Olanzapine vs. Low-dose Olanzapine Plus Trifluoperazine

Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Surveys have shown that antipsychotic polypharmacy are frequently prescribed, yet few randomized, double-blind clinical trials have examined this practice. Olanzapine, an atypical antipsychotic agent, has low incidence of extrapyramidal symptom but with high cost compared to trifluoperazine. It has been reported that mean doses of typical antipsychotics less than 600 mg per day of chlorpromazine or its equivalent has no higher risk of extrapyramidal symptom than atypical antipsychotics. The objective of the study is to compare the efficacy and safety of the olanzapine (10 mg per day) and olanzapine (5 mg per day) plus trifluoperazine (5 mg per day) in the treatment of acute psychotic exacerbations of schizophrenia. In this 6-week, double-blind, fixed-dose study, patients with schizophrenia are randomly assigned to olanzapine (10 mg per day)) or olanzapine (5 mg per day) plus trifluoperazine (5 mg per day). The hypothesis is that the two treatment groups have the similar efficacy and safety, but different cost. The primary efficacy measure is change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes include Clinical Global Impression-Severity (CGI-S), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF), Short Form-36 (SF-36), Mini Mental State Examination (MMSE). Safety assessments include the change from baseline on Simpson-Angus Rating Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BAS), and UKU Side-effects Rating Scale, and the change from baseline in prolactin levels, body weight, vital sign, blood pressure, Bazett's correction of QT interval (QTc interval), fasting glucose level, and lipid panel (cholesterol, high density lipid protein, low density lipid protein, and triglyceride).