Intended for healthcare professionals


Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine

BMJ 2007; 335 doi: (Published 25 October 2007) Cite this as: BMJ 2007;335:869
  1. Gisele Huf, associate professor1,
  2. E S F Coutinho, professor2,
  3. C E Adams, associate professor3
  4. TREC Collaborative Group
  1. 1National Institute of Quality Control in Health (INCQS), Oswaldo Cruz Foundation (FIOCRUZ), Av Brasil 4365, Manguinhos, 21040-900, Rio de Janeiro, Brazil
  2. 2National School of Public Health (ENSP), Oswaldo Cruz Foundation (FIOCRUZ)
  3. 3Division of Psychiatry, University of Nottingham, Nottingham
  1. Correspondence to: G Huf gisele{at}
  • Accepted 4 September 2007


Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine.

Design Pragmatic randomised open trial (January-July 2004).

Setting Psychiatric emergency room, Rio de Janeiro, Brazil.

Participants 316 patients who needed urgent intramuscular sedation because of agitation, dangerous behaviour, or both.

Interventions Open treatment with intramuscular haloperidol 5-10 mg or intramuscular haloperidol 5-10 mg plus intramuscular promethazine up to 50 mg; doses were at the discretion of the prescribing clinician.

Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes. Secondary outcomes were asleep by 20 minutes; tranquil or asleep by 40, 60, and 120 minutes; physically restrained or given additional drugs within 2 hours; severe adverse events; another episode of agitation or aggression; additional visit from the doctor during the subsequent 24 hours; overall antipsychotic load in the first 24 hours; and still in hospital after 2 weeks.

Results Primary outcome data were available for 311 (98.4%) people, 77% of whom were thought to have a psychotic illness. Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone (relative risk 1.30, 95% confidence interval 1.10 to 1.55; number needed to treat 6, 95% confidence interval 4 to 16; P=0.002). No differences were found after 20 minutes. However, 10 cases of acute dystonia occurred, all in the haloperidol alone group.

Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety. Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects.

Trial registration Current Controlled Trials ISRCTN83261243.


  • We thank the medical, nursing, and pharmacy staff of Institute P Pinel, Rio de Janeiro, for their kindness, patience, interest, and enthusiasm. We also thank Gill Rizzello and Lelia Duley for comments on the manuscript. Gisele Gadret Mendes Diniz provided data for total emergency attendances at the hospital.

  • Contributors: GH was involved in study concept and design; acquisition, analysis, and interpretation of data; and drafting the manuscript. ESFC and CEA were involved in study concept and design, analysis and interpretation of data, and drafting the manuscript. The TREC Collaborative Group was involved in data acquisition and critical revision of the manuscript. GH is the guarantor.

    Members of the TREC Collaborative Group: Alexandre Luiz G S Martins, André J C R Pereira, Angela Cristina de Souza Amorim, Eduardo da Silveira Martins, Francisco J F Silva, Heimar Saldanha Camarinha, Marco Antonio de Vilhena Ferreira, Marcos Micelli, Nilcilene Maximiano, Raul V S Borges, Ricardo Lugon, Sílvia Pereira.

    Data Monitoring Committee: Claudio Jose Struchiner (chair), Luiz Antonio Bastos Camacho, José Ramon Rodrigues Arras Lopez.

    Trial Steering Committee: Marco Antonio Brasil (chair), Gisele Huf, Evandro S F Coutinho, Clive E Adams, Suely Rozenfeld, Jair de Jesus Mari.

    Funding: Brazilian Research Council (CNPq).

  • Competing interests: None declared.

  • Ethical approval: Ethics committees from Escola Nacional de Saúde Pública Fundação Oswaldo Cruz, Instituto Phillipe Pinel; 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); National Council of Ethics in Research, Brazil.

    Provenance and peer review: Not commissioned; externally peer reviewed.

  • Accepted 4 September 2007
View Full Text