title: Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs).
abstract: OBJECTIVE
  To determine if testing for cytochrome P450 (CYP450) polymorphisms in adults entering selective serotonin reuptake inhibitor (SSRI) treatment for non-psychotic depression leads to improvement in outcomes, or if testing results are useful in medical, personal, or public health decisionmaking.
  
  
  METHODS
  We searched MEDLINE, the Cochrane Database of Abstracts of Reviews of Effects, PsychInfo, HealthSTAR, and CINAHL, and reviewed the reference lists of included articles and relevant review articles and meta-analyses for eligible studies. We also included documents from the U.S. Food and Drug Administration (FDA) that could be publicly accessed.
  
  
  METHODS
  We developed an analytic framework and identified key questions to guide the review process. Project-specific inclusion/exclusion criteria were also developed and were used by paired researchers independently to review both abstracts and full-text articles; both researchers were required to agree on inclusion status at the full-text stage. Abstractors evaluated each included article for factors affecting internal and external validity.
  
  
  RESULTS
  A review of 1,200 abstracts led to the final inclusion of 37 articles. The evidence indicates the existence of tests with high sensitivity and specificity for detecting only a few of the more common known polymorphisms of 2D6, 2C19, 2C8, 2C9, and 1A1. There is mixed evidence regarding the association between CYP450 genotypes and SSRI metabolism, efficacy, and tolerability in the treatment of depression, mainly from a series of heterogeneous studies in small samples. There are no data regarding: (a) if testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes versus not testing, or if testing results are useful in medical, personal, or public health decisionmaking; (b) if CYP450 testing influences depression management decisions by patients and providers in ways that could improve or worsen outcomes; or (c) if there are direct or indirect harms associated with testing for CYP450 polymorphisms or with subsequent management options.
  
  
  CONCLUSIONS
  There is a paucity of good-quality data addressing the questions of whether testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression leads to improvement in outcomes, or whether testing results are useful in medical, personal, or public health decisionmaking.
authors.forename: David B
authors.initials: DB
authors.lastname: Matchar
authors.forename: Mugdha E
authors.initials: ME
authors.lastname: Thakur
authors.forename: Iris
authors.initials: I
authors.lastname: Grossman
authors.forename: Douglas C
authors.initials: DC
authors.lastname: McCrory
authors.forename: Lori A
authors.initials: LA
authors.lastname: Orlando
authors.forename: David C
authors.initials: DC
authors.lastname: Steffens
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Cline
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Gray
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D017367:Selective Serotonin Reuptake Inhibitors; C450260:CYP2C9 protein, human; C045793:CYP2C19 protein, human