Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents.

Abstract

The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcome 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, overactivity and repetitive score) were evaluated. Almost all patients showed stable symptoms on aggressive behaviour (89.02%), overactivity (71.95%), repetitive (70.89%) behaviour 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-wild-type (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 outcome. 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 dopamine 2 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.

• Authors: Nopphadol Nuntamool, Nattawat Ngamsamut, Natchaya Vanwong, Apichaya Puangpetch, Monpat Chamnanphon, Yaowaluck Hongkaew, Penkhae Limsila, Chuthamanee Suthisisang, Bob Wilffert, Chonlaphat Sukasem
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 121 Issue 4 Pg. 316-324 (Oct 2017) ISSN: 1742-7843 [Electronic] England
• PMID: 28470827 (Publication Type: Journal Article)
• Copyright: © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Chemical References

• DRD2 protein, human
• Dopamine Antagonists
• Receptors, Dopamine D2
• Risperidone

Topics

• Adolescent
• Adolescent Behavior (drug effects)
• Age Factors
• Aggression (drug effects)
• Autistic Disorder (diagnosis, drug therapy, genetics, psychology)
• Chi-Square Distribution
• Child
• Child Behavior (drug effects)
• Cross-Sectional Studies
• Diagnostic and Statistical Manual of Mental Disorders
• Dopamine Antagonists (administration & dosage, adverse effects)
• Drug Administration Schedule
• Female
• Gene Frequency
• Haplotypes
• Heterozygote
• Homozygote
• Humans
• Male
• Pharmacogenetics
• Pharmacogenomic Variants
• Prospective Studies
• Receptors, Dopamine D2 (drug effects, genetics, metabolism)
• Risk Factors
• Risperidone (administration & dosage, adverse effects)
• Thailand
• Time Factors
• Treatment Outcome