Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department

Acad Emerg Med. 2021 Apr;28(4):421-434. doi: 10.1111/acem.14124. Epub 2020 Oct 5.


Background: The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and safety of intramuscular droperidol, ziprasidone, and lorazepam for acute agitation in the ED.

Methods: This was a randomized, double-blind trial of ED patients with acute agitation requiring parenteral sedation. The study was conducted under exception from informed consent (21 CFR 50.24) from July 2004 to March 2005. Patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. We recorded Altered Mental Status Scale (AMSS) scores, nasal end-tidal carbon dioxide (ETCO2 ), and pulse oximetry (SpO2 ) at 0, 15, 30, 45, 60, 90, and 120 minutes as well as QTc durations and dysrhythmias. Respiratory depression was defined as a change in ETCO2 consistent with respiratory depression or SpO2 < 90%. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes.

Results: We enrolled 115 patients. Baseline AMSS scores were similar between groups. For the primary outcome, adequate sedation at 15 minutes, droperidol administration was effective in 16 of 25 (64%) patients, compared to seven of 28 (25%) for 10 mg of ziprasidone, 11 of 31 (35%) for 20 mg of ziprasidone, and nine of 31 (29%) for lorazepam. Pairwise comparisons revealed that droperidol was more effective that the other medications, with 39% (95% confidence interval [CI] = 3% to 54%) more compared to 20 mg of ziprasidone and 33% (95% CI = 8% to 58%) more compared to lorazepam. There was no significant difference between groups in need of additional rescue sedation. Numerically, respiratory depression was lower with droperidol (3/25 [12%]) compared to 10 mg of ziprasidone (10/28 [36%]), 20 mg of ziprasidone (12/31 [39%]), or lorazepam (15/31 [48%]). One patient receiving 20 mg of ziprasidone required intubation to manage an acute subdural hematoma. No patients had ventricular dysrhythmias. QTc durations were similar in all groups.

Conclusions: Droperidol was more effective than lorazepam or either dose of ziprasidone for the treatment of acute agitation in the ED and caused fewer episodes of respiratory depression.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antipsychotic Agents* / adverse effects
  • Droperidol* / adverse effects
  • Emergency Service, Hospital
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Injections, Intramuscular
  • Lorazepam / adverse effects
  • Piperazines
  • Psychomotor Agitation / drug therapy
  • Thiazoles


  • Antipsychotic Agents
  • Hypnotics and Sedatives
  • Piperazines
  • Thiazoles
  • ziprasidone
  • Lorazepam
  • Droperidol