PMID- 12369274
OWN - NLM
STAT- MEDLINE
DCOM- 20030211
LR  - 20190910
IS  - 0278-5846 (Print)
IS  - 0278-5846 (Linking)
VI  - 26
IP  - 5
DP  - 2002 Jun
TI  - Long-term pharmacoclinical follow-up in schizophrenic patients treated with 
      risperidone. Plasma and red blood cell concentrations of risperidone and its 
      9-hydroxymetabolite and their relationship to whole blood serotonin and 
      tryptophan, plasma homovanillic acid, 5-hydroxyindoleacetic acid, 
      dihydroxyphenylethyleneglycol and clinical evaluations.
PG  - 975-88
AB  - 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 (5HT2), moderate D2 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.
FAU - Aymard, Nicole
AU  - Aymard N
AD  - Unite de Pharmacologie, Laboratoire Central, Centre Hospitalier Sainte-Anne, 
      Paris, France.
FAU - Viala, Annie
AU  - Viala A
FAU - Clement, Marie-Noelle
AU  - Clement MN
FAU - Jacquot, Marc
AU  - Jacquot M
FAU - Vacheron, Marie-Noelle
AU  - Vacheron MN
FAU - Gauillard, Jacques
AU  - Gauillard J
FAU - Caroli, Francois
AU  - Caroli F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Biomarkers)
RN  - 333DO1RDJY (Serotonin)
RN  - 534-82-7 (Methoxyhydroxyphenylglycol)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - 8DUH1N11BX (Tryptophan)
RN  - L6UH7ZF8HC (Risperidone)
RN  - UEH9K539KJ (3,4-dihydroxyphenylglycol)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Biomarkers/blood
MH  - Female
MH  - Follow-Up Studies
MH  - Homovanillic Acid/*blood
MH  - Humans
MH  - Hydroxyindoleacetic Acid/*blood
MH  - Male
MH  - Methoxyhydroxyphenylglycol/*analogs & derivatives/*blood
MH  - Middle Aged
MH  - Risperidone/*blood/metabolism/therapeutic use
MH  - Schizophrenia/blood/*drug therapy
MH  - Serotonin/*blood
MH  - Tryptophan/*blood
EDAT- 2002/10/09 04:00
MHDA- 2003/02/13 04:00
CRDT- 2002/10/09 04:00
PHST- 2002/10/09 04:00 [pubmed]
PHST- 2003/02/13 04:00 [medline]
PHST- 2002/10/09 04:00 [entrez]
AID - S0278-5846(02)00218-X [pii]
AID - 10.1016/s0278-5846(02)00218-x [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2002 Jun;26(5):975-88. doi: 
      10.1016/s0278-5846(02)00218-x.