DHE (Dihydroergotamine) and Ergotamine

UseTreat moderate-to-severe migraines when they start (acute treatment); typically a second-line (or later) treatment.
EffectivenessDHE (dihydroergotamine) is more effective than ergotamine combinations, and these are more effective than ergotamine alone.1
Side effectsNausea (significant), leg cramps, tingling in the arms and legs
Taken how?Different formulations are available:
  • DHE nasal spray or injection
  • Ergotamine-combination tablet and rectal suppository
  • Ergotamine dissolving tablets
Drugs in this class
Brand Name(s)Generic Name
MigranalDHE nasal spray
DHE 45DHE injection
CafergotErgotamine/caffeine tablet
MigergotErgotamine/caffeine rectal suppository
ErgomarErgotamine dissolving tablets
Brand Name(s)Generic Name
MigranalDHE nasal spray
DHE 45DHE injection
CafergotErgotamine/caffeine tablet
MigergotErgotamine/caffeine rectal suppository
ErgomarErgotamine dissolving tablets

Ergotamine and the related drug DHE (dihydroergotamine) are some of the oldest migraine-specific medications.2 This group of drugs has been called many things: ergots, ergot derivatives, and ergot alkaloids. Ergots work seem to work by constricting the blood vessels in the brain.

The drugs in this group are used differently for treating migraine. They are not all equally effective and they have different side effects.

Migranal (DHE nasal spray): Effective second-line treatment

Migranal® (DHE nasal spray) is an effective acute treatment for moderate-to-severe migraine.3 DHE nasal spray is not usually a first choice of treatment because of side effects, cost, and the difficulty of using a nasal spray.4,5

In a high-quality trial, 27 percent of patients reported that they had no pain or mild pain 30 minutes after taking the nasal spray.6 Four hours after treatment, 70 percent of patients reported that their headache had resolved. Headache recurrence is uncommon with DHE. In one trial, headache pain recurred with 24 hours in 14 percent of patients.6 The risk of medication overuse headache with DHE is low.1

The nasal spray is expensive, although patients can save money using the generic form approved in 2020.7

DHE nasal spray is associated with more side effects than triptans, especially nausea. Anti-nausea medications may be given with DHE nasal spray. Other common side effects include stuffy nose, taste changes, or sore throat, dizziness, and fatigue.8 It can cause leg cramps or tingling in the arms and legs.4

Pregnant women cannot use DHE nasal spray.8 DHE nasal spray is also not for people with diseases that affect the heart, arteries, or circulation. It cannot be taken with medications that include CYP 3A4 inhibitors. CYP 3A4 inhibitors are found in some anti-HIV drugs and certain antibiotics. Combining DHE with a CPY 3A4 inhibitor could stop blood flow to the brain and/or limbs. All medications with DHE have a black box warning—the FDA’s strongest warning—against this combination.

DHE 45: Back-up relief

DHE 45 is an injectable form of DHE. DHE 45 is usually used to treat migraine after other treatments have failed.4 You can be trained to self-administer DHE 45 at home.9 It may also be given in the hospital along with anti-nausea medications.

Just like DHE nasal spray, DHE 45 should not be used by pregnant women or people with diseases that affect the heart, arteries, or circulation.9 DHE 45 cannot be taken with CYP 3A4 inhibitors.

Ergomar, Cafergot, Migergot (Ergotamine-based drugs): Less effective options

Ergotamine-based drugs are sometimes used as acute treatment for moderate-to-severe migraine. They are not the most effective medications for migraine. They can sometimes be useful to treat long-standing migraine attacks that keep recurring.2

Medications that combine ergotamine with caffeine (Cafergot® and Migergot®), seem to work better than ergotamine alone (Ergomar®).3 Caffeine improves absorption of ergotamine.10 Cafergot is a tablet taken by mouth. Migergot is taken as a rectal suppository, which can be helpful for people with nausea. Ergomar is a tablet that dissolves under the tongue.

How do ergots work?

Ergots work by binding to—or connecting with—serotonin receptors. Like triptans, ergots bind to subtypes of the receptor called 5-HT1B and 5-HT1D, as well as 5-HT1F.10 Binding to the 5-HT1B/D/F receptors in the brain reduces swelling in the blood vessels. This was once thought to be the way that ergots stopped migraine attacks. More recent research suggests they may also disrupt pain signals from the trigeminal nerves.10

Ergots also bind to 5-HT1A, 5-HT2A, and dopamine receptors. Binding to these receptors causes the unwanted side effects, such as nausea, vomiting, and dysphoria.10 Contraction of blood vessels in the hands and feet causes cramps and tingling.11

This is not an exhaustive list of all potential side effects of ergots. For more information, consult your doctor or healthcare provider. If you notice any new or worsening side effects, contact your doctor or healthcare provider immediately.

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Written by: Sarah O'Brien | Reviewed June 2021