Clozapine may partially compensate for task-related brain perfusion abnormalities in risperidone-resistant schizophrenia patients.
BACKGROUND
Previous reports show different cerebral activity patterns during treatment with clozapine and typical neuroleptics. However, to date no study has directly compared the brain activity patterns while subjects are undergoing treatment with clozapine and other atypical antipsychotics. This comparison is of interest, given the probably different mechanism of action of clozapine in comparison with other atypicals.


OBJECTIVE
To assess the effect of clozapine on perfusion deviations still evident during treatment with risperidone.


METHODS
Here we used hexamethylene-propylenaminoxime single photon emission computed tomography to compare the perfusion patterns observed during the performance of a Stroop test in 10 patients sequentially treated with risperidone and clozapine, owing to a lack of response to the former, and in 10 healthy controls.


RESULTS
Patients on risperidone showed decreased perfusion as compared to controls in the medial prefrontal, middle cingulate and insular regions, as well as increased activities in brain stem and the posterior hippocampus. After receiving clozapine, the same patients showed an even wider prefrontal perfusion deficit and the brain stem was still hyperactive, but the abnormalities in the cingulate cortex, insula and hippocampus had disappeared. Clinical improvement was directly related to an increase in thalamic perfusion.


CONCLUSIONS
Clozapine may alleviate hyperactivity in the limbic system in schizophrenia and may facilitate activation of the regions involved in cognitive tasks to a greater degree than risperidone, as well as eliciting greater inhibition of the PF region.
Molina
V
V
Department of Psychiatry, Hospital Clínico Universitario, Salamanca, Spain. vmolina@usal.es
Tamayo
P
P
Montes
C
C
De Luxán
A
A
Martin
C
C
Rivas
N
N
Sancho
C
C
Domínguez-Gil
A
A
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D003024:Clozapine / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon; D017211:Treatment Failure
D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone