CYP2D6 polymorphisms and their influence on risperidone treatment

Abstract

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.

Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment

“…The CYP2D6 gene is highly polymorphic, resulting in large individual differences in CYP2D6 enzymatic activity 59 , 60 . Similarly, genetic variants in CYP3A , CYP1A2, and the ABCB1 membrane transporter, P-glycoprotein, have also been suggested to regulate the bioavailability of antipsychotic drugs 61 . Moreover, a recent study highlighted an interaction between pharmacogenetic factors and antipsychotic influences on potassium channel activity as another potential source of individual variation in response 62 .…”

Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children

“…In contrast, CYP2D6 ultra-rapid metabolizers, who have duplicate or multiple functional copies of the CYP2D6 gene, may be at risk for therapeutic failure. There are few studies in adults supporting CYP–risperidone interaction with respect to pharmacokinetics, efficacy, and side effects [ 104 , 105 , 106 , 107 , 108 , 109 ], whereas others have failed to find risperidone–CYP associations [ 110 ]. Some studies have also demonstrated the clinical impact of CYP2D6 genotype in children.…”

Evaluation of CYP2D6 phenotype in the Yoruba Nigerian population

“…Gaedigk et al[58], and Zineh et al[59], have proposed an Activity Score (AS) that are calculated from the CYP2D6 gene and use to determine the CYP2D6 metabolic activities of an individual. Vanwong et al using risperidone as a probe [60], Puangpetch et al [61], in Thailand, and Dodgen et al in South Africa [31], reported a good correlation between AS, CYP2D6 genotypes and measured phenotypes.…”