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Titolo:
INDIVIDUAL VARIATION IN D-2 DOPAMINE-RECEPTOR OCCUPANCY IN CLOZAPINE-TREATED PATIENTS
Autore:
PICKAR D; SU TP; WEINBERGER DR; COPPOLA R; MALHOTRA AK; KNABLE MB; LEE KS; GOREY J; BARTKO JJ; BREIER A; HSIAO J;
Indirizzi:
NIMH,EXPT THERAPEUT BRANCH,BLDG 10,RM 4N212 BETHESDA MD 20892 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH WASHINGTON DC 20032
Titolo Testata:
The American journal of psychiatry
fascicolo: 12, volume: 153, anno: 1996,
pagine: 1571 - 1578
SICI:
0002-953X(1996)153:12<1571:IVIDDO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; FREE SCHIZOPHRENIC-PATIENTS; PLASMA HOMOVANILLIC-ACID; I-123 IBZM; CLINICAL-RESPONSE; ATYPICAL NEUROLEPTICS; ANTIPSYCHOTIC-DRUGS; IMAGING AGENT; BASAL GANGLIA; HUMAN-BRAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
D. Pickar et al., "INDIVIDUAL VARIATION IN D-2 DOPAMINE-RECEPTOR OCCUPANCY IN CLOZAPINE-TREATED PATIENTS", The American journal of psychiatry, 153(12), 1996, pp. 1571-1578

Abstract

Objective: The objectives of this study were 1) to pursue the question of clozapine's striatal D-2 occupancy in relation to its clinical effectiveness; 2) to investigate the relation between schizophrenic symptoms, clozapine blood levels, and estimated D-2 occupancy during clinically stable and unstable conditions; and 3) to eh amine long-term stability in D-2 occupancy. Method: Specific binding of the D-2 radioligand [I-123]benzamide [I-123]IBZM) was studied with single photon emission computed tomography in 13 patients with schizophrenia when they were clinically stable during chronic clozapine treatment, after clozapine dose reduction of greater than or equal to 50%, and in a subgroup (N=7) after restabilization on clozapine regimens. Clozapine's estimatedD-2 occupancy was based on comparison with values from drug-free normal subjects. Results: A wide range of estimated D-2 occupancies (18% to greater than or equal to 80%) were associated with sustained, favorable response to clozapine without correlation with residual symptoms. Clonzapine blood levels were negatively related to [(123)]IBZM specific binding. Acute dose reduction was associated with predicted worsening in positive and negative symptoms and increases in [I-123]IBZM specific binding. Independent of clozapine blood level, patients with more symptoms showed lower [I-123]IBZM specific binding, consistent with competition of endogenous dopamine for D-2 binding sites in patients with greater symptoms. Restabilization on clozapine regimens produced D-2Occupancies closely correlated with baseline values. Conclusions: There was no evidence for a critical degree of D-2 occupancy required to sustain clozapine's therapeutic effects across subjects. Simple linearregression was the best-fit model for clozapine's D-2 occupancy. Longitudinal follow-up suggests stability over time of D-2 occupancy in relation to dose and clinical response within individual patients.

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Documento generato il 10/07/20 alle ore 15:53:31