Combination treatment improves pain scores for post-traumatic headache in ED
Click Here to Manage Email Alerts
Metoclopramide plus diphenhydramine resulted in greater improvement in pain scores compared with placebo for patients with acute post-traumatic headache in the ED, according to findings from a parallel group study published in Neurology.
“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,” Benjamin W. Friedman, MD, MS, FAAEM, FACEP, FAHS, professor of emergency medicine and vice chair for clinical investigation in the department of emergency medicine at Albert Einstein College of Medicine and Montefiore Medical Center, said in a press release.
Friedman and colleagues conducted the present investigation — a randomized, double-blind, placebo-controlled, parallel group study in two urban EDs — because of a “huge unmet need” in this area, he told Healio Neurology.
The study, which took place between August 2017 and March 2020, included participants with head trauma who presented to the ED within 10 days of the event and met criteria for acute post-traumatic headache. Researchers randomly assigned patients 1:1 to receive either IV metoclopramide 20 mg plus diphenhydramine 25 mg or placebo. Improvement in pain according to a scale of zero to 10 from baseline to 1 hour after treatment served as the primary outcome.
Researchers screened 414 patients and randomly assigned 160 of these individuals, including 81 to metoclopramide plus diphenhydramine and 79 to placebo. The study population included mostly women, with similar baseline characteristics between the two groups. Approximately one-quarter of participants reported a preexisting headache disorder, according to the study results. All participants provided data related to the primary outcome.
Patients who received placebo reported a mean improvement of 3.8 compared with a mean improvement of 5.2 among patients who received metoclopramide plus diphenhydramine. This represented a difference in favor of metoclopramide of 1.4 (95% CI, 0.7-2.2), according to the findings from Friedman and colleagues.
“We knew these medications work for migraine and tension-type headache,” Friedman said. “Since many post-traumatic headaches take the form of either migraine or tension-type headache, we thought it might work for these as well.”
In addition to the greater effectiveness for both headache and post-concussive symptoms, researchers found that the benefits of metoclopramide plus diphenhydramine “lingered” for post-concussive symptoms, according to Friedman. That lingering effect was not observed for headache. Researchers were surprised to find that the benefits for post-concussive symptoms persisted for up to 1 week, he said.
The treatment resulted in “a lot of nuisance side effects,” according to Friedman, including drowsiness among 15 treated patients and eight placebo patients, akathisia among five treated patients, dizziness among four treated patients and one placebo patient, diarrhea among two treated patients and one placebo patient, and reports of symptoms consistent with post-concussive syndrome among seven treated patients and five placebo patients. No more than two participants reported any other symptoms, and there were no serious or unexpected adverse events, according to the study results. Altogether, adverse events were reported by 43% of patients who received metoclopramide plus diphenhydramine and 28% of patients who received placebo (P = .04).
The researchers plan to expand the benefits of metoclopramide plus diphenhydramine to the post-ED period and reduce side effects, he said.
“Future work should determine the optimal dose and duration of treatment with metoclopramide targeted at longer-term outcomes beyond the ED visit. Also, future work can determine whether early treatment can impact other post-concussive symptoms such as depression, sleep disorders and anxiety, which negatively impact the lives of many patients with post-traumatic headache,” the researchers wrote. “Comparative effectiveness studies could compare metoclopramide to non-steroidal anti-inflammatory drugs or migraine-specific medication such as triptans. Case reports indicate that corticosteroids may be efficacious for acute post-traumatic headache.”