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
. 2015 Dec 21;2015(12):CD003441.
doi: 10.1002/14651858.CD003441.pub3.

'As required' medication regimens for seriously mentally ill people in hospital

Petrina Douglas-Hall  1 , Emma V Whicher
Affiliations

'As required' medication regimens for seriously mentally ill people in hospital

Petrina Douglas-Hall et al. Cochrane Database Syst Rev. .

Abstract

Background: Drugs used to treat psychotic illnesses may take weeks to be effective. In the interim, additional 'as required' doses of medication can be used to calm patients in psychiatric wards. The practice is widespread, with 20% to 50% of people on acute psychiatric wards receiving at least one 'as required' dose of psychotropic medication during their admission.

Objectives: To compare the effects of 'as required' medication regimens with regular patterns of medication for the treatment of psychotic symptoms or behavioural disturbance, thought to be secondary to psychotic illness. These regimens may be given alone or in addition to any regular psychotropic medication for the long-term treatment of schizophrenia or schizophrenia-like illnesses.

Search methods: We searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of MEDLINE, EMBASE, PubMed, CINAHL, BIOSIS, AMED, PsycINFO and registries of clinical trials, in November 2001, March 2006, July 2012 andOctober 2013.

Selection criteria: We aimed to include all relevant randomised controlled trials involving hospital inpatients with schizophrenia or schizophrenia-like illnesses, comparing any regimen of medication administered for the short-term relief of behavioural disturbance, or psychotic symptoms, to be given at the discretion of ward staff ('as required', 'prn') with fixed non-discretionary patterns of drug administration of the same drug(s). This was in addition to regular psychotropic medication for the long-term treatment of schizophrenia or schizophrenia-like illnesses where prescribed.

Data collection and analysis: We independently inspected abstracts and papers for inclusion. If trials had been found, we would have extracted data from the papers and quality assessed the data. For dichotomous data we would have calculated the risk ratios (RR), with the 95% confidence intervals (CI). We would have conducted analyses on an intention-to-treat basis. If data were available we would have completed a 'Summary of findings' table using GRADE.

Main results: We have not been able to identify any randomised trials comparing 'as required' medication regimens to regular regimens of the same drug. Our main outcomes of interest were important changes in (i) mental state, (ii) behaviour, (iii) dose of medication used, (iv) adverse events, (v) satisfaction with care and (iv) cost of care.

Authors' conclusions: There is currently no evidence from within randomised trials to support this common practice. Current practice is based on clinical experience and habit rather than high quality evidence.

PubMed Disclaimer

Conflict of interest statement

Petrina Douglas‐Hall ‐ none known.

Emma Whicher ‐ none known.

Figures

1
1
Prisma flow diagram for search conducted in 2012/13
See this image and copyright information in PMC

Update of

References

References to studies excluded from this review

Baker 2002 {published data only}
    1. Baker R, Kinon B, Liu H, Richey A, Hill A, Bergstrom R, et al. Effectiveness of rapid initial dose escalation of oral olanzapine for acute agitation. Journal of the European College of Neuropsychopharmacology 2002;12(Suppl 3):S256. [Hallo P.2.004]
    1. Baker R, Kinon BJ, Liu H, Richey A, Hill AL, Bergstrom RF, et al. Effectiveness of rapid initial dose escalation of oral olanzapine for acute agitation. International Journal of Neuropsychopharmacology 2002;5(Suppl 1):S127. [P.2.W.044]
    1. Baker RW, Kinon B, Liu H, Schuh L, Bergstrom R, Hill A. Rapid initial dose escalation of oral olanzapine for acute agitation. 12th World Congress of Psychiatry; 2002 Aug 24‐29; Yokohama, Japan. 2002. [MEDLINE: ]
    1. Baker RW, Kinon BJ, Liu H, Richey A, Hill AL, Bergstrom RF, et al. Effectiveness of rapid initial dose escalation of oral olanzapine for acute agitation. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23; Philadelphia, Pennsylvania, USA. 2002. [No. 32]
    1. Baker RW, Kinon BJ, Liu H, Richey A, Hill AL, Bergstrom RF, et al. Effectiveness of rapid initial dose escalation of oral olanzapine for acute agitation. Schizophrenia Research 2003;60:272. - PubMed
Foster 1997 {published data only}
    1. Foster S, Kessel J, Berman ME, Simpson GM. Efficacy of lorazepam and haloperidol for rapid tranquillization in a psychiatric emergency room setting. International Clinical Psychopharmacology 1997;12(3):175‐9. [MEDLINE: ] - PubMed
Hovens 2005 {published data only}
    1. Hovens JE, Dries PJT, Melman CTM, Wapenaar RJC, Loonen AJM. Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open‐label study. Journal of Psychopharmacology 2005;19(1):51‐7. [PsycINFO 2006‐04400‐008] - PubMed
    1. Hovens JEJM, Beijeman S, Tollenaar J, Dries PJT, Loonen AJM. Risperidone versus zuclopentixol in acute psychosis in emergency psychiatry: a prospective naturalistic study. Journal of the European College of Neuropsychopharmacology 2003;13(4):S293. [P.2.035]
Huttunen 1996 {published data only}
    1. Huttunen MO, Tuhkanen H, Haavisto E, Nyholm R, Pitkanen M, Raitasuo V, et al. Low and standard dose depot haloperidol combined with targeted oral neuroleptics. Psychiatric Services 1996;47:83‐5. [MEDLINE: ] - PubMed
Kinon 2001 {published data only}
    1. Kinon B, Rotelli MD, Gilmore JA. Efficacy of olanzapine and adjunctive lorazepam to control agitation in schizophrenia. International Journal of Neuropsychopharmacology 2002;5(Suppl 1):S128. [P.2.W.046]
    1. Kinon BJ, Ahl J, Rotelli MD, McMullen E. Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia. American Journal of Emergency Medicine 2004;22(3):181‐6. [MEDLINE: ] - PubMed
    1. Kinon BJ, Wang L, Rotelli MD, Gilmore JA. The efficacy of olanzapine plus adjunctive lorazepam to control acute agitation in schizophrenia. European Neuropsychopharmacology 2001;11(3):278. [14th Congress of the European College of Neuropsychopharmacology [Congress Information System]: Conifer, Excerpta Medica Medical Communications BV, 2001 P2084#]
Kinon 2008 {published data only}
    1. Kinon BJ, Stauffer VL, Kollack‐Walker S, Chen L, Sniadecki J. Olanzapine versus aripiprazole for the treatment of agitation in acutely ill patients with schizophrenia. Journal of Clinical Psychopharmacology 2008;28(6):601‐7. [MEDLINE: ] - PubMed
    1. Stauffer V, Kinon B, Kollack‐Walker S, Chen L, Sniadecki J. Olanzapine versus aripiprazole for the treatment of agitation in acutely ill patients with schizophrenia. Proceedings of the 161st Annual Meeting of the American Psychiatric Association; 2008 May 3‐8; Washington DC, USA. 2008. - PubMed
Kramer 1978 {published data only}
    1. Kramer M, Roth T, Salis PJ, Zorick FJ. Relative efficacy and safety of loxapine succinate (Loxitane) and thioridazine hydrochloride (Mellaril) in the treatment of acute schizophrenia. Current Therapeutic Research 1978;23(5):619‐31.
Lesem 2001 {published data only}
    1. Lesem MD, Zajecka JM, Swift RH, Reeves KR, Harrigan EP. Intramuscular ziprasidone, 2 mg versus 10 mg, in the short‐term management of agitated psychotic patients. Journal of Clinical Psychiatry 2001;62(1):12‐8. - PubMed
Maoz 2000 {published data only}
    1. Maoz G, Stein D, Meged S, Kurzman L, Levine J, Valevski A, et al. The anti‐aggressive action of combined haloperidol‐propranolol treatment in schizophrenia. European Psychologist 2000;5(4):312‐25.
Neborsky 1984 {published data only}
    1. Neborsky RJ, Janowsky DS, Perel JM, Munson E, Depry D. Plasma‐RBC haloperidol ratios and improvement in acute psychotic symptoms. Journal of Clinical Psychiatry 1984;45(1):10‐3. - PubMed
Potkin 2006 {published data only}
    1. Potkin SG, Gharabawi GM, Greenspan AJ, Mahmoud R, Kosik‐Gonzalez C, Rupnow MF, et al. A double‐blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalisation. Schizophrenia Research 2006;85(1‐3):254‐65. - PubMed
Slotnick 1971 {published data only}
    1. Slotnick VB. Management of the acutely agitated psychiatric patient with parental neuroleptics: the comparative symptom effectiveness profiles of haloperidol and chlorpromazine. 5th World Congress of Psychiatry; 1971 Nov 28 ‐ Dec 4, Ciudad de Mexico, Mexico. Mexico City: La Prensa Medica Mexicana, 1971:531. [Abstract Number; 1085]
Stotsky 1977 {published data only}
    1. Stotsky BA. Relative efficacy of parenteral haloperidol and thiothixene for the emergency treatment of acutely excited and agitated patients. Diseases of the Nervous System 1977;38(12):967‐73. [MEDLINE: ] - PubMed
Zhang 2013 {published data only}
    1. Zhang H, Wang G, Zhao J, Xie S, Xu X, Shi J, et al. Intramuscular ziprasidone versus haloperidol for managing agitation in Chinese patients with schizophrenia. Journal of Clinical Psychopharmacology 2013;33:178‐85. - PubMed

Additional references

Altman 1996
    1. Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996;313:1200. - PMC - PubMed
Asmal 2013
    1. Asmal L, Flegar Srnka J, Wang J, Rummel‐Kluge C, Komossa K, Leucht S. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews 2013, Issue 11. [DOI: 10.1002/14651858.CD006625.pub3] - DOI - PMC - PubMed
Ayd 1985
    1. Ayd FJ, Frank J. Problems with orders for medication as needed. American Journal of Psychiatry 1985;142(8):939‐42. - PubMed
Bagnall 2000
    1. Bagnall A‐M, Kleijnen J, Leitner M, Lewis R. Ziprasidone for schizophrenia and severe mental illness. Cochrane Database of Systematic Reviews 2000, Issue 4. [DOI: 10.1002/14651858.CD001945] - DOI - PubMed
Bland 1997
    1. Bland JM, Kerry SM. 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
Bowden 1999
    1. Bowden MF. Audit: prescription of 'as required' (p.r.n.) medication in an in‐patient setting. Psychiatric Bulletin 1999;23:413‐6.
Chakrabarti 2007a
    1. Chakrabarti A, Bagnall A‐M, Chue P, Fenton M, Palaniswamy V, Wong W, et al. Loxapine for schizophrenia. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD001943.pub2] - DOI - PMC - PubMed
Craig 1995
    1. Craig TJ, Bracken J. An epidemiologic study of prn/stat medication use in a state psychiatric hospital. Annals of Clinical Psychiatry 1995;7(2):57‐64. - PubMed
Craven 1987
    1. Craven JL, Voore PM, Voineskos G. PRN medication for psychiatric inpatients. Canadian Journal of Psychiatry 1987;32(3):199‐203. - PubMed
Deeks 2000
    1. Deeks J. Issues in the selection for meta‐analyses of binary data. Proceedings of the 8th International Cochrane Colloquium; 2000 Oct 25‐28; Cape Town. Cape Town: The Cochrane Collaboration, 2000.
Divine 1992
    1. Divine GW, Brown JT, Frazer LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7:623‐9. - PubMed
Dold 2015
    1. Dold M, Samara MT, Li C, Tardy M, Leucht S. Haloperidol versus first‐generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. Cochrane Database of Systematic Reviews 2015, Issue 1. [DOI: 10.1002/14651858.CD009831.pub2] - DOI - PMC - PubMed
Donner 2002
    1. Donner A, Klar N. Issues in the meta‐analysis of cluster randomized trials. Statistics in Medicine 2002;21:2971‐80. - PubMed
DSM‐5
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th Edition. American Psychiatric Publishing, 2013.
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
Fenton 2007
    1. Fenton M, Rathbone J, Reilly J. Thioridazine for schizophrenia. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD001944.pub2] - DOI - PMC - 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
Gray 1997
    1. Gray R, Smedley N, Thomas B. The administration of PRN medication by mental health nurses. Journal of Psychiatric and Mental Health Nursing 1997;4(1):55‐6. - PubMed
Gulliford 1999
    1. Gulliford MC, Ukoumunne OC, Chinn S. 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
Guy 1976
    1. Guy W. Clinical Global Impression (CGI). Early Clinical Drug eEvaluation (ECDEU) Assessment Manual for Psychopharmacology. Washington DC, USA: National Institute of Mental Health, 1976.
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60. - PMC - PubMed
Higgins 2005
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]. The Cochrane Library. Chichester: John Wiley & Sons, Ltd, 2005, issue 3.
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.
Hor 2010
    1. Hor K, Taylor M. Suicide and schizophrenia: a systematic review of rates and risk factors. Journal of Psychopharmacology 2010;24(4 Suppl):81‐90. - PMC - PubMed
Hutton 2009
    1. Hutton JL. Number needed to treat and number needed to harm are not the best way to report and assess the results of randomised clinical trials. British Journal of Haematology 2009;146(1):27‐30. - PubMed
Juniper 1994
    1. Juniper EF, Guyatt GH, Ferrie PJ, King DR. Sodium cromoglycate eye drops: regular versus "as needed" use in the treatment of seasonal allergic conjunctivitis. Journal of Allergy and Clinical Immunology 1994;94(1):36‐43. - PubMed
Jüni 2001
    1. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001;323:42‐6. - PMC - PubMed
Kay 1986
    1. Kay SR, Opler LA, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Manual. Multi‐Health Systems: North Tonawanda, NY, 1986.
Khanna 2014
    1. Khanna P, Suo T, Komossa K, Ma H, Rummel‐Kluge C, El‐Sayeh HG, et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews 2014, Issue 1. [DOI: 10.1002/14651858.CD006569.pub5] - DOI - PMC - PubMed
Komossa 2010
    1. Komossa K, Rummel‐Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews 2010, Issue 3. [DOI: 10.1002/14651858.CD006654.pub2] - DOI - PMC - PubMed
Komossa 2011
    1. Komossa K, Rummel‐Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, et al. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews 2011, Issue 1. [DOI: 10.1002/14651858.CD006626.pub2] - DOI - PMC - PubMed
Lankappa 2012
    1. Lankappa S, Gandhi R. Quetiapine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2012, Issue 7. [DOI: 10.1002/14651858.CD009935] - DOI
Leonard 1992
    1. Leonard B. Fundamentals of Psychopharmacology. John Wiley & Sons, 1992.
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
Leucht 2008
    1. Leucht C, Kitzmantel M, Kane J, Leucht S, Chua Wan Lian LC. Haloperidol versus chlorpromazine for schizophrenia. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD004278.pub2] - DOI - PMC - PubMed
Marder 2000
    1. Marder S, Kammen D. Biological therapies. In: Sadock BJ, Sadock VA editor(s). Kaplan & Sadock's Comprehensive Textbook of Psychiatry. 7th Edition. Vol. 2, Philadelphia, London: Lippincott Williams & Wilkins, 2000:2376.
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
McGrath 2008
    1. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews 2008;30:67‐76. - PubMed
McLaren 1990
    1. McLaren S, Browne FW, Taylor PJ. A study of psychotropic medication given 'as required' in a regional secure unit. British Journal of Psychiatry 1990;156:732‐5. - PubMed
Meylers 2006
    1. Aronson J. Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. 15th Edition. Vol. 1, Elsevier, 2006.
Milton 1998
    1. Milton J, Lawton J, Smith M, Buckley A. Hidden high‐dose antipsychotic prescribing: effects of p.r.n. doses. Psychiatric Bulletin 1998;22:675‐7.
Newton 1997
    1. Newton KL, Murthy R, Qureshi J. Antipsychotic prescribing in the light of the consensus statement of the College. Psychological Bulletin 1997;21(7):408‐10.
Owens 2000
    1. Cunningham Owens DG, Johnson EC. Treatment and management of schizophrenia. In: López‐Ibor JJ, Gelder MG, Andreasen NC editor(s). New Oxford Textbook of Psychiatry. Oxford: Oxford University Press, 2000:628‐9.
Rattehalli 2010
    1. Rattehalli Ranganath D, Jayaram Mahesh B, Smith M. Risperidone versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD006918.pub2] - DOI - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408‐12. - PubMed
Schulz 2010
    1. Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials 2010;11:32.
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. In: 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).
Stahl 2008
    1. Stahl S. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd Edition. Cambridge University Press, 2008.
Stauffer 2008
    1. Stauffer V, Kinon B, Kollack‐Walker S, Chen L, Sniadecki J. Olanzapine versus aripiprazole for the treatment of agitation in acutely ill patients with schizophrenia. Proceedings of the 161st Annual Meeting of the American Psychiatric Association. Washington DC, USA, 2008 May 3‐8. - PubMed
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.

References to other published versions of this review

Chakrabarti 2007b
    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
Whicher 2002
    1. Whicher E, Morrison M, Douglas‐Hall P. 'As required' medication regimens for seriously mentally ill people in hospital. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD003441] - DOI - PubMed

Publication types

MeSH terms

Substances