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

BMJ 2003; 327 doi: (Published 25 September 2003) Cite this as: BMJ 2003;327:708
  1. TREC Collaborative Group
  1. Correspondence to: G Huf, Universidade Federal do Rio de Janeiro, Núcleo de Estudos de Saúde Coletiva, Av. Brigadeiro Trompowsky s/n, Edifício Hospital Universitário 5 andar, ala sul - Ilha do Fundão, Rio de Janeiro, Brazil, 21941-590, Caixa Postal 68037 gisele{at}
  • Accepted 10 July 2003


Abstract 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.


  • Contributors GH, ESFC, and CEA had the idea for the study and led the development of the protocol, securing of funding, study administration, data analysis, interpretation of results, and writing of the paper. RVSB, MAVF, FJFS, AJCRP, MPCPS, MG, WL, FMA, SML, VRPM, and CLD contributed to collection of data and quality control of data collection. GH, ESFC, CEA are guarantors for the study.

  • Funding No participating centre directly received funds for involvement in TREC. GH undertook TREC as part of her work funded by the Ministry of Health, Brazil. TREC was jointly funded by Fundação Osvaldo Cruz, the Cochrane Schizophrenia Group, the British Council, CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and FAPERJ (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro). All salary funding was intramural. Drugs used in the trial were supplied by the local government through Secretaria Municipal de Saúde do Rio de Janeiro. A computer was given by the Resource Centre for Randomised Controlled Trials (

  • Competing interests None declared

  • Ethical approval TREC was approved by ethics committees from Escola Nacional de Saúde Pública Fundação Oswaldo Cruz, Instituto Phillipe Pinel, and Hospital Municipal Jurandyr Manfredini, Instituto Municipal de Assistência à Saúde Nise da Silveira and by the members of the Consumer Advocate Group of Rio de Janeiro (SOSINTRA–Society of family and friends of the mentally ill in Rio de Janeiro). TREC was also approved by the National Council of Ethics in Research.

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