To date, there have been no published reports of clinical studies of IM olanzapine versus IM
haloperidol plus lorazepam in acute schizophrenia patients with moderate to severe degree of
agitation. The latter combination of treatment is used quite often as a traditional way to
treat agitated schizophrenia patients.
Study Design:
This is a randomized, active-controlled, parallel-group study, consisting of screening and
treatment phase. Patients completing the screening phase would be randomized to receive
either 10mg olanzapine IM or 5 mg haloperidol plus 2 mg lorazepam IM . The ratio of
randomization was 1:1. Treatment assignments are based on a computer-generated randomization
code supplied by central unit with block designs. Patients can receive a maximum of 3
injections within the first 24-hour period. Second and third injections are used under the
clinical judgment of investigators. The second injection is allowed after 2-hour has elapsed
since first injection. The third injection is allowed after 4-hour have passed since the
second injection. Prohibited medications include antiarrythmics, antipsychotics,
antidepressants, anticonvulsants, antiemetics, and other psychotropic drugs.
Efficacy Assessments:
Patients are assessed by the study investigators at the screening visit and at 15, 30, 60,
120 minutes after first injection. The primary efficacy measure is PANSS-EC, which includes
the items tension, uncooperativeness, hostility, poor impulse control, excitement and is
derived from the PANSS by its originators using a principal-components factor analysis.
Agitation is further assessed by the Agitation-Calmness Evaluation Scale (ACES) (Copyright
1998, Eli Lilly and Company; all rights reserved). Clinical Global
Impression-Severity（CGI-S）scale37 is used to assess general psychiatric condition. For each
patient, the same rater conducted the assessment throughout the study.
Safety assessments:
During the 24-hour treatment period, safety is assessed by clinical examination and
laboratory investigations, recording spontaneously reported adverse events, completing the
Simpson-Angus Scale (SAS) and Barnes Akathisia Scales (BAS).
Statistical Procedures:
The efficacy analyses were based on intent to treat (ITT) population defined as consisting of
all randomized subjects. The last observation carried forward (LOCF) dataset was used to
estimate the missing data. Data were analysed using statistical program R Language version
2.8.0 (http://www.r-project.org/), with significance set at p < .05. Demographic
characteristics and clinical parameters at baseline were compared by treatment group using
the t-test for continuous variables and chi-square test for categorical variables. The
primary treatment comparison was 2-hour PANSS-EC scores after first injection. Continuous
efficacy and safety data were evaluated by multiple linear regression, adjusting for
treatment group, center, and treatment-by-center interaction. The treatment-by-center
interaction was tested at the 0.10 significant levels and dropped from the model if it was
not statistically significant. To compare the number difference in adverse events between two
treatment groups, Fisher's exact test was used due to low cell counts.