title: Pharmacogenetics of risperidone: a systematic review of the clinical effects of CYP2D6 polymorphisms.
abstract: OBJECTIVE
  To summarize and evaluate the pharmacogenetic literature pertaining to the effects of CYP2D6 polymorphism on clinical outcomes of risperidone therapy.
  
  
  METHODS
  A systematic literature search was performed using the search terms risperidone, pharmacogenetics, cytochrome P-450 enzyme system, cytochrome P-450 CYP2D6, and polymorphism (genetic) in MEDLINE (1946-October 2012), EMBASE (1980-October 2012), PubMed (1947-October 2012), International Pharmaceutical Abstracts (1970-October 2012), and Google Scholar.
  
  
  METHODS
  Identified articles were included if they measured the association between CYP2D6 genetic polymorphisms and clinical outcomes in at least 2 patients taking risperidone. The data elements extracted from these articles consisted of study design, number of subjects, indication for risperidone therapy, CYP2D6 phenotype status, mean daily dose of risperidone, and effects on clinical outcomes.
  
  
  RESULTS
  The identified citations consisted of 10 prospective nonrandomized, uncontrolled cohort studies, 1 retrospective cohort study, 1 prospective case-control study, and 1 retrospective case series. Studies were of variable quality and none provided high-quality evidence; they included heterogeneous patient populations with varying clinical diagnoses and drug therapy regimens. Most studies reported nonsignificant trends but were limited by power to detect statistical significance and short trial duration. However, increased risk of adverse effects (including QT interval prolongation) was observed in patients with inactive alleles.
  
  
  CONCLUSIONS
  While there were trends toward increased adverse effects in poor metabolizers, most outcomes were not significant. As such, routine genotyping should not be used for screening. Future usefulness cannot be ruled out, as many studies had significant limitations that preclude determination of clinical relevance. Adequately powered clinical and epidemiologic studies are warranted to clarify the role of CYP2D6 genotyping in practice.
authors: The University of British Columbia, Vancouver, British Columbia, Canada.
authors: Andrea L
authors: AL
authors: Cartwright
authors: Kyle J
authors: KJ
authors: Wilby
authors: Susan
authors: S
authors: Corrigan
authors: Mary H H
authors: MH
authors: Ensom
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D018967:Risperidone / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone