Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Nov 27;11(11):CD009830.
doi: 10.1002/14651858.CD009830.pub2.

Haloperidol for long-term aggression in psychosis

Abha Khushu  1 , Melanie J Powney
Affiliations

Haloperidol for long-term aggression in psychosis

Abha Khushu et al. Cochrane Database Syst Rev. .

Abstract

Background: Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression.

Objectives: To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis.

Search methods: We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015).

Selection criteria: We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression.

Data collection and analysis: One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.

Main results: We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study (1 RCT, n=110, RR 1.37, CI 0.84 to 2.24, low-quality evidence). Although there were some data for the outcomes listed above, there were no data on most of the binary outcomes and none on service outcomes (use of hospital/police), satisfaction with treatment, acceptance of treatment, quality of life or economics.

Authors' conclusions: Only one study could be included and most data were heavily skewed, almost impossible to interpret and oflow quality. There were also some limitations in the study design with unclear description of allocation concealment and high risk of bias for selective reporting, so no firm conclusions can be made. This review shows how trials in this group of people are possible - albeit difficult. Further relevant trials are needed to evaluate use of haloperidol in treatment of long-term/persistent aggression in people living with psychosis.

PubMed Disclaimer

Conflict of interest statement

AK: none known.

MP: none known.

Figures

1
1
Haloperidol structure.
2
2
Study flow diagram.
3
3
Study flow diagram (pre‐submission search of 1 April 2015).
4
4
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
5
5
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3.1
3.1. Analysis
Comparison 3 HALOPERIDOL versus OTHER ANTIPSYCHOTICS, Outcome 1 Leaving the study early.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009830

References

References to studies included in this review

Krakowski 2006 {published data only}
    1. Krakowski M, Czobor P. A prospective longitudinal study of cholesterol and aggression in patients randomized to clozapine, olanzapine and haloperidol. 15th Biennial Winter Workshop in Psychoses; 2009 Nov 15‐18; Barcelona, Spain. 2009. - PubMed
    1. Krakowski M, Czobor P, Citrome L. Weight gain, metabolic parameters, and the impact of race in aggressive inpatients randomized to double‐blind clozapine, olanzapine or haloperidol. Schizophrenia Research 2009;110(1‐3):95‐102. [MEDLINE: ] - PubMed
    1. Krakowski MI. Clozapine and olanzapine in violent schizophrenics. CRISP database (www‐commons.cit.nih.gov/crisp/index.html) (accessed 19 February 2001).
    1. Krakowski MI, Czobor P. A prospective longitudinal study of cholesterol and aggression in patients randomized to clozapine, olanzapine, and haloperidol. Journal of Clinical Psychopharmacology 2010;30(2):198‐200. - PubMed
    1. Krakowski MI, Czobor P. Depression and impulsivity as pathways to violence: implications for antiaggressive treatment. Schizophrenia Bulletin 2014; Vol. 40, issue 4:886‐94. - PMC - PubMed

References to studies excluded from this review

Singh 1981 {published data only}
    1. Singh MM, Kay SR, Pitman RK. Aggression control and structuring of social relations among recently admitted schizophrenics. Psychiatry Research 1981;5(2):157‐69. [MEDLINE: ] - PubMed
Volavka 2002 {published data only}
    1. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, et al. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. American Journal of Psychiatry 2002;159(6):1018‐28. [MEDLINE: ] - PubMed
    1. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, et al. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol on treatment‐resistant patients with schizophrenia and schizoaffective disorder. European Neuropsychopharmacology 2001;11(3):256.
    1. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, et al. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol on treatment‐resistant patients with schizophrenia and schizoaffective disorder. Schizophrenia Research. Elsevier Science B.V, 2002; Vol. 53, issue 3 Suppl 1:194.
    1. Citrome L, Volavka J, Czobor P, Sheitman B, Lindenmayer JP, McEvoy J, et al. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatric Services 2001;52(11):1510‐4. [MEDLINE: ] - PubMed
    1. Citrome LL, Volavka J, Czobor P, Nolan K, Lieberman JA, Lindenmayer JP, et al. Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. 156th Annual Meeting of the American Psychiatric Association; 2003 May 17‐22; San Francisco (CA). 2003. - PubMed

References to studies awaiting assessment

Lewis 2006 {published data only}
    1. Lewis CF. Haloperidol versus risperidone in the treatment of aggressive psychotic male inmates. 159th Annual Meeting of the American Psychiatric Association; 2006 May 20‐25; Toronto, Canada. 2006.

Additional references

Adams 2013
    1. Adams CE, Bergman H, Irving CB, Lawrie S. Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2013, Issue 11. [DOI: 10.1002/14651858.CD003082.pub3; CD003082] - DOI - PMC - PubMed
Ahmed 2010
    1. Ahmed U, Jones H, Adams CE. Chlorpromazine for psychosis induced aggression or agitation. Cochrane Database of Systematic Reviews 2010, Issue 4. [DOI: 10.1002/14651858.CD007445.pub2; PUBMED: 20393959] - DOI - PubMed
Altman 1996
    1. Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996;313(7066):1200. - PMC - PubMed
APA 2004
    1. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. www.psychiatryonline.com/content.aspx?aID=45971 (accessed 3 June 2011).
Begg 1996
    1. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996;276(8):637‐9. - PubMed
Belgamwar 2005
    1. Belgamwar RB, Fenton M. Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD003729.pub2] - DOI - PMC - PubMed
Bland 1997
    1. Bland JM. Statistics notes. Trials randomised in clusters. BMJ 1997;315:600. - PMC - PubMed
Boissel 1999
    1. Boissel JP, Cucherat M, Li W, Chatellier G, Gueyffier F, Buyse M, et al. The problem of therapeutic efficacy indices. 3. Comparison of the indices and their use [Apercu sur la problematique des indices d'efficacite therapeutique, 3: comparaison des indices et utilisation. Groupe d'etude des indices d'efficacite]. Therapie 1999;54(4):405‐11. [PUBMED: 10667106] - PubMed
British National Formulary 2011
    1. Joint Formulary Committee. British National Formulary. 61. London: BMJ Group and Pharmaceutical Press, 2011.
Chakrabarti 2007
    1. Chakrabarti A, Whicher EV, Morrison M, Douglas‐Hall P. 'As required' medication regimens for seriously mentally ill people in hospital. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD003441.pub2] - DOI - PubMed
Deeks 2000
    1. Deeks J. Issues in the selection for meta‐analyses of binary data. 8th International Cochrane Colloquium; 2000 Oct 25‐28; Cape Town. 2000.
Divine 1992
    1. Divine GW, Brown JT, Frazier LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7(6):623‐9. - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315:629‐34. - PMC - PubMed
Elbourne 2002
    1. Elbourne D, Altman DG, Higgins JPT, Curtina F, Worthingtond HV, Vaile A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. - PubMed
Furukawa 2006
    1. Furukawa TA, Barbui C, Cipriani A, Brambilla P, Watanabe N. Imputing missing standard deviations in meta‐analyses can provide accurate results. Journal of Clinical Epidemiology 2006;59(7):7‐10. - PubMed
Gibson 2004
    1. Gibson RC, Fenton M, Coutinho ES, Campbell C. Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/14651858.CD000525.pub2] - DOI - PubMed
Gillies 2005
    1. Gillies D, Beck A, McCloud A, Rathbone J. Benzodiazepines for psychosis‐induced aggression or agitation. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD003079.pub2] - DOI - PubMed
Gulliford 1999
    1. Gulliford MC. Components of variance and intraclass correlations for the design of community‐based surveys and intervention studies: data from the Health Survey for England 1994. American Journal of Epidemiology 1999;149:876‐83. - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hodgins 2008
    1. Hodgins S. Violent behaviour among people with schizophrenia: a framework for investigations of causes, and effective treatment, and prevention. Philosophical Transactions of The Royal Society B Biological Sciences 2008;363(1503):2505–18. [DOI: 10.1098/rstb.2008.0034] - DOI - PMC - PubMed
Huf 2009
    1. Huf G, Alexander J, Allen MH, Raveendran NS. Haloperidol plus promethazine for psychosis‐induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD005146] - DOI - PubMed
Kay 1986
    1. Kay SR, Opler LA, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Manual. North Tonawanda, NY: Multi‐Health Systems, 1986.
Krakowski 2001
    1. Krakowski MI. Clozapine and olanzapine in violent schizophrenics. CRISP database (www‐commons.cit.nih.gov/crisp/index.html) (accessed 19 February 2001).
Leucht 2005a
    1. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean?. Schizophrenia Research 2005;79(2‐3):231‐8. [PUBMED: 15982856] - PubMed
Leucht 2005b
    1. Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel R. Clinical implications of Brief Psychiatric Rating Scale scores. British Journal of Psychiatry 2005;187:366‐71. [PUBMED: 16199797] - PubMed
Leucht 2007
    1. Leucht S, Engel RR, Bauml J, Davis JM. Is the superior efficacy of new generation antipsychotics an artifact of LOCF?. Schizophrenia Bulletin 2007;33(1):183‐91. [PUBMED: 16905632] - PMC - PubMed
López‐Munoz 2009
    1. López‐Munoz F, Alamo C. The consolidation of neuroleptic therapy: Janssen, the discovery of haloperidol and its introduction into clinical practice. Brain Research Bulletin 2009;79:130‐41. - PubMed
Marshall 2000
    1. Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. British Journal of Psychiatry 2000;176:249‐52. - PubMed
Moher 2001
    1. Moher D, Schulz KF, Altman D, CONSORT Group. The CONSORT statement: revised recommendations for improving the quality of reports of parallel‐group randomized trials. JAMA 2001;285:1987‐91. - PubMed
Mohr 2005
    1. Mohr P, Pecenak J, Svestka J, Swingler D, Treuer T. Treatment of acute agitation in psychotic disorders. Neuro endocrinology Letters 2005;26(4):327‐35. [PUBMED: 16136016] - PubMed
Muralidharan 2006
    1. Muralidharan S, Fenton M. Containment strategies for people with serious mental illness. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD002084.pub2] - DOI - PMC - PubMed
NICE 2005
    1. National Institute for Clinical Excellence. The Short‐Term Management of Disturbed/Violent Behaviour in Inpatient Psychiatric Settings and Emergency Departments. Vol. 25, London: NICE, 2005. - PubMed
Overall 1962
    1. Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychological Reports 1962;10:799‐812.
Powney 2011
    1. Powney MJ, Adams CE, Jones H. Haloperidol (rapid tranquilisation) for psychosis induced aggression or agitation. Cochrane Database of Systematic Reviews 2011, Issue 10. [DOI: 10.1002/14651858.CD009377] - DOI - PubMed
Pratt 2008
    1. Pratt P, Chandler‐Oatts J, Nelstrop L, Branford D, Periera S, Johnston S. Establishing gold standard approaches to rapid tranquillisation: a review and discussion of the evidence of the safety and efficacy of medications used. Journal of Psychiatric Intensive Care 2008;4(1‐2):43‐57.
Psychotropics 2003
    1. The Lundbeck Institute. Psychotropics. www.psychotropics.dk/moleculeView/default.aspx (accessed 24 December 2012).
RevMan 2012 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Sailas 2000
    1. Sailas E, Fenton M. Seclusion and restraint for people with serious mental illnesses. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD001163] - DOI - PMC - PubMed
Schleifer 2011
    1. Schleifer JJ. Management of acute agitation in psychosis: an evidence‐based approach in the USA. Advances in Psychiatric Treatment 2011;17:91‐100.
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011:359‐83.
Ukoumunne 1999
    1. Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ. Methods for evaluating area‐wide and organisation‐based intervention in health and health care: a systematic review. Health Technology Assessment 1999;3(5):1‐75. - PubMed
Xia 2009
    1. Xia J, Adams CE, Bhagat N, Bhagat V, Bhoopathi P, El‐Sayeh H, et al. Loss to outcomes stakeholder survey: the LOSS study. Psychiatric Bulletin 2009;33(7):254‐7.
Xiberas 2001
    1. Xiberas X, Martinot JL, Mallet L, Artiges E, Loc'h C, Maziere B, et al. Extrastriatal and striatal D2 dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. British Journal of Psychiatry 2001;179:503‐8. - PubMed

Publication types

MeSH terms

LinkOut - more resources