Aperçu: G.M.
L'objectif
de cette étude était d'évaluer l'association des facteurs
pharmacogénomiques et des résultats cliniques chez les enfants et les
adolescents autistes qui ont été traités avec de la risperidone pendant
de longues périodes. Quatre-vingt-deux
sujets autistes diagnostiqués avec DSM-IV et qui ont été traités avec
de la risperidone pendant plus d'un an ont été recrutés.
La pharmacogénomique et les résultats cliniques (CGI-I, agressif, suractivité et score répétitif) ont été évalués.
Presque
tous les patients présentaient des symptômes stables sur le
comportement agressif (89,02%), la suractivité (71,95%), le comportement
répétitif (70,89%) et tous les symptômes cliniques (81,71%).
L'augmentation
de l'appétit était la réaction indésirable la plus fréquente et
associée à un poids corporel plus élevé, alors qu'elle n'était pas
significativement associée aux variations génétiques et à l'information
non génétique. En
conclusion, la rispéridone a montré une efficacité pour lutter contre
l'autisme, en particulier les symptômes agressifs dans le traitement à
long terme. Cependant,
Taq1A T-carrier du gène du récepteur dopamine2 est associée à une
réponse non stable chez les patients traités par risperidone.
Basic Clin Pharmacol Toxicol. 2017 May 4. doi: 10.1111/bcpt.12803.
Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents
Nuntamool N1,2,3, Ngamsamut N4, Vanwong N1,2, Puangpetch A1,2, Chamnanphon M1,2, Hongkaew Y1,2, Limsila P4, Suthisisang C5, Wilffert B6,7, Sukasem C1,2.
Author information
- 1
- Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
- 2
- Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
- 3
- Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand.
- 4
- Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Department of Mental Health Services, Ministry of Public Health, Samut Prakarn, Thailand.
- 5
- Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
- 6
- University of Groningen, Unit of PharmacoTherapy, -Epidemiology & -Economics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
- 7
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
The
purpose of this study was to evaluate the association of
pharmacogenomic factors and clinical outcomes in autistic children and
adolescents who were treated with risperidone for long periods.
Eighty-two autistic subjects diagnosed with DSM-IV and who were treated
with risperidone for more than 1 year were recruited. Pharmacogenomics
and clinical outcome (CGI-I, aggressive, over-activity and repetitive
score) were evaluated. Almost all patients showed stable symptoms on
aggressive behaviour (89.02%), over-activity (71.95%), repetitive
(70.89%) behavior and all clinical symptoms (81.71%). Only 4.48% of
patients showed minimally worse CGI-I score. Patients in the non-stable
symptom group had DRD2 Taq1A non-wildtype (TT and CT) frequencies higher
than the clinically stable group (P = 0.04), whereas other gene
polymorphisms showed no significant association. Haplotype ACCTCAT
(rs6311, rs1045642, rs1128503, rs1800497, rs4436578, rs1799978, rs6280)
showed a significant association with non-stable clinical outcome (χ2
= 6.642, p = 0.010). Risperidone levels showed no association with any
clinical outcomes. On the other hand, risperidone dose, 9-OH Risperidone
levels and prolactin levels were significantly higher in the non-stable
compared to the stable symptom group (P = 0.013, P = 0.044, P = 0.030).
Increased appetite was the most common adverse drug reaction and
associated with higher body weight, whereas it was not significantly
associated with genetic variations and non-genetic information. In
conclusion, risperidone showed efficacy to control autism, especially
aggressive symptoms in long-term treatment. However, Taq1A T - carrier
of dopamine2 receptor gene is associated with non-stable response in
risperidone-treated patients. This study supports pharmacogenomics
testing for personalized therapy with risperidone in autistic children
and adolescents. This article is protected by copyright. All rights
reserved.
This article is protected by copyright. All rights reserved.
- PMID: 28470827
- DOI: 10.1111/bcpt.12803
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