Functional effects of antipsychotic drugs: comparing clozapine with haloperidol.
BACKGROUND
Using positron emission tomography (PET) with (15)O water, we compared regional cerebral blood flow (rCBF) patterns induced by clozapine or haloperidol in individuals with schizophrenia. Based on the known clinical characteristics of each drug, we hypothesized that brain regions where the drugs show similar rCBF patterns are among those mediating their antipsychotic actions; whereas, regions where the drugs produce different rCBF patterns are among those mediating their different drug actions, namely, haloperidol's motor side effects or clozapine's unique therapeutic action.


METHODS
Persons with schizophrenia were scanned using PET with (15)O water, first after withdrawal of all psychotropic medication (n = 6), then again after treatment with therapeutic doses of haloperidol (n = 5) or clozapine (n = 5).


RESULTS
Both drugs increased rCBF in the ventral striatum and decreased rCBF in hippocampus and ventrolateral frontal cortex. The rCBF increase associated with haloperidol was greater than that with clozapine in the dorsal and ventral striatum; the rCBF increase with clozapine was greater than that with haloperidol in cortical regions, including anterior cingulate and dorsolateral frontal cortex.


CONCLUSIONS
These data suggest that the rCBF increase in ventral striatum and/or the decrease in hippocampus and/or ventrolateral frontal cortex mediate a common component of antipsychotic action of these drugs. The increased rCBF in dorsal striatum by haloperidol could well be associated with its prominent motor side effects, whereas the increased rCBF in the anterior cingulate or dorsolateral frontal cortex may mediate the superior antipsychotic action of clozapine. The proposals based on these preliminary observations require further study.
Lahti
Adrienne C
AC
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA.
Holcomb
Henry H
HH
Weiler
Martin A
MA
Medoff
Deborah R
DR
Tamminga
Carol A
CA
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010104:Oxygen Radioisotopes; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D010104:Oxygen Radioisotopes; D003024:Clozapine; D006220:Haloperidol