Pharmacogenomics and Efficacy of Risperidone Long-term Treatment in Thai Autistic Children and Adolescence

Abstract

Risperidone, atypical antipsychotics, was approved for irritability in autistic disorder. However, some patients had minimal improvement or no response to this treatment. The purpose of this study was to evaluate the association of pharmacogenomics factors and clinical outcomes in autistic children and adolescence who treated with risperidone for long periods. Sixty-seven autistic subjects diagnosed with DSM-IV criteria and treated with risperidone more than 1 year were evaluated clinical symptom by CGI, aggressive, over activity, and repetitive score. Polymorphisms of ABCB1, CYP2D6, DRD2, DRD3, and HTR2A were analyzed. Almost patients showed stable symptom on aggressive (91.04%), over activity (73.13%), repetitive (68.25%) behavior, and all clinical symptoms (82.09%). Only 4.48% of patients showed minimally worse on CGI-I score. Patients in non-stable of all symptom group had DRD2 Taq1A non-wildtype (TT and CT) frequencies higher than clinical stable group (P = 0.046), whereas other genes polymorphism showed no significant association. Interestingly, there was no patient with HTR2A-1438G > A wildtype in all non-stable symptoms. However, there was no significant association due to small sample sizes. Drug levels (RIS, 9OH-RIS, and active moiety) did not show the association with any clinical outcome. Increased appetite was the common ADRs, which associated with high body weight, whereas there was not significantly associated with genetic variations and non-genetic information. In conclusion, risperidone showed efficacy to control autism, especially aggressive symptom in long-term treatment. However, dopamine 2 gene variation affect to non-stable in risperidone treated patients. This study supports pharmacogenomics testing for personalized therapeutics of risperidone in autistic disorder.

Disclosure of interest

The authors have not supplied their declaration of competing interest.