The Effects of Olanzapine on the 5 Dimensions of Schizophrenia Derived by Factor Analysis: Combined Results of the North American and International Trials

Background: The choice of drug to treat a patient with schizophrenia is one of the most critical clinical decisions. Controversy exists on the differential efficacy of olanzapine.

Data Sources and Study Selection: Raw data from all 4 registrational double-blind, random-assignment studies of olanzapine compared with placebo or haloperidol were obtained from Eli Lilly and Company for this meta-analysis.

Method: Analysis of covariance of the intent-to-treat last-observation-carried-forward endpoint scores was used to assess efficacy on Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) total scores and the 5 factors derived by factor analysis (negative symptoms, positive symptoms, disorganized thoughts, impulsivity/hostility, and anxiety/depression).

Results: Olanzapine produced a statistically significantly greater reduction in schizophrenic symptoms than haloperidol (p < .05) on total scores on the BPRS and PANSS on each of the 5 factors as well as on almost all items. Olanzapine induced a response at a rate equal to that induced by haloperidol in the first few weeks, but by the end of the study produced a greater percentage of responders. Compared with haloperidol, olanzapine produced a somewhat greater response on symptoms responsive to haloperidol, but a markedly better response on symptoms unresponsive to haloperidol. This difference favoring olanzapine occurred to an equal degree in all subgroups examined. The incidence of parkinsonism or akathisia following olanzapine treatment was extremely low and not statistically distinguishable from placebo.

Conclusion: Olanzapine produced a greater improvement than haloperidol particularly by benefiting a much larger number of items or factors. Extrapyramidal side effects and akathisia during olanzapine treatment were statistically indistinguishable from effects seen with placebo.