Ergot Alkaloids for Migraine

Medically Reviewed by Murtaza Cassoobhoy, MD on February 10, 2023
5 min read

Ergot alkaloids are a group of headache medicines that include dihydroergotamine (Migranal, Trudhesa, others) and ergotamine (Cafergot, Ergomar, Ergostat, others). These drugs are used only to treat severe, throbbing headaches like migraine and cluster headaches.

Ergot alkaloids are among the oldest headache treatments. They were developed in the 1920s, and doctors have been prescribing them to manage headaches since the 1940s.

They aren't the same as triptans, a newer class of migraine medicine that came out in the 1990s. Triptans and ergot alkaloids work in similar ways, by narrowing blood vessels in the brain to relieve headaches. Triptans start to work faster than ergot alkaloids and cause fewer side effects. But their pain relief effects don't last as long.

Although we don't know the exact cause of migraine, one theory is that the pain starts with chemicals called neurotransmitters that help nerve cells communicate. Waves of brain cell activity cause changes in the levels of these chemicals, which leads to throbbing pain. These changes also cause blood vessels to dilate (widen), which makes the pain worse.

Ergot alkaloids work by narrowing blood vessels in the brain. These drugs affect levels of the chemical messenger serotonin, which also narrows blood vessels. They also stop a nerve in the brain called the trigeminal nerve from releasing proteins that cause inflammation.

Some ergot alkaloid products add caffeine to help your body absorb the medicine better. This can help the drug start to work more quickly.

Other ergot alkaloids include an antihistamine like dimenhydrinate or diphenhydramine to relieve the nausea and vomiting that often come with a migraine. These ingredients also help you sleep.

Ergot alkaloids might not completely get rid of migraine, but they should work quickly to make these headaches less intense and more manageable.

Because ergot alkaloids can cause severe side effects, doctors often don't prescribe them as the first treatment for migraine. Your doctor may not recommend them until after you've tried pain relievers like aspirin, ibuprofen (Advil, Motrin), or acetaminophen (Tylenol).

Ergot alkaloids are usually reserved for people who get frequent migraine or whose headaches last for longer than 2 days.

Ergotamine comes as a nasal spray, a suppository, a pill, and a type of pill that dissolves under your tongue (sublingual). Don't chew or swallow the sublingual pill because it may not work as well. Start with one tablet. You can take another one in 30 minutes if your headache hasn’t improved, but don’t take more than three pills in 1 day.

Ergotamine plus caffeine comes as a tablet or suppository. You take two tablets at the first sign of a migraine. If the headache doesn’t improve, take another one or two tablets every 30 minutes until it goes away. Never take more than six tablets in any 24-hour period.

You may want to take ergotamine as a suppository if you have severe nausea and can’t keep a pill down.

To use the suppository, you first unwrap it and then dip the tip into water. To insert it, lie on your side and use a finger to gently push the suppository into your rectum. Wash your hands after you’ve inserted it and lie back down quietly to allow the medicine to work. If your headache doesn't improve within 1 hour, you can take another suppository.

Dihydroergotamine comes as a shot or a nasal spray. You can get the shot at your doctor's office or a hospital, or your doctor can teach you how to inject it yourself. One advantage to the injectable and spray methods is they work quickly. But they can also cause more side effects than pills.

Ergot alkaloids work best if you take them as soon as your migraine starts. If you get aura or other warning signs before a headache, you can take the medicine even before the headache starts. After you take the medicine, lie down in a dark room for 2 hours to give it a chance to work.

Don't take these medicines more often than your doctor recommends. Overusing ergot alkaloids can make them less effective.

Because ergot alkaloids narrow blood vessels, they can affect many parts of your body. The most common side effects from these medications include:

  • Nausea and vomiting
  • Dizziness
  • Numbness and tingling
  • High blood pressure
  • Slow or fast heartbeat
  • Muscle pain in the arms or legs
  • Itching

Some people become dependent on ergot alkaloids and develop rebound headaches. The medicine stops working and the headaches get worse. You may feel like you need to take more of the drug to get the same relief, but taking a higher dose than your doctor prescribed could increase the side effects and even cause death.

If you have headaches and find yourself taking an ergot alkaloid every day or every other day, talk to your doctor. To stop the rebound headaches, you’ll need to stop taking this medication. It can take some time before the rebound headaches stop.

Ergot alkaloids can interact with certain medications. Let your doctor and pharmacist know about all the prescription and over-the-counter medicines, vitamins, and supplements you take before you start taking a migraine medicine.

These medications can also interact with grapefruit. Don’t drink grapefruit juice or eat grapefruit while taking an ergot alkaloid without talking to your doctor first.

Pregnant women should not take ergot alkaloids. These medicines can harm a growing baby and increase the risk for miscarriage.

If you're nursing, check with your doctor before taking ergot alkaloids. The medication can reduce the amount of milk you make. It can also pass into the breast milk and cause problems like these in your baby:

  • Vomiting
  • Diarrhea
  • Seizures
  • Blood pressure changes

Taking an ergot alkaloid can also be riskier for people who have had these conditions:

  • Hemiplegic migraine (migraine with weakness on one side of the body)
  • Heart disease
  • Heart attack
  • Stroke or transient ischemic attack (TIA)
  • High blood pressure or high cholesterol
  • Diabetes
  • Raynaud's disease
  • Circulation problems
  • Blood vessel or heart surgery
  • Kidney, liver, or lung disease

You should not take ergot alkaloids with CYP3A4 inhibitors like some antibiotics, antifungal medicines, and HIV drugs. These medications slow the rate at which your body breaks down and removes ergot alkaloids. A buildup of medication in your body could lead to more serious side effects.

Your doctor should go over your medical history before they prescribe an ergot alkaloid for you.