Migraine headache: When to consider these newer agents
These agents are as effective as traditional acute and preventive treatments, cause fewer adverse effects, and can simplify regimens.
PRACTICE RECOMMENDATIONS
› Consider small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) for acute migraine treatment after treatment failure of at least 2 non-CGRP first-line therapies. A
› Consider anti-CGRP monoclonal antibodies or gepants for migraine prevention if traditional therapies have proven ineffective or are contraindicated or intolerable to the patient. A
› Add an anti-CGRP monoclonal antibody or gepant to existing preventive treatment if the patient continues to experience migraine. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Second-line therapies
Intranasal dihydroergotamine has a favorable adverse event profile and greater evidence for efficacy compared with ergotamine. Compared with triptans, intranasal dihydroergotamine has a high level of efficacy but causes more adverse effects.14 Severe nausea is common, and dihydroergotamine often is used in combination with an antiemetic drug. Dihydroergotamine should not be used within 24 hours of taking a triptan, and it is contraindicated for patients who have hypertension or ischemic heart disease or who are pregnant or breastfeeding. There is also the potential for adverse drug interactions.15
Antiemetics may be helpful for migraine associated with severe nausea or vomiting. The dopamine antagonists metoclopramide, prochlorperazine, and chlorpromazine have demonstrated benefit in randomized placebo-controlled trials.11 Ondansetron has not been studied extensively, but sometimes is used in clinical practice. Nonoral routes of administration may be useful in patients having trouble swallowing medications or in those experiencing significant nausea or vomiting early during migraine attacks.
Due to the high potential for abuse, opioids should not be used routinely for the treatment of migraine.12 There is no high-quality evidence supporting the efficacy of barbiturates (ie, butalbital-containing compounds) for acute migraine treatment.11 Moreover, use of these agents may increase the likelihood of progression from episodic to chronic migraine.16
Gepants for acute migraine treatment
Neuropeptide CGRP is released from trigeminal nerves and is a potent dilator of cerebral and dural vessels, playing a key role in regulating blood flow to the brain. Other roles of CGRP include the release of inflammatory agents from mast cells and the transmission of painful stimuli from intracranial vessels.17 The CGRP receptor or ligand can be targeted by small-molecule receptor antagonists for acute and preventive migraine treatment (and by monoclonal antibodies solely for prevention, discussed later). It has been theorized that gepants bind to CGRP receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.17 Unlike triptans and ergotamine derivatives, these novel treatments do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.
The 3 gepants approved for acute treatment—ubrogepant (Ubrelvy),18 rimegepant (Nurtec),19 and zavegepant (Zavzpret)20—were compared with placebo in clinical trials and were shown to increase the number of patients who were completely pain free at 2 hours, were free of the most bothersome associated symptom (photophobia, phonophobia, or nausea) at 2 hours, and remained pain free at 24 hours (TABLE 418-24).
Continue to: Ubrogrepant
