期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 26, 期 5, 页码 975-988出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0278-5846(02)00218-X
关键词
clinical correlations; dihydroxyphenylethyleneglycol; homovanillic acid; 5-hydroxyindoleacetic acid; plasma; 9-hydroxyrisperidone; red blood cell; risperidone; schizophrenia; tryptophan; whole blood serotonin
The aim of the study was to establish a relationship between the clinical efficacy of risperidone (Risp), the biological levels of Risp and its metabolite, 9-hydroxyrisperidone (9-OH-Risp), and the turnover of blood biogenic amines during a long-term treatment (1 year). Risp is one of the newer atypical antipsychotic drugs with potent serotonin (5HT(2)), moderate D-2 and real alpha(1)-alpha(2) adrenoreceptor antagonistic effects. The study has been performed in an open setting and included 17 patients, but only 15 were followed-up from 3 to 12 months. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI), the Global Assessment of Functioning Scale (GAF), the Quality of Life Scale (QLS) and the Extrapyramidal Symptoms Rating Scale (ESRS) and the determinations of plasma and red blood cell (RBC) Risp and 9-OH-Risp, whole blood 5HT and tryptophan (Trp), plasma homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5HIAA) and dihydroxyphenylethyleneglycol (DHPG). The therapeutic drug monitoring needed oral Risp daily dose of 4.5 +/- 2.3 mg (range 2-8) and the stabilized concentrations (ng/ml) at endpoint in plasma and RBC were 10 +/- 8 (range 1-23) and 3.5 +/- 2 (range 1-8) for Risp and 29 +/- 19 (range 8-70) and 11.5 +/- 6.6 (range 2.6-22.5) for 9-OH-Risp, respectively. 9-OH-Risp appears to be the major active metabolite compound at higher concentrations than Risp. Positive linear correlations were found only between plasma and RBC 9-OH-Risp and the daily dose and the score of the GAF. Statistically significant clinical results showed that Risp is a potent antipsychotic agent efficacious both on positive and negative symptoms and on quality of life. Positive symptoms decreased after about the second month and the negative symptoms improved secondly. Patients (n=8) who responded to Risp were characterized, on the long-term, by a statistically significant decrease of whole blood 5HT and increase of plasma DHPG. (C) 2002 Elsevier Science Inc. All rights reserved.
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