Hostname: page-component-848d4c4894-4hhp2 Total loading time: 0 Render date: 2024-06-13T01:20:53.971Z Has data issue: false hasContentIssue false

Establishing gold standard approaches to rapid tranquillisation: A review and discussion of the evidence on the safety and efficacy of medications currently used

Published online by Cambridge University Press:  01 December 2008

J Peter Pratt
Chief Pharmacist, Sheffield Care Trust
Jacqueline Chandler-Oatts*
Research Fellow, Royal College of Nursing Research Institute, Warwick University
Louise Nelstrop
Research Fellow, Royal College of Nursing Institute, Oxford
Dave Branford
Chief Pharmacist Derbyshire Mental Health Services NHS Trust
Stephen Pereira
Consultant Psychiatrist, North East London Mental Health Trust
Susan Johnston
Consultant Psychiatrist, Rampton Hospital, Nottinghamshire Healthcare NHS Trust
Correspondence to: J. Chandler-Oatts, Royal College of Nursing Research Institute at Warwick University, Whichford House, Oxford Business Park, Oxford, 0X4 2JY, UK. Tel: +44 (0) 1865 787115; Fax: +44 (0) 1865 787149; E-mail:
Get access


Background: Rapid tranquillisation is used when control of agitation, aggression or excitement is required. Throughout the UK there is no consensus over the choice of drugs to be used as first line treatment. The NICE guideline on the management of violent behaviour involving psychiatric inpatients conducted a systematic examination of the literature relating to the effectiveness and safety of rapid tranquillisation (NICE, 2005). This paper presents the key findings from that review and key guideline recommendations generated, and discusses the implications for practice of more recent research and information.

Aims: To examine the evidence on the efficacy and safety of medications used for rapid tranquillisation in inpatient psychiatric settings.

Method: Systematic review of current guidelines and phase III randomised, controlled trials of medication used for rapid tranquillisation. Formal consensus methods were used to generate clinically relevant recommendations to support safe and effective prescribing of rapid tranquillisation in the development of a NICE guideline.

Findings: There is a lack of high quality clinical trial evidence in the UK and therefore a ‘gold standard’ medication regime for rapid tranquillisation has not been established.

Rapid tranquillisation and clinical practice: The NICE guideline produced 35 recommendations on rapid tranquillisation practice for the UK, with the primary aim of calming the service user to enable the use of psychosocial techniques.

Conclusions and implications for clinical practice: Further UK specific research is urgently needed that provides the clinician with a hierarchy of options for the clinical practice of rapid tranquillisation.

Review Article
Copyright © NAPICU 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Aleman, A. and Kahn, R.S. (2001) Effects of the atypical antipsychotic risperidone on hostility and aggression in schizophrenia: A meta-analysis of controlled trials. European Neuropsychopharmacology. 11: 289293.CrossRefGoogle ScholarPubMed
Alexander, J., Tharyan, P., Adams, C., John, T., Mol, C. and Philip, J. (2004) Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam versus haloperidol plus promethazine. British Journal of Psychiatry. 185: 6369.CrossRefGoogle ScholarPubMed
Battaglia, J., Moss, S., Rush, J., Kang, J., Mendoza, R., Leedom, L., Dubin, W., McGlynn, C. and Goodman, L. (1997) Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective double-blind, emergency department study. American Journal of Emergency Medicine. 15(4): 335340.CrossRefGoogle ScholarPubMed
Beer, M.D., Paton, C. and Pereira, S.M. (2001) Management of acutely disturbed behaviour. In: Beer, M.D, Pereira, S.M., Paton, C. (eds). Psychiatric Intensive Care. London: Greenwich Medical Media. p.25.Google Scholar
Bieniek, S.A., Ownby, R.L., Penalver, A., and Domingues, R.A. (1998) A double-blinded study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Pharmacotherapy. 18: 5762.CrossRefGoogle ScholarPubMed
Binder, R.L. and McNiel, D.E. (1999) Contemporary practices in managing acutely violent patients in 20 psychiatric emergency rooms. Psychiatric Services. 50(12): 15531554.CrossRefGoogle ScholarPubMed
Brier, A., Meehan, K., Birkett, M., David, S., Ferchland, I., Sutton, V., Taylor, C.C., Palmer, R., Dossenbach, M., Kiesler, G., Brook, S. and Wright, P. (2002) A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Archive of General Psychiatry. 59: 441448.CrossRefGoogle Scholar
Broadstock, M. (2001) The Effectiveness and Safety of Drug Treatment for Urgent Sedation in Psychiatric Emergencies: A Critical Appraisal of the Literature. New Zealand Health Technology Assessment Report 2001; 4(1).Google Scholar
Brook, S., Lucey, J.V. and Gunn, K.P. (2000) Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Journal of Clinical Psychiatry. 61(12):933941.CrossRefGoogle ScholarPubMed
Burgess, S. (1997) Emergency drug treatment of disturbed psychotic patients. Auditorium. 6(1):2830.Google Scholar
Corrigan, J.D. (1989) Development of a scale of assessment of agitation following traumatic brain injury. Journal of Clinical and Experimental Neuropsychology. 11(2): 261277.CrossRefGoogle ScholarPubMed
Cunnane, J.G. (1994) Drug management of disturbed behaviour by psychiatrists. Psychiatric Bulletin. 18: 138139.CrossRefGoogle Scholar
Day, C.P., James, O.F.W., Butler, T.J., and Campbell, R.W.F. (1993) QT prolongation and sudden death in patients with alcoholic liver disease. Lancet. 341:14231428.Google ScholarPubMed
Dorevitch, A., Katz, N., Zemishlany, Z., Aizenberg, D. and Weizman, A. (1999) Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. American Journal of Psychiatry. 156(1): 142144.CrossRefGoogle ScholarPubMed
Drake, W.M., and Broadhurst, P.A. (1996) QT-interval prolongation with ecstasy. South African Medical Journal. 86: 180181.Google ScholarPubMed
Drici, M.D., Wang, W.X., Li, X., Woosley, R.L. and Flockhart, D.A. (1998) Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. Journal of Clinical Psychopharmacology. 18: 477481.CrossRefGoogle ScholarPubMed
Eccles, M. and Mason, J. (2001) How to Develop Cost Conscious Guidelines. Health Technology Assessment; 5(16). London: NICE.CrossRefGoogle ScholarPubMed
Foster, S., Kessel, J., Berman, M.E. and Simpson, G.M. (1997) Efficacy of lorazepam and haloperidol for rapid tranquillisation in a psychiatric emergency room setting. International Clinical Psychopharmacology. 12(3):175179.CrossRefGoogle Scholar
Fruensgaard, K., Karsgaard, S., Jøgenson, H. and Jenson, K. (1977) Loxapine versus haloperidol parenterally in acute psychosis with agitation. Acta Psychiatrica Scandanavia. 56: 256264.CrossRefGoogle ScholarPubMed
Garza-Trevino, E.S., Hollister, L.E., Overall, J.E. and Alexander, W.F. (1989) Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. American Journal of Psychiatry. 146(12): 15981601.Google ScholarPubMed
Gibson, R.C., Fenton, M., da Silva Freire Coutinho, E. and Campbell, C. (2000) Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses. Cochrane Database of Systematic Reviews 2000, Issue 1. Art. No.: CD000525. DOI: 10.1002/14651858.CD000525.pub2CrossRefGoogle Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopathology. Rockville, MD: Department of Health Education and Welfare, National Institute of Mental Health. pp. 217–222.Google Scholar
Holmes, C., Simmons, H. and Pilowsky, L. (2001) Rapid tranquillisation. In: Beer, M.D, Pereira, S.M., Paton, C. (eds). Psychiatric Intensive Care. London: Greenwich Medical Media. p.47.Google Scholar
Huf, G., Alexander, J. and Allen, M.H. (2004) Haloperidol and promethazine for psychosis induced aggression. Cochrane Database of Systematic Reviews. 2004, Issue 4. Art no: CD005146.DOI: 10.1002/14651858.CD005146.CrossRefGoogle Scholar
Huf, G., Coutinho, E.S.F., Adams, C.E. and TREC Collaborative Group (2007) Rapid tranquillisation in psychiatric emergency settings in Brazil: Pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol and promethazine. British Medical Journal. 335: 869.CrossRefGoogle ScholarPubMed
Kay, S.R., Fiszbein, A. and Opler, L.A. (1992) Positive and Negative Syndrome Scale (PANSS) Manual. Toronto: Multi-Health Systems.Google Scholar
Makkar, R.R., Fromm, B.S., Steinman, R.T., Meissner, M.D. and Lehmann, M.H. (1993) Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. Journal of the American Medical Association. 270(21):25902597.CrossRefGoogle ScholarPubMed
Mason, J., Nicolson, D., and Wilson, D. (2002) Systematic review methods for national guidelines. Unpublished discussion paper.Google Scholar
McAllistair-Williams, R.H. and Ferrier, I.N. (2002) Rapid tranquillisation: Time for a reappraisal of options for parenteral therapy. British Journal of Psychiatry. 180: 485489.CrossRefGoogle Scholar
National Collaborating Centre for Mental Health (2002) Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care. London: NICE. Scholar
NICE (2005) Clinical Guideline 25. Violence: The Short-Term Management of Disturbed/Violent Behaviour in Psychiatric In-Patient Settings and Emergency Departments. London: NICE. Scholar
NICE Technical Manual (2004) Guideline Development Methods: Information for National Collaborating Centres and Guideline Developers. London: NICE.Google Scholar
Overall, J. and Gorham, P. (1962) The Brief Psychiatric Rating Scale. Psychology Reports. 22: 788812.Google Scholar
Paprocki, J. and Versiani, M. (1977) A double blinded comparison between loxapine and haloperidol by parenteral route in acute schizophrenia. Current Therapeutic Research. 21(1):80100.Google Scholar
Pereira, R., Kraebber, A., and Schwartz, M. (1997) Prolonged QT interval and cocaine use. Journal of Electrocardiology. 30: 337339.CrossRefGoogle Scholar
Rautaharju, P., Zhou, S.H., Wong, S., Calhoun, H.P., Berenson, G.S., Prineas, R. and Davignon, A. (1992) Sex differences in the evolution of the electrocardiographic QT interval with age. Canadian Journal of Cardiology. 8: 690695.Google ScholarPubMed
Raveendran, N.S., Tharyan, P., Alexander, J. and Elliot, C. (2007) Rapid tranquillisation in psychiatric emergency settings in India: Pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine. British Medical Journal. 335: 865.CrossRefGoogle ScholarPubMed
Ray, W.A., Meredith, S., Thapa, P.B., Meador, K.G., Hall, K. and Murray, K.T. (2001) Antipsychotics and the risk of sudden cardiac death. Archives of General Psychiatry. 58: 11611167.CrossRefGoogle ScholarPubMed
Reilly, J.R. (2000) QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. The Lancet. 355(35): 10481052.CrossRefGoogle ScholarPubMed
Reschke, R.W. (1974) Parenteral haloperidol for rapid control of severe, disruptive symptoms of acute schizophrenia. Diseases of the Nervous System. 35(3):112115.Google ScholarPubMed
Royal College of Nursing (2005) Violence: The Short Term Management of Disturbed/Violent Behaviour in In-Patient Psychiatric Settings and Emergency Departments. London: RCN. Scholar
Royal College of Psychiatrists (1997) The Association Between Antipsychotic Drugs and Sudden Death: Report of the Working Group of the Royal College of Psychiatrists' Psychopharmacology Sub-Group. Council Report CR57. London: Royal College of Psychiatrists.Google Scholar
Royal College of Psychiatrists (1998) Management of Imminent Violence: Clinical Practice Guidelines to Support Mental Health Services. OP41. London: Royal College of Psychiatrists.Google Scholar
TREC Collaborative Group (2003) Rapid tranquillisation for agitated patients in emergency psychiatric rooms: A randomised trial of midazolam versus haloperidol plus promethazine. British Medical Journal. 327: 708713.CrossRefGoogle Scholar
Tuason, V.B. (1986) A comparison of parenteral loxapine and haloperidol in hostile and aggressive acutely schizophrenic patients. Journal of Clinical Psychiatry. 47: 126129.Google ScholarPubMed
Warner, J.P., Barnes, T.R.E. and Henry, J.A. (1996) Electrocardiographic changes in patients receiving neuroleptic medication. Acta Psychiatrica Scandinavica. 93: 311313.CrossRefGoogle ScholarPubMed
Wright, P., Birkett, M., David, S.R., Meehan, K., Ferchland, I., Alaka, K.J., Saunders, J.C., Kreuger, J., Bradley, P., San, L., Bernardo, M., Reinstein, M. and Brier, A. (2001) Double-blind, placebo-controlled comparison of intramusclar olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. American Journal of Psychiatry. 158(7):11491151.CrossRefGoogle Scholar
Wright, S., Gray, R., Parkes, J. and Gournay, K. (2002) The Recognition, Prevention and Therapeutic Management of Violence in Acute In-Patient Psychiatry: A Literature Review and Evidence-Based Recommendations for Good Practice. London: United Kingdom Central Council for Nursing, Midwifery and Health Visiting.Google Scholar
Wyant, M., Diamond, B.I., O'Neal, E., Sloan, A. and Borison, R.L. (1990) The use of midazolam in acutely agitated psychiatric patients. Psychopharmacology Bulletin. 26(1): 126129.Google ScholarPubMed
Yudofsky, S.C., Kopecky, H.J., Kunik, M., Silver, J.M., and Endicott, J. (1997) The overt agitation severity scale for the objective rating of agitation. Journal of Neuropsychiatry and Clinical Neuroscience. 9(4):541548.Google ScholarPubMed