The Brain Metabolic Patterns of Clozapine- and Fluphenazine-Treated Patients With Schizophrenia During a Continuous Performance Task

Abstract

These changes are consistent with the idea that neuroleptic drugs lead to "compensation" and "adaptation" rather than "normalization" of the functional activities of brain structures in schizophrenia. The overall similarity of their global and regional metabolic effects suggests that both classes of antipsychotic drugs share some common mechanisms of action. One possibility is that of inducing a shift in the balance of cortical to limbic cortex activity. Differential effects in the inferior prefrontal cortex and the basal ganglia might underlie differences in the therapeutic efficacy and side effect profile of clozapine and fluphenazine.

The Brain Metabolic Patterns of Clozapine- and Fluphenazine-Treated Female Patients with Schizophrenia Evidence of a Sex Effect

“…Previous studies (Cohen et al 1988b(Cohen et al , 1997 established that typical neuroleptics, in men, induce a broad decrease in normalized, middle to superior greater than inferior frontal cortex metabolism and an increase in normalized temporal lobe and subcortical metabolism. As was our approach in that work, the female data were first assessed with a multivariate analysis of variance (MANOVA) to reduce the possibility of a type I error.…”

“…All of the female and male schizophrenic patients scanned while receiving fluphenazine or clozapine treatment were part of previous PET studies (Cohen et al 1997(Cohen et al , 1998; with the exception of the female patients and six additional male clozapine-treated patients. Because of the greater number of male patients scanned, the initial analysis and publication of the patient data was in males only, and with only the first 11 clozapinetreated patients.…”

“…Patients were excluded if a significant medical or neurological problem was present. The methods of screening and exclusion criteria for comparison subjects have also been reported (Cohen et al 1997). Size and ages of groups were as follows: clozapine-treated patients, 17 males: 35.4 Ϯ 7.7 years and seven females: 28.2 Ϯ 6.4 years; fluphenazine-treated patients, 22 males: 31.8 Ϯ 6.2 and six females 27.5 Ϯ 5.0; comparison subjects, 41 males: 31.4 Ϯ 8.6 and 40 females: 34.7 Ϯ 11.9.…”

“…Specifically, with respect to positron emission tomography (PET) studies, this absence is at least partially attributable to the relatively small number of subjects scanned in each study. These studies (Cohen et al 1988b(Cohen et al , 1997 established that, as compared to healthy subjects, our male patients treated with typical neuroleptics have a broad decrease in normalized, frontal cortex metabolism with a greater effect on the middle-superior prefrontal region than the inferior prefrontal, and an increase in normalized temporal lobe and subcortical metabolism. The one study of the atypical clozapine, when compared to the typical neuroleptic fluphenazine (Cohen et al 1997) suggested that clozapine engendered a greater reduction in the inferior prefrontal cortex than fluphenazine, but did not seem to increase lateral temporal lobe and had a much smaller effect on normalized metabolic rates in the basal ganglia and thalamus.…”

“…However, the size of the regional metabolic changes we observed with PET in male schizophrenic patients treated with typical neuroleptics, and the reliability of these changes (Cohen et al 1988b(Cohen et al , 1997, encouraged us to compare the metabolic brain patterns of women who were treated with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine to normal controls.…”