Abstract
The second generation antipsychotic drug risperidone is widely used in the field of child and adolescent psychiatry to treat conditions associated with disruptive behavior, aggression and irritability, such as autism spectrum disorders. While risperidone can provide symptomatic relief for many patients, there is considerable individual variability in the therapeutic response and side-effect profile of the medication. One well established biological factor that contributes to these individual differences is genetic variation in the cytochrome P450 enzyme 2D6. The 2D6 enzyme metabolizes risperidone and therefore affects drug levels and dosing. In the present review, we summarize the current literature on 2D6 variants and their effects on risperidone responses, specifically in children and adolescents. Relevant articles were identified through systematic review, and after irrelevant articles were discarded, ten studies were included in the review. Most prospective studies were well controlled, but often did not have a large enough sample size to make robust statements about rarer variants, including those categorized as ultra-rapid and poor metabolizers. Individual studies demonstrated a role for different genetic variants in risperidone drug efficacy, pharmacokinetics, hyperprolactinemia, weight gain, extrapyramidal symptoms and drug–drug interactions. Where studies overlapped in measurements, there was typically a consensus between results. These findings indicate that the value of 2D6 genotyping in the youth population treated with risperidone requires further study, in particular with the less common variants.
Highlights
Risperidone is a second generation (“atypical”) antipsychotic drug used for the treatment of multiple psychiatric disorders, including schizophrenia, bipolar disorder and symptoms associated with autism spectrum disorder (ASD) (FDA Label 2009)
The present review considers the importance of pharmacogenomic factors, with a specific focus on one confounding factor that significantly affects risperidone treatment outcome: CYP2D6 metabolic phenotype
An OVID (July 2017) electronic search of the MEDLINE and EMBASE databases was performed to find studies that examined the effects of CYP2D6 metabolic phenotypes on risperidone treatment outcomes in children and adolescents, using the following search strategy: “Cytochrome P450 Enzyme System” or “CYP2D6” and “Antidepressive Agents” or “Antipsychotic Agents” or “antidepress*” or “antipsychotic*”
Summary
Risperidone is a second generation (“atypical”) antipsychotic drug used for the treatment of multiple psychiatric disorders, including schizophrenia, bipolar disorder and symptoms associated with autism spectrum disorder (ASD) (FDA Label 2009). Risperidone was the second most commonly used antipsychotic drug in the United States by 2006 and continues to be widely used in various psychiatric disorders prevalent in pediatric populations, including bipolar disorder, schizophrenia, attention deficit hyperactivity disorder, and ASD (e.g., symptoms of irritability) [1–5]. Variation in drug treatment outcomes between youth and adults is a well-characterized phenomenon in pharmacological research. This may reflect biological differences, such as in organ and tissue proportions, body fluid distribution, and protein composition of serum, all of which are factors that may contribute to such variations [6, 11]. As with all antipsychotic drugs, risperidone’s pharmacodynamics and pharmacokinetics are influenced by multiple factors including
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