THE BRAIN METABOLIC PATTERNS OF CLOZAPINE-TREATED AND FLUPHENAZINE-TREATED PATIENTS WITH SCHIZOPHRENIA DURING A CONTINUOUS PERFORMANCE TASK

Background: The comparison of the effects of 2 classes of neuroleptic drugs on regional brain functional activities may reveal common mechan isms of antipsychotic drug efficacy. Methods: The regional cerebral gl ucose metabolic rates of patients with schizophrenia who were and were not receiving neuroleptic drugs and normal control subjects were obta ined by positron emission tomography using fludeoxyglucose F 18 as the tracer. Results: Compared with normal controls and patients not recei ving medication, fluphenazine hydrochloride- and clozapine-treated pat ients had lower global gray matter absolute metabolic rates throughout the cortex. When normalized regional glucose metabolic rates were exa mined, both medications lowered rates in the superior prefrontal corte x and increased rates in the limbic cortex. Fluphenazine, but not cloz apine, increased metabolic rates in the subcortical and lateral tempor al lobes, whereas clozapine, but not fluphenazine, decreased inferior prefrontal cortex activity. Conclusions: These changes are consistent with the idea that neuroleptic drugs lead to ''compensation'' and ''ad aptation'' 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 an tipsychotic drugs share some common mechanisms of action. One possibil ity is that of inducing a shift in the balance oi cortical to limbic c ortex activity. Differential effects in the inferior prefrontal cortex and the basal ganglia might underlie differences in the therapeutic e fficacy and side effect profile of clozapine and fluphenazine.