Getting Ahead of Migraines With Current and Emerging Approaches

Besides acetaminophen, NSAIDs, triptans, ergot alkaloids, and adjunct antiemetics, gepants and ditans are recently approved for migraine patients.

In a review published in The Lancet, researchers discussed the current pharmacologic and nonpharmacologic therapies for managing migraines as well as the up-and-coming strategies.

Pharmacologic therapy is the mainstay in the treatment toolbox for migraines. The International Headache Society defined successful treatment as resolution of pain and/or resolution of secondary symptoms (such as nausea, vomiting, phonophobia, and photophobia) within 2 hours of using a medication.

Besides the traditional pharmacologic options of acetaminophen (paracetamol), nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, ergot alkaloids, and adjunct antiemetics, gepants and ditans have recently been approved for use.

Gepants are small-molecule calcitonin gene-related peptide receptor antagonists. Currently 2 gepants have been approved. Ubrogepant was found to relieve migraine pain within 2 hours at a dose of 50 mg among 22% of patients with moderate to severe headache. Rimegepant had similar results (21%) with a dose of 75 mg.

The approved ditan is called lasmiditan. At trial, 32% of patients with moderate to severe headache had pain relief within 2 hours of taking 200 mg. Because this drug impairs the ability to drive, patients should be advised not to operate a vehicle or machinery for 8 hours, meaning it may not be a suitable option for many patients.

Trials are now ongoing for 3 additional medications. Two gepants, atogepant and rimegepant, were found to be superior to placebo during phase 2b/3 trials, but they require additional evaluation of efficacy, tolerability, and safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a signaling molecule; an anti-PACAP monoclonal antibody is currently in phase 1 of testing, but a similar monoclonal antibody did not pass the phase 2 stage.

Pharmacologic preventive strategies have been recommended by the European Headache Federation for patients who experience 2 or more attacks per month, have impaired quality of life, and for whom acute medications have failed or are overused. Current options include antidepressants, antihypertensives, anticonvulsants, flunarizine, onabotulinumtoxinA, and anti-CGRP (calcitonin gene-related peptide) monoclonal antibodies. The review authors cautioned that in most cases, the clinical trials for many of these options were underpowered and poorly designed.

The nonpharmacologic options of neuromodulatory devices, biobehavioral therapies, dietary modulation, physical therapy, sleep modulation, and acupuncture may be used alone or in combination with pharmacologic options.

In general, migraine is a heterogeneous disorder and symptoms vary from patient to patient. Clinicians should prioritize patient education about the disease itself and about all treatment options to fully understand the patient’s preference and to ensure treatment compliance.

The review authors concluded that although novel mechanisms for mitigating symptoms of migraine have been developed, the biological underpinnings of the disease remain poorly understood. Improved understanding of migraine biology will likely improve patient-focused precision medicine strategies.

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


Ashina M, Buse DC, Ashina H, et al. Migraine: integrated approaches to clinical management and emerging treatments. Lancet. 2021;397(10283):1505-1518. doi:10.1016/S0140-6736(20)32342-4

This article originally appeared on Neurology Advisor