title: SLC6A2 and SLC6A4 variants interact with venlafaxine serum concentrations to influence therapy outcome.
abstract: OBJECTIVE
  The effects of genetic variants in genes encoding the target structures of antidepressants on the therapeutic efficacy of antidepressant drugs have been investigated with unconclusive results. One possible confounding factor in most studies was the fact that drug serum concentrations had not been determined.
  
  
  METHODS
  Within a clinical setting, 56 inpatients suffering from depressive episodes in the context of either major depressive disorder or bipolar affective disorder were studied. Response to venlafaxine was assessed after 4 weeks of treatment and correlated to serum concentration and functional variants in genes encoding the norepinephrine (SLC6A2; rs28386840) and the serotonin transporter (SLC6A4; [5-HTTLPR], rs25531). Symptom change was evaluated using the Clinical Global Impression-Improvement (CGI-I) scale.
  
  
  RESULTS
  No association between therapeutic response, venlafaxine serum concentration (active moiety) and rs28386840 was found. In carriers of the high expressing SLC6A4 genotype (lAlA-), a poor response to venlafaxine was found significantly more often. In subsamples stratified for serum concentration this held true for patients with serum concentrations between 201 and 400 ng/mL (n=21), while in patients with sub- (≤ 200 ng/mL; n=12) and supra-recommended (> 400 ng/mL; n=23) concentrations, no significant differences were observed.
  
  
  CONCLUSIONS
  The observed association is consistent with findings of some previous studies, whereas others showed differing results highlighting the need for further investigations.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Proft
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Kopf
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Olmes
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hempel
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Deckert
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Pfuhlmann
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reif
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Unterecker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000928:Antidepressive Agents / Q000097:blood* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003511:Cyclohexanols / Q000097:blood* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000069468:Desvenlafaxine Succinate; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human