Bronx, NY—Moderate-to-severe headaches aren’t uncommon even weeks after a head injury leading to concussion. Sometimes the pain can linger even longer.

A new study advises that a combination of two drugs, both common antinausea medications, can provide significant relief, however, if administered IV during emergency care.

The report published online by Neurology, the medical journal of the American Academy of Neurology, recommends the use of metoclopramide, an antinausea medicine sometimes used to treat migraine, and diphenhydramine, a common antihistamine that when used in its injected form can treat motion sickness.

The combination was used because higher doses of metoclopramide given IV can cause restlessness, according to Albert Einstein College of Medicine–led researchers.

“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 lead author Benjamin W. Friedman, MD.

The randomized, double blind, placebo-controlled, parallel group study in two urban emergency departments (EDs) included 160 participants who experienced head trauma and presented for emergency care within 10 days with a headache fulfilling criteria for acute post-traumatic headache.

The patients were randomized in a 1:1 ratio to metoclopramide and diphenhydramine (M+D) or placebo, with participants, caregivers, and outcome assessors blinded to assignment. Improvement in pain on a 0-10 scale between baseline and 1 hour post-treatment was defined as the primary outcome for the study completed between August 2017 and March 2020.

Researchers dosed 81 patients with 20 milligrams (mg) of metoclopramide and 25 mg of diphenhydramine intravenously, while the remaining 79 participants were given an injection of saline solution as a placebo. According to the results, placebo patients reported mean improvement of 3.8 (SD 2.6) while those on the drug combination improved by 5.2 (SD 2.3), for a difference favoring metoclopramide of 1.4 (95% CI, 0.7, 2.2, P <.01).

Adverse events, mainly drowsiness, restlessness, or gastrointestinal upset, were reported by 35/81 (43%) of patients who received metoclopramide and 22/79 (28%) of patients who received placebo (95% CI for difference of 15%: 1, 30%, P = .04), according to the report.

“Metoclopramide + diphenhydramine was more efficacious than placebo with regard to relief of post-traumatic headache in the ED,” the authors conclude, adding, “This study provides Class I evidence that for patients with acute moderate or severe post-traumatic headache, IV metoclopramide + diphenhydramine significantly improved pain compared to placebo.”

The study determined that the drug combination reduced the average patient’s pain level by more than five points on a 1-10 scale withing an hour. Reports from participants receiving the combination of metoclopramide and diphenhydramine note improvement, on average, by 5.2 points on the pain scale. Those in the group given a placebo, on average, said their pain improved by 3.8 points on the pain scale.

“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,” Dr. 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.”

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