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
August 8, 2026
Sugar is bad for your brain, even before you are born.
Sugar consumed in the first two years of life increases the risk of dementia.
Read article
August 6, 2026
Research
An Old Medicine that Could Make Brain Stimulation Work Better for Depression and Other Neurological Conditions
A 2022 clinical trial from the University of Calgary found that adding low‑dose D‑cycloserine (DCS), a partial NMDA‑receptor agonist, to intermittent theta‑burst stimulation (iTBS) significantly increased response and remission rates in depression without serious side effects. Early follow‑up data suggest that timing, dose, and drug levels matter, and raise the possibility that this DCS‑TMS approach could eventually be applied to other neurological conditions—such as migraine, postconcussion syndrome, brain fog, and long COVID
Read article
Insights from Dr. Alexander Mauskop on headaches and migraines
Subscribe to the Blog.
Subscribe
Subscribe