|Reference code: ||PT/FB/BL-2006-036.17|
|Location: ||Arquivo PCA - Pasta 18/2006|
|The effects of single dose aripiprazole and haloperidol on resting blood flow in healthy volunteers|
|Publication year: ||2009|
The direct effects of typical and atypical antipsychotics on blood flow remain unclear. PET, SPECT and cerebrography have been used to indirectly explore the effects of antipsychotic drugs on blood flow by studying metabolism. These studies suggest that typical and atypical antipsychotics may have differential effects in the striatal and frontal cortices but more similar effects on temporal cortex metabolism. Unfortunately, most studies have evaluated individuals with psychosis in which the pathology of the disorder and previous antipsychotic treatment history play a role in the findings. Furthermore, most studies have not directly compared the effects of typical and atypical antipsychotics. In this study we directly compare the differential effects of typical and atypical antipsychotics on resting blood flow in healthy individuals. Studying healthy individuals, in whom perfusion alterations are not confounded by pathophysiological factors, allows us to better estimate the direct effects of these drugs on brain physiology.
Single doses of haloperidol (3 mg) and aripiprazole (10 mg) were administered to 17 healthy Caucasian, right handed males (mean age 23yrs, SD3) in a repeated measures, randomised, double-blind, placebo controlled design. Volunteers had no current or past psychiatric history themselves or in their first degree relatives. Volunteers abstained from substance use and smoking for at least 3 months prior to the study. Four hours post treatment, a continuous arterial spin labeling sequence was used to obtain a direct measure of blood flow using a 1.5 Tesla scanner. Sixty-four volumes were acquired with a slice thickness of 3.3 mm (including inter-slice gap) over 6 minutes. A perfusion-weighted image was produced via the subtraction of the image in which blood had been labeled from that in which it had not and co-registered with a high resolution structural image. Between-subject analysis was performed on global perfusion using a random effects model at the second level.
Compared with placebo, haloperidol significantly increased perfusion in the putamen bilaterally, in the right parahippocampal gyrus and in the medial frontal cortex bilaterally (p < 0.001, corrected; effect size=0.8). Compared with placebo, aripiprazole increased perfusion in the left putamen only (p < 0.001, corrected; effect size=0.6).
Similar to the findings for metabolism in patients, striatal blood flow increased with both typical and atypical antipsychotics. This change was more widespread following haloperidol. Unexpectedly, haloperidol was also associated with increased blood flow in the frontal and temporal regions, whereas no such changes were found following aripiprazole.
This study provides the first evidence that regional, antipsychotic-specific alterations in rCBF occur within 4 hours of administration of a single antipsychotic dose in healthy volunteers. Furthermore, these alterations in perfusion are independent from pathophysiological processes, and provide important insight into basal brain function in populations receiving different antipsychotic medications.
The findings have important implications for the interpretation of functional and structural imaging findings in schizophrenia and for understanding the different side effect profiles for these drugs.
|Accessibility: ||Document does not exist in file|
|Secondary author(s): |
|Zelaya, F., Reinders, S., Marques, T. R., Kapur, S., Murray, R., McGuire, P., Williams, S., Pariante, C., Dazzan, P.|
|Document type: |
|Number of reproductions: |
|Handley, R., Zelaya, F., Reinders, S., Marques, T. R., Kapur, S., Murray, R., McGuire, P., Williams, S., Pariante, C., & Dazzan, P. (2009). The effects of single dose aripiprazole and haloperidol on resting blood flow in healthy volunteers. European Neuropsychopharmacology, 19(Suppl. 3), S560-S561.|
|Indexed document: ||Yes|
|Keywords: ||Neuroimaging / Neuroleptics / Antipsychotics / Schizophrenia / Functional magnetic resonance imaging (fMRI)|