McCoy JJ, Aldy K, Arnall E, et al. Treatment of Headache in the Emergency Department: Haloperidol in the Acute Setting (THE-HA Study): A Randomized Clinical Trial.
Headache is one of the most common ED complaints, and the standard cocktail (NSAIDs, metoclopramide, diphenhydramine) leaves a meaningful fraction of patients under-treated with long lengths of stay.
Dopamine antagonists for headache aren't new — droperidol and prochlorperazine both have prior positive RCT data in this space, and even haloperidol itself had already been shown roughly equivalent to metoclopramide (Gaffigan et al., 2015) and effective as migraine rescue therapy (Honkaniemi et al., 2006) before this trial. What THE-HA Study adds is the first RCT testing a reduced 2.5 mg IV dose specifically, in a broader "undifferentiated benign headache" population rather than migraine-only, without routine diphenhydramine pretreatment.
| Design | Single-center, randomized, double-blind, placebo-controlled trial |
| Population | 287 screened; 118 enrolled, ages 13–55, acute benign headache |
| Groups | 58 received 2.5 mg IV haloperidol; 60 received 5 mL 0.9% saline placebo |
| Primary outcome | Pain reduction (VAS) at 60 minutes |
| Monitoring | VAS and vitals at 30, 60, 90 minutes; QTc at baseline and discharge |
| Exclusions | BP >200/100, sudden/thunderclap onset, fever or altered mental status, acute trauma, history of brain mass/stroke or abnormal intracranial anatomy, abnormal neuro exam, pregnancy, incarceration — a standard secondary-headache red-flag screen |
| Outcome | Haloperidol | Placebo | P value |
|---|---|---|---|
| >50% pain relief at 30 min | 20 (34.5%) | 7 (11.7%) | 0.003 |
| >50% pain relief at 60 min | 37 (63.8%) | 13 (21.7%) | <0.0001 |
| QTc change at discharge | Not statistically or clinically significant | ||
| 24-hour follow-up | Haloperidol | Placebo |
|---|---|---|
| Reported side effects | 8 (14.6%) | 4 (7%) |
| Would request haloperidol again | 44 (75.9%) | 21 (35%) |
| Return of symptoms | 18 (32.7%) | 29 (50.9%) |
Every figure on the REBEL EM card matches the published paper. Worth pulling out because it's easy to skim past on the infographic: the benefit wasn't just faster acute relief — the haloperidol group also had a lower rate of headache recurrence at 24 hours (32.7% vs. 50.9%), which is a durability signal, not just a speed signal.
This is worth catching before it becomes a protocol.
The infographic's clinical question and methods both correctly state the trial enrolled patients 13 to 55 years old. But REBEL EM's own conclusion box recommends the treatment "in patients b/w ages of 18–55" — narrower than what was actually studied. This isn't a REBEL EM error so much as a faithful carry-through of the original authors' own hedge: the published paper's conclusion explicitly states adolescent results need further confirmation, implying the 13–17 subgroup wasn't independently powered or fully reassuring on its own. If you're building a protocol off this infographic, don't extend it to adolescents based on the trial's inclusion criteria alone — the authors and REBEL EM both stop at 18 for a reason that isn't fully spelled out in the card.
2.5 mg is half the typical prior study dose, and that's not incidental to the results.
Most prior ED haloperidol-for-headache literature used 5 mg with routine diphenhydramine pretreatment to blunt extrapyramidal side effects. THE-HA Study's authors specifically attribute their low observed rates of akathisia and sedation — and the fact that somnolence wasn't observed at all — to the halved 2.5 mg dose, concluding that routine diphenhydramine pretreatment may be unnecessary at this dose. That's a meaningful practice point the infographic's side-effect row (14.6% vs. 7%, "uncommon, benign, easily treated") doesn't fully unpack: the low side-effect rate isn't just a lucky result, it's a direct consequence of the dose-reduction design choice.
The REBEL EM infographic is accurate on every number and appropriately restrained in its conclusion (18–55, not the full 13–55 enrolled range). This adds two things worth carrying into practice: first, low-dose (2.5 mg) IV haloperidol for undifferentiated benign headache isn't an isolated finding — it extends a decade-plus of positive dopamine-antagonist headache trials, with the dose reduction itself likely explaining the low side-effect burden. Second, don't extrapolate to adolescents on the strength of the trial's inclusion criteria; both the original authors and REBEL EM's own conclusion box are more conservative than the enrollment range would suggest, and that's worth respecting rather than smoothing over.