News Release

Doubling down on headache pain

Study says combo of common drugs may provide headache relief after injury

Peer-Reviewed Publication

American Academy of Neurology

MINNEAPOLIS - It's not uncommon for people who experience a concussion to have moderate to severe headaches in the weeks after the injury. A new study has found a combination of two drugs, both common anti-nausea medications, given intravenously in the emergency room may relieve those headaches better than a placebo. The study is published in the March 24, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Metoclopramide is an anti-nausea medicine sometimes used to treat migraine. Diphenhydramine is a common antihistamine that when used in its injected form can treat motion sickness. Higher doses of metoclopramide given intravenously can cause restlessness, so this study combined diphenhydramine with metoclopramide to prevent those symptoms.

"The headaches you get after a trauma like a fall, an assault or car accident can linger for months or even years and lead to a reduced quality of life, so the results of our study are promising," said study author Benjamin W. Friedman, M.D., of Albert Einstein College of Medicine, Bronx, N.Y.

The study involved 160 people who experienced a head trauma and then visited an emergency room because of a headache within 10 days. They were randomly assigned to two groups: 81 people were given 20 milligrams (mg) of metoclopramide and 25 mg of diphenhydramine intravenously. The remaining 79 people were given an injection of saline solution as a placebo.

Researchers asked people to rate the intensity of their pain on a scale of zero to 10 one hour after the medication was administered. On this scale, zero means no pain and 10 means the worst pain imaginable.

The study found that the drug combination reduced the average person's pain level by more than five points one hour later. People in the group given the combination of metoclopramide and diphenhydramine said they improved, on average, by 5.2 points on the pain scale. People in the group given a placebo, on average, said their pain improved by 3.8 points on the pain scale.

In the group given the drug combination, 43% experienced side effects like drowsiness, restlessness or diarrhea. In the group given the placebo, 28% of the people reported those kinds of side effects.

"More research is needed to determine the most effective dose of metoclopramide, and how long to administer it, to see if people can get longer-term relief after they leave the emergency room," Friedman said. "Also, future work may be able to determine whether early treatment with this medication can target other disruptive symptoms you may get after a head injury, like depression, sleep disorders and anxiety."

A limitation of the study is that the study participants came from high poverty areas of the country, and may have had less access to care. Because successful headache treatment may be associated with access to care, these results may not apply to the general population.


The study received support from the Harold and Muriel Block Institute for Clinical and Translational Research at Einstein and Montefiore.

Learn more about headache at, home of the American Academy of Neurology's free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

When posting to social media channels about this research, we encourage you to use the hashtags #Neurology and #AANscience.

The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with over 36,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, concussion, Parkinson's disease and epilepsy.

For more information about the American Academy of Neurology, visit or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube.

Media Contacts:

Renee Tessman,, (612) 928-6137

M.A. Rosko,, (612) 928-6169

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.