Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine

BMJ. 2003 Sep 27;327(7417):708-13. doi: 10.1136/bmj.327.7417.708.


Objective: To compare two widely used drug treatments for people with aggression or agitation due to mental illness.

Design: Pragmatic, randomised clinical trial.

Setting: Three psychiatric emergency rooms in Rio de Janeiro, Brazil.

Subjects: 301 aggressive or agitated people.

Interventions: Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine.

Main outcome measures: Patients tranquil or sedated at 20 minutes.

Secondary outcomes: patients tranquil or asleep by 40, 60, and 120 minutes; restrained or given extra drugs within 2 hours; severe adverse events; another episode of agitation or aggression; needing extra visits from doctor during first 24 hours; overall antipsychotic load in first 24 hours; and not discharged by two weeks.

Results: 151 patients were randomised to midazolam, and 150 to haloperidol-promethazine mix. Follow up for the primary outcome was available for 298 (99%): 134/151 (89%) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 (67%) of those given haloperidol plus promethazine (relative risk 1.32 (95% confidence interval 1.16 to 1.49)). By 40 minutes, midazolam still had a statistically and clinically significant 13% relative advantage (1.13 (1.01 to 1.26)). After 1 hour, about 90% of both groups were tranquil or asleep. One important adverse event occurred in each group: a patient given midazolam had transient respiratory depression, and one given haloperidol-promethazine had a grande mal seizure.

Conclusions: Both treatments were effective. Midazolam was more rapidly sedating than haloperidol-promethazine, reducing the time people are exposed to aggression. Adverse effects and resources to deal with them should be considered in the choice of the treatment.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aggression*
  • Drug Therapy, Combination
  • Emergency Service, Hospital
  • Emergency Services, Psychiatric
  • Emergency Treatment / methods
  • Female
  • Haloperidol / administration & dosage*
  • Haloperidol / adverse effects
  • Hospitals, Psychiatric
  • Humans
  • Injections, Intramuscular
  • Male
  • Mental Disorders / psychology*
  • Midazolam / administration & dosage*
  • Midazolam / adverse effects
  • Promethazine / administration & dosage*
  • Promethazine / adverse effects
  • Psychomotor Agitation / drug therapy*
  • Psychomotor Agitation / psychology
  • Restraint, Physical
  • Sleep
  • Tranquilizing Agents / administration & dosage*
  • Tranquilizing Agents / adverse effects
  • Treatment Outcome


  • Tranquilizing Agents
  • Promethazine
  • Haloperidol
  • Midazolam