This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (82)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Schizophrenia  • Randomized Controlled Trial  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

Alan Breier, MD; Karena Meehan, MB, MRCP, MRCPsych; Martin Birkett, BSc; Stacy David, PhD; Iris Ferchland, MSc; Virginia Sutton, PhD; Cindy C. Taylor, PhD; Rebecca Palmer, MS; Martin Dossenbach, MD; Geri Kiesler, RPh; Shlomo Brook, MD; Padraig Wright, MRCPsych, MD

Arch Gen Psychiatry. 2002;59:441-448.

Background  An intramuscular (IM) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia.

Methods  Recently hospitalized acutely agitated patients with schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within 24 hours. A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first injection. Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection.

Results  Olanzapine exhibited a dose-response relationship for reduction in agitation (F_1,179= 14.4; P<.001). Mean PANSS-EC reductions 2 hours after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = -8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P = .01 vs olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection. There were no differences between treatment groups for hypotension, the most frequently reported adverse event, or for clinically relevant changes in the QTc interval. There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol (16.7%) than with 2.5 (P = .03), 5.0 (P = .03), or 7.5 mg (P = .01) of IM olanzapine (0%) or with placebo (0%) (P = .01).

Conclusions  Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile.

From Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind (Drs Breier, David, Sutton, and Taylor, Mr Birkett, and Mss Palmer and Kiesler); Maudsley Hospital, London, England (Dr Meehan); Lilly Research Centre, Eli Lilly and Company Limited, Surrey, England (Dr Wright and Ms Ferchland); Eli Lilly and Company, Vienna, Austria (Dr Dossenbach); Sterkfontein Hospital, Krugersdorp, South Africa (Dr Brook); and the Institute of Psychiatry, University of London, London, England (Drs Wright and Meehan).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Should the PANSS Be Rescaled?
Obermeier et al.
Schizophr Bull 2009;0:sbp124v1-sbp124.
ABSTRACT | FULL TEXT  

A Naturalistic Study of Consecutive Agitated Emergency Department Patients Treated With Intramuscular Olanzapine Prior to Consent
DAMSA et al.
Am. J. Psychiatry 2008;165:535-536.
FULL TEXT  

Methodological Issues in Current Antipsychotic Drug Trials
Leucht et al.
Schizophr Bull 2008;34:275-285.
ABSTRACT | FULL TEXT  

Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine
Raveendran et al.
BMJ 2007;335:865-865.
ABSTRACT | FULL TEXT  

Bradykinesia Induced by Dopamine D2 Receptor Blockade Is Associated with Reduced Motor Cortex Activity in the Rat
Parr-Brownlie and Hyland
J. Neurosci. 2005;25:5700-5709.
ABSTRACT | FULL TEXT  

Intramuscular Olanzapine in the Management of Acute Agitation
Tulloch and Zed
The Annals of Pharmacotherapy 2004;38:2128-2135.
ABSTRACT | FULL TEXT  

10 mg intramuscular olanzapine reduces acute agitation in schizophrenia more effectively than lower doses
Smith
Evid. Based Ment. Health 2003;6:27-27.
FULL TEXT  

Recent Developments in Pharmacotherapy for the Acutely Psychotic Patient
Daniel
J Am Psychiatr Nurses Assoc 2002;8:S40-S47.