title: ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial.
abstract: OBJECTIVE
  The ABCB1 gene encodes P-glycoprotein, which limits brain concentrations of certain antidepressants. ABCB1 variation has been associated with antidepressant efficacy and side effects in small-sample studies. Cognitive impairment in major depressive disorder predicts poor treatment outcome, but ABCB1 genetic effects in patients with cognitive impairment are untested. The authors examined ABCB1 genetic variants as predictors of remission and side effects in a large clinical trial that also incorporated cognitive assessment.
  
  
  METHODS
  The authors genotyped 10 ABCB1 single-nucleotide polymorphisms (SNPs) in 683 patients with major depressive disorder treated for at least 2 weeks, of whom 576 completed 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine (all substrates for P-glycoprotein) in a large randomized, prospective, pragmatic trial. Antidepressant efficacy was assessed with the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR), and side effects with a rating scale for frequency, intensity, and burden of side effects. General and emotional cognition was assessed with a battery of 13 tests.
  
  
  RESULTS
  The functional SNP rs10245483 upstream from ABCB1 had a significant effect on remission and side effect ratings that was differentially related to medication and cognitive status. Common homozygotes responded better and had fewer side effects with escitalopram and sertraline. Minor allele homozygotes responded better and had fewer side effects with venlafaxine, with the better response most apparent for patients with cognitive impairment.
  
  
  CONCLUSIONS
  The functional polymorphism rs10245483 differentially affects remission and side effect outcomes depending on the antidepressant. The predictive power of the SNP for response or side effects was not lessened by the presence of cognitive impairment.
authors: From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, Calif.; and Brain Resource, Ltd., Sydney, Australia; and Brain Resource, Inc., San Francisco.
authors: Alan F
authors: AF
authors: Schatzberg
authors: From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, Calif.; and Brain Resource, Ltd., Sydney, Australia; and Brain Resource, Inc., San Francisco.
authors: Charles
authors: C
authors: DeBattista
authors: From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, Calif.; and Brain Resource, Ltd., Sydney, Australia; and Brain Resource, Inc., San Francisco.
authors: Laura C
authors: LC
authors: Lazzeroni
authors: From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, Calif.; and Brain Resource, Ltd., Sydney, Australia; and Brain Resource, Inc., San Francisco.
authors: Amit
authors: A
authors: Etkin
authors: From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, Calif.; and Brain Resource, Ltd., Sydney, Australia; and Brain Resource, Inc., San Francisco.
authors: Greer M
authors: GM
authors: Murphy
authors: From the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford; the Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), VA Palo Alto Health Care System, Palo Alto, Calif.; and Brain Resource, Ltd., Sydney, Australia; and Brain Resource, Inc., San Francisco.
authors: Leanne M
authors: LM
authors: Williams
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D020280:Sertraline / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000928:Antidepressive Agents; D003511:Cyclohexanols; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D020280:Sertraline