Patients with schizophrenia who were treated with an atypical antipsychotic after their first psychotic episode had less change in brain volume than patients treated with a conventional antipsychotic, according to an article in the April issue of the Archives of General Psychiatry.

Structural brain abnormalities such as reductions in gray matter volume have been consistently described in patients with schizophrenia, according to background information in the article. The current study was designed to test whether patients treated with olanzapine would have less reduction in gray matter volume than patients treated with haloperidol and whether changes in volume were associated with changes in disturbed thinking and general mental function.

Jeffrey A. Lieberman, MD, and his American colleagues studied 161 patients who were randomized to haloperidol or olanzapine at the time of a first psychotic episode (baseline). Patients underwent neurocognitive testing and magnetic resonance imaging at baseline, and then at 12, 24, 52, and 104 weeks of treatment; the five-year longitudinal study involved 14 academic medical centers. A matched sample of 58 healthy volunteers underwent MRI and was used for comparison on brain volume measures.

"The principle new finding of this study is the significant difference in the course and magnitude of these changes between patients treated with haloperidol, a conventional antipsychotic, and olanzapine, an atypical antipsychotic," the authors reported.

"Specifically, olanzapine was associated with less such change in brain volume during and in the aftermath of the first psychotic episode. These differences in volume change were highlighted by the comparison with healthy volunteers, who showed no significant reductions in gray matter volume and a trajectory similar to that of the olanzapine group."

"The associations between greater decrease in whole brain gray matter and less improvement in neurocognitive functioning, and greater improvements on PANSS total and negative subscales with less increase in lateral ventricular volume indicate that treatment effects on brain volume and the behavioral pathology of the illness may be associated," the authors wrote.

"Although these results must be confirmed, they suggest that a significant difference exists between a typical antipsychotic (haloperidol) and an atypical agent (olanzapine) that is due to either a safety or efficacy advantage and reflected by a differential pattern of brain volume change and clinical response," the authors concluded. "Future clinical studies should attempt to verify whether the early stage of psychosis is associated with brain volume changes and whether antipsychotics can neurobiologically alter the course of the disease."