title: Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses.
abstract: There is wide variability in the response of individuals to standard doses of antipsychotic drugs. It has been suggested that this may be partly explained by differences in the cytochrome P450 (CYP450) enzyme system responsible for metabolizing the drugs. We conducted a systematic review and meta-analyses to consider whether testing for CYP450 single nucleotide polymorphisms in adults starting antipsychotic treatment for schizophrenia predicts and leads to improvements in clinical outcomes. High analytic validity in terms of sensitivity and specificity was seen in studies reporting P450 testing. However, there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy, although there was an association between CYP2D6 genotype and extrapyramidal adverse effects. No studies reported on the prospective use of CYP2D6 genotyping tests in clinical practice. In conclusion, evidence of clinical validity and utility of CYP2D6 testing in patients being prescribed antipsychotics is lacking, and thus, routine pharmacogenetic testing prior to antipsychotic prescription cannot be supported at present. Further research is required to improve the evidence base and to generate data on clinical validity and clinical utility.
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK. nigel.fleeman@liverpool.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Fleeman
authors.forename: Y
authors.initials: Y
authors.lastname: Dundar
authors.forename: R
authors.initials: R
authors.lastname: Dickson
authors.forename: A
authors.initials: A
authors.lastname: Jorgensen
authors.forename: S
authors.initials: S
authors.lastname: Pushpakom
authors.forename: C
authors.initials: C
authors.lastname: McLeod
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: T
authors.initials: T
authors.lastname: Walley
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6