A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.
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.
Breier
Alan
A
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, DC 1748, Indianapolis, IN 46285, USA. Breier_Alan@lilly.com
Meehan
Karena
K
Birkett
Martin
M
David
Stacy
S
Ferchland
Iris
I
Sutton
Virginia
V
Taylor
Cindy C
CC
Palmer
Rebecca
R
Dossenbach
Martin
M
Kiesler
Geri
G
Brook
Shlomo
S
Wright
Padraig
P
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001569:Benzodiazepines; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000188:drug therapy*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine