Migraine: Much Progress Made, Significantly More Needed

Migraine is the second leading cause of global disability, impacting an estimated 39 million Americans.¹ Despite the well documented socioeconomic impact of the pathology, gaps in preventive therapeutic strategies persist.²

Image Credit: Adobe Stock - Artem Furman

Although an established standard of care for migraine prophylaxis exists, the current protocol is not without significant shortcomings. A group of researchers from Italy have summarized the unmet needs in a review published in Neurology & Therapy.²

The goals of preventive treatment are to decrease attack frequency and intensity and to reduce the risk of progression to chronic migraine. Indications for initiation of migraine prophylaxis include:³

• 4 or more headaches per month and/or 8 or more headache days per month
• debilitating attacks despite acute therapy
• difficulty tolerating/contraindication to acute therapy
• overuse of acute headache medications
• presence of migraine subtype

Recent data suggest that nearly 40% of patients with episodic migraine could benefit from starting prophylaxis, but only around 10% of those patients initiate therapy.² This gap highlights a dilemma for both patients and general practitioners (GPs).

Without proper diagnosis, patients often prolong the initiation of adequate treatment, which can harm the physician-patient relationship. GPs and pharmacists have an opportunity to provide resources to further educate patients on proper medication use and reiterate treatment goals. To optimize care, providers must identify patients eligible for newer therapies and refer them to established headache centers.²

Traditional medication classes utilized in migraine prophylaxis include beta blockers, calcium channel blockers, antidepressants, and anticonvulsants. Adverse effects (AEs) are common with these therapies, complicating treatment plans.

Beta blockers (e.g., propranolol) can cause bradycardia, weight gain, and erectile dysfunction. Amitriptyline often causes drowsiness and constipation. Topiramate—the primary anticonvulsant used in migraine prophylaxis—can cause weight loss, depression, and fetotoxicity.

Fetotoxicity is particularly concerning because migraine currently represents the most common cause of work disability in young women of childbearing age. AEs can lead to inappropriate medication use and overall dissatisfaction with care. This increases the risk of evolution to chronic migraine or the onset of medication overuse headache.²

The introduction of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) signaling pathway provide a novel approach to migraine prophylaxis.⁴ Current FDA-approved mAbs acting on CGRP or its receptor include erenumab, eptinezumab, galcanezumab, and fremanezumab. AEs are minimal compared to traditional treatments and consist primarily of injection site reactions and constipation.⁴

This promising therapeutic class has its own limitations. Despite the well-documented efficacy of CGRP inhibitors, they only benefit a fraction of patients.² These agents’ high cost hinders the potential of first-line usage. In addition, little is known about potential AEs in pregnancy or use in patients with cardiovascular diseases outside the age group of 18 to 65 years.²

The revolution of migraine prophylaxis presents an opportunity to modify the outdated current protocol. New therapies may pave the way for abandoning traditional medications.

Continuing education for patients and providers is crucial to successful treatment. A migraine prophylaxis diagnosis can prevent breakthrough therapy misuse and eliminate the need for detoxification from those therapies. By addressing knowledge and access gaps in preventive treatment, the standard of care can match the expectations of migraine sufferers.

About the Author

Jack Vinciguerra, PharmD, is a community pharmacist based in New York.

References

1. Burch RC, Buse DC, Lipton RB. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019;37(4):631-649. doi: 10.1016/j.ncl.2019.06.001

2. Bentivegna E, Onan D, Martelletti P. Unmet Needs in Preventive Treatment of Migraine. Neurol Ther. 2023;12(2):337-342. doi:10.1007/s40120-023-00438-z

3. Ha H, Gonzalez A. Migraine Headache Prophylaxis. Am Fam Physician. 2019;99(1):17-24.

4. Rashid, Abin, and Ali Manghi. “Calcitonin Gene-Related Peptide Receptor.” National Center for Biotechnology Information. July 22, 2022. Accessed May 17, 2023. www.ncbi.nlm.nih.gov/books/NBK560648/