CYP2D6 and Antipsychotic Treatment Outcomes in Children and Youth: A Systematic Review.

ABSTRACT

Objective: To systematically review the impact of CYP2D6 genetic variation on antipsychotic pharmacokinetics, efficacy, and adverse drug reactions among children and youth. Method: The published literature was systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations and critically evaluated using standardized tools and consensus criteria. Results: A total of 20 eligible studies comprising 1078 children and youth were evaluated. The included studies were of fair to moderate quality and included mostly males, individuals of European ancestry, and those treated with risperidone. CYP2D6 poor metabolizers (PMs) were consistently shown to have increased concentrations of risperidone relative to normal metabolizers (NMs). PMs were also consistently shown to have a greater propensity to experience antipsychotic (primarily risperidone) associated adverse drug reactions relative to NMs. However, robust evidence for an association between CYP2D6 and efficacy was less apparent. Conclusion and Clinical Significance: The current knowledge base suggests that CYP2D6 genetic variation has an appreciable impact on antipsychotic pharmacokinetics and the propensity for adverse drug reactions, particularly among children receiving risperidone treatment. However, several limitations with the current literature (e.g., sample sizes, study design, sample heterogeneity) should be addressed in future studies. Assuming that future studies support the link between CYP2D6 genetic variation and antipsychotic outcomes, we would anticipate an increase in the implementation of CYP2D6-guided antipsychotic drug selection and dose optimization in child and adolescent psychiatric services.