100 Migraine Drugs, A to Z: dihydroergotamine

October 29, 2018

Dihydroergotamine (DHE-45) when given intravenously (IV) is considered to be the most effective migraine medication. It was introduced in 1943 and has been the go-to drug for migraines that do not respond to other medications. We usually consider using dihydroergotamine (DHE) after the failure of oral triptans, nonsteroidal antiinflammatory and steroid drugs, as well as injections of ketorolac (Toradol), sumatriptan (Imitrex), and metoclopramide (Reglan), and in some patients, nerve blocks.

Raskin protocol, named after Neil Raskin who still practices headache medicine in San Francisco, calls for IV DHE with metoclopramide to be given every 8 hours to break a persistent migraine attack that does not respond to other measures.

The Raskin protocol is typically administered in a hospital. However, if the patient is able to, we sometimes have her come in for an infusion in the morning and a second time in the late afternoon. DHE often worsens nausea and we usually pretreat patients with ondansetron (Zofran) or metoclopramide. A minority of patients do not experience nausea with their migraines and they usually do not develop it with dihydroergotamine.

A few of our patients self-administer this drug subcutaneously at home. Subcutaneous injection is not as effective as when the drug is given intravenously, but for some patients it works very well. Some take an oral nausea medication or even self-inject a nausea drug prior to giving themselves an injection of DHE. DHE is available only in glass vials and it is prescribed with a syringe.

Dihydroergotamine nasal spray (Migranal) has been available for over a decade and its approval was based on a double-blind trial in 348 patients. The results of this trial are impressive, but in clinical practice I do not find it to be highly effective.

Headache specialists were very excited with the results of studies showing that inhaling DHE into the lungs provides excellent and consistent relief with few side effects. The FDA had accepted the safety and the efficacy data, effectively approving the drug (to be called Levadex and then, Semprana). However the FDA had found manufacturing inconsistencies. The small company that developed inhaled DHE, MAP Pharmaceuticals was acquired by Allergan (for close to a billion dollars). Unfortunately, after five years of failed efforts it seems that Allergan has given up on trying to fix the production problem.

Written by
Alexander Mauskop, MD
Continue reading
December 15, 2025
Alternative Therapies
Could drugs like Ozempic, Saxenda, and Zepbound help migraines?
Could drugs like Ozempic, Saxenda, and Zepbound help migraines? Extra weight often increases migraine headache frequency and makes standard treatments less effective. But a study just published in the journal Headache shows that a medication commonly used for weight loss and diabetes, liraglutide (Saxenda), might offer relief for tough-to-treat migraines in people with obesity.
Read article
November 15, 2025
Cluster headaches
Cluster headaches and solar activity
It was an unusual week at the New York Headache Center. After months of relative calm, my schedule suddenly filled with cluster headache patients—one even consulting me virtually from Saudi Arabia. The influx came right after a G5-level geomagnetic storm, one of the strongest solar events in recent memory.
Read article
November 10, 2025
Alternative Therapies
A Week of Meditation Changes Brains and Bodies
A week-long meditation retreat produces dramatic changes in brain and metabolic functions
Read article