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.14Severe 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
A meta-analysis found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.
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.12There 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).
