Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial.

Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.