title: The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation.
abstract: OBJECTIVE
  To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources.
  
  
  METHODS
  The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members.
  
  
  METHODS
  A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out.
  
  
  RESULTS
  For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99-100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing.
  
  
  CONCLUSIONS
  Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, UK.
authors.forename: N
authors.initials: N
authors.lastname: Fleeman
authors.forename: C
authors.initials: C
authors.lastname: McLeod
authors.forename: A
authors.initials: A
authors.lastname: Bagust
authors.forename: S
authors.initials: S
authors.lastname: Beale
authors.forename: A
authors.initials: A
authors.lastname: Boland
authors.forename: Y
authors.initials: Y
authors.lastname: Dundar
authors.forename: A
authors.initials: A
authors.lastname: Jorgensen
authors.forename: K
authors.initials: K
authors.lastname: Payne
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: S
authors.initials: S
authors.lastname: Pushpakom
authors.forename: T
authors.initials: T
authors.lastname: Walley
authors.forename: P
authors.initials: P
authors.lastname: de Warren-Penny
authors.forename: R
authors.initials: R
authors.lastname: Dickson
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005820:Genetic Testing / Q000191:economics*; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy* / Q000191:economics / Q000235:genetics*; D013222:State Medicine / Q000191:economics
chemical_list: D014150:Antipsychotic Agents; D003577:Cytochrome P-450 Enzyme System