ACP Issues Clinical Guideline for Episodic Migraine With Pharmacologic Treatments

The American College of Physicians (ACP) released a new clinical practice guideline on the pharmacologic prevention of episodic migraine among adults who are not pregnant or lactating. The clinical guideline was published in the Annals of Internal Medicine.

In the United States, approximately 21% of women and 11% of men are affected by migraine, which presents as a moderate to severe headache with or without aura lasting 4 to 72 hours, according to the guideline authors. Episodic migraine is defined as experiencing 1 to 14 headache days per month. Annual medical expenditures and lost productivity associated with migraine is estimated to exceed $78 billion, making the prevention of migraine an important unmet clinical and societal need.

However, migraine is undertreated. In one study, referenced in the ACP guideline, researchers estimated that although 40% of individuals in the US with migraine were eligible for pharmacologic treatment, only 17% were using pharmacology for migraine.

Pharmacologic Treatments for Episodic Migraine

The new ACP guideline aims to inform physicians and other clinicians who treat individuals in the outpatient setting about the current pharmacologic treatment landscape for episodic migraine.

The drug classes considered in these guidelines were evaluated for safety and efficacy in placebo-controlled studies and included:

• angiotensin-converting enzyme inhibitors (ACEis);
• antidepressants;
• anticonvulsants;
• angiotensin II–receptor blockers (ARBs);
• beta-adrenergic blockers;
• calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs); and
• CGRP antagonists-gepants.

3 Monotherapy-Centric Recommendations for Episodic Migraine

On the basis of a systematic review of all available evidence, the ACP has made a total of 3 recommendations for the treatment of episodic migraine, all with low certainty of evidence. The guideline authors note that current evidence does not clearly favor any pharmacologic treatment over another. Instead, these recommendations largely rely on economic and patient preference data.

First Recommendation

The ACP suggests for adults who are not pregnant, clinicians should initiate monotherapy to prevent episodic migraine with the following:

• beta-adrenergic blockers metoprolol or propranolol;
• the antiseizure medication valproate;
• the serotonin and norepinephrine reuptake inhibitor venlafaxine; or
• the tricyclic antidepressant amitriptyline.

Second Recommendation

For their second recommendation, the ACP suggests for adults who are not pregnant and who do not tolerate or respond to the previously recommended therapies for episodic migraine, clinicians should initiate monotherapy with:

• the CGRP antagonists-gepants atogepant or rimegepant; or
• the CGRP mAbs eptinezumab, erenumab, fremanezumab, or galcanezumab.

Third Recommendation

The ACP suggests for adults who are not pregnant and who do not tolerate or respond to the previously recommended therapies, clinicians should initiate monotherapy with the antiseizure medication topiramate.

The Annual Cost of Medications for Episodic Migraine

Compared with the annual cost of medications listed in the second recommendation (atogepant, eptinezumab, erenumab, fremanezumab, galcanezumab, and rimegepant; median range, $7071-$22,790), the cost of these migraine prevention medications is lowest for:

• amitriptyline (median, $67),
• metoprolol (median, $123),
• valproate (median, $274),
• venlafaxine (median, $378), and
• propranolol (median, $393).

Weighing Patient Preferences for Episodic Migraine Treatment

According to the ACP guideline, in studies that have evaluated patient value, researchers found patients have a preference for oral medications vs injectable medications and, in general, patients prioritize migraine-related outcomes over adverse effects. As such, the medications in the first rather than the second recommendation reflect patient’s preference for formulation and efficacy.

Topiramate for Episodic Migraine: A Last Resort

The ACP’s guidance for using topiramate as a last resort is due to its safety and efficacy profiles. Studies with low-certainty of evidence report that compared with beta-blockers, topiramate is associated with more discontinuations due to adverse events. Moreover, compared with CGRP mAbs, its use is associated with both a greater frequency of migraine and use of acute medication.

Pharmacotherapy Considerations

In all cases, the ACP recommends that clinicians should explore modifiable environmental triggers of headache prior to initiating pharmacotherapy, such as staying hydrated, engaging in physical activity, and obtaining adequate sleep. However, pharmacotherapy should be considered for individuals with severe, debilitating headache, despite environmental or lifestyle modifications and acute treatment.

When considering pharmacotherapy, clinicians should use informed decision-making and discuss the potential benefits, harms, costs, contraindications, and effects to reproduction with patients before starting any episodic migraine pharmacologic preventative treatment.

Addressing Research Gaps in Episodic Migraine Prevention

The ACP highlights multiple gaps in research on the prevention of episodic migraine. Specifically, there is a dearth of head-to-head trials between different drug classes, no or inadequately designed placebo-controlled trials have been conducted for multiple eligible drugs, and some subgroups of patients are underrepresented in the literature.

Due to the lack of placebo-controlled trials or because of insufficient treatment durations in trials, the ACP is unable to make recommendations about:

• the ACEis captopril and enalapril;
• the antidepressants doxepin, duloxetine, and nortriptyline;
• the anticonvulsants gabapentin, lamotrigine, and valproate-topiramate; or
• any calcium-channel blockers.

“In this guideline, ACP makes recommendations for clinicians to initiate monotherapy for episodic migraine prevention in nonpregnant adults in the outpatient setting as well as alternative approaches if initial treatments are not tolerated or result in an inadequate response. All 3 ACP recommendations have conditional strength and low-certainty evidence,” the guideline authors concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.