FDG-PET and MRI imaging of the effects of sertindole and haloperidol in the prefrontal lobe in schizophrenia.
Sertindole, a 2nd generation antipsychotic with low movement disorder side effects, was compared with haloperidol in a 6-week crossover study. Fifteen patients with schizophrenia (mean age=42.6, range=22-59, 11 men and 4 women) received sertindole (12-24 mg) or haloperidol (4-16 mg) for 6 weeks and then received a FDG-PET scan and an anatomical MRI. Patients were then crossed to the other treatment and received a second set of scans at week 12. Dose was adjusted by a physician blind to the medication type. Brodmann areas were identified stereotaxically using individual MRI templates applied to the coregistered FDG-PET image. Sertindole administration was associated with higher dorsolateral prefrontal cortex metabolic rates than haloperidol and lower orbitofrontal metabolic rates than haloperidol. This effect was greatest for gray matter of the dorsolateral Brodmann areas 8, 9, 10, 44, 45, and 46. Patients were further contrasted with an approximately age and sex-matched group of 33 unmedicated patients with schizophrenia and with a group of 55 normal volunteers. Sertindole administration was associated with greater change toward normal values and away from the values found in the unmedicated comparison group for dorsolateral prefrontal cortex gray matter and white matter underlying medial prefrontal and cingulate cortex. These results are consistent with the low motor side-effect profile of sertindole, greater improvement on prefrontal cognitive tasks with sertindole than haloperidol, and with the tendency of 2nd generation antipsychotic drugs to have greater frontal activation than haloperidol.
Buchsbaum
Monte S
MS
University of California, San Diego, Department of Psychiatry, USA. monte.buchsbaum@gmail.com
Haznedar
Mehmet
M
Newmark
Randall E
RE
Chu
King-Wai
KW
Dusi
Nicola
N
Entis
Jonathan J
JJ
Goldstein
Kim E
KE
Goodman
Chelain R
CR
Gupta
Adarsh
A
Hazlett
Erin
E
Iannuzzi
James
J
Torosjan
Yuliya
Y
Zhang
Jane
J
Wolkin
Adam
A
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001931:Brain Mapping; D005260:Female; D019788:Fluorodeoxyglucose F18; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D055815:Young Adult
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D019788:Fluorodeoxyglucose F18; C066304:sertindole; D006220:Haloperidol