Intramuscular (IM) Olanzapine Versus IM Haloperidol Plus Lorazepam for Acute Agitation in Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder; Agitation
MeSH terms: Psychomotor Agitation; Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of this study was to compare the efficacy and safety of intramuscular 10 mg
      olanzapine versus intramuscular 5 mg haloperidol plus lorazepam 2 mg in the treatment of
      acute agitated schizophrenic patients of Taiwanese populations.
    

Detailed description: 
      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.
    

Intervention name(s): IM olanzapine; IM haloperidol plus lorazepam
Intervention type(s): Drug; Drug
Intervention description(s): 10mg olanzapine IM; IM 5 mg haloperidol plus IM 2 mg lorazepam
Other intervention name(s): zyprexa; haldol and ativan
Intervention MeSH terms: Lorazepam; Haloperidol; Olanzapine; Haloperidol decanoate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; schizoaffective disorder; olanzapine; haloperidol; lorazepam; agitation