who do not tolerate or inadequately respond to a trial of metoprolol, propranolol, valproate, venlafaxine, or amitriptyline and a further trial with a CGRP antagonist or a CGRP monoclonal antibody.
All three recommendations are considered conditional recommendations with low certainty of evidence, meaning that the benefits probably outweigh the risks and burden. They also apply to many patients but may differ depending on circumstances, and the confidence in the estimated effect is limited.
According to ACP, clinicians should use an informed decision-making approach and discuss benefits, harms, costs, patient values and preferences, financial burden, mode of administration, pregnancy and reproductive status, clinical comorbidities, and availability when selecting an agent to prevent episodic migraine.
Clinical considerations
Currently, evidence-based definitions or thresholds for when to initiate pharmacologic treatments to prevent episodic migraine are lacking.
ACP suggests that pharmacologic treatment for preventing migraine be considered in people who experience severe debilitating headache despite adequate acute treatment and also for those who are unable to tolerate or have contraindications to acute treatment or are using their acute treatment more than recommended.
When a pharmacologic agent is initiated, ACP guideline authors said patients should be counseled on the importance of adherence and that the desired effect may not become apparent until after the first few weeks of treatment.
If the recommended treatments are not tolerated or do not work well for a patient, clinicians may consider lisinopril, candesartan, telmisartan, or fluoxetine as an alternative option, according to ACP. These medications were not included in the main recommendations due to limited evidence from studies with small sample sizes, the possibility of bias in the studies, supporting efficacy, and the lack of comparative effectiveness data.
Any pharmacologic agent that is initiated should be started at a low dose and gradually increased until the desired effect is achieved. If an adequate response is not achieved after 2 to 3 months, or an adverse effect occurs, it is appropriate to switch the pharmacologic agent that is used.
Before a patient starts any medication to prevent episodic migraine, they should be counseled on modifiable triggers and factors that contribute to an acute migraine. Lifestyle interventions, such as hydration, regular and adequate sleep, and physical activity, should all be considered before a medication is prescribed. Additionally, certain behavioral interventions, including cognitive behavioral therapy, relaxation training, or mindfulness-based treatment may decrease the frequency of migraine headaches without requiring any pharmacological intervention. ■