Cytochrome P450 enzyme especially CYP2D6 plays a major role in biotransformation. The interindividual variations of treatment response and toxicity are influenced by the polymorphisms of this enzyme. This review emphasizes the effect of CYP2D6 polymorphisms in risperidone treatment in terms of basic knowledge, pharmacogenetics, effectiveness, adverse events, and clinical practice. Although the previous studies showed different results, the effective responses in risperidone treatment depend on the CYP2D6 polymorphisms. Several studies suggested that CYP2D6 polymorphisms were associated with plasma concentration of risperidone, 9-hydroxyrisperidone, and active moiety but did not impact on clinical outcomes. In addition, CYP2D6 poor metabolizer showed more serious adverse events such as weight gain and prolactin than other predicted phenotype groups. The knowledge of pharmacogenomics of CYP2D6 in risperidone treatment is increasing, and it can be used for the development of personalized medication in term of genetic-based dose recommendation. Moreover, the effects of many factors in risperidone treatment are still being investigated. Both the CYP2D6 genotyping and therapeutic drug monitoring are the important steps to complement the genetic-based risperidone treatment.

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 (χ = 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.

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