title: Influence of the CYP2D6 isoenzyme in patients treated with venlafaxine for major depressive disorder: clinical and economic consequences.
abstract: BACKGROUND
  Antidepressant drugs are the mainstay of drug therapy for sustained remission of symptoms. However, the clinical results are not encouraging. This lack of response could be due, among other causes, to factors that alter the metabolism of the antidepressant drug.
  
  
  OBJECTIVE
  to evaluate the impact of concomitant administration of CYP2D6 inhibitors or substrates on the efficacy, tolerability and costs of patients treated with venlafaxine for major depressive disorder in clinical practice.
  
  
  METHODS
  We designed an observational study using the medical records of outpatients. Subjects aged ≥ 18 years who started taking venlafaxine during 2008-2010 were included. Three study groups were considered: no combinations (reference), venlafaxine-substrate, and venlafaxine-inhibitor. The follow-up period was 12 months. The main variables were: demographic data, comorbidity, remission (Hamilton <7), response to treatment, adverse events and costs. The statistical analysis included logistic regression models and ANCOVA, with p values <0.05 considered significant.
  
  
  RESULTS
  A total of 1,115 subjects were recruited. The mean age was 61.7 years and 75.1% were female. Approximately 33.3% (95% CI: 30.5 to 36.1) were receiving some kind of drug combination (venlafaxine-substrate: 23.0%, and venlafaxine-inhibitor: 10.3%). Compared with the venlafaxine-substrate and venlafaxine-inhibitor groups, patients not taking concomitant drugs had a better response to therapy (49.1% vs. 39.9% and 34.3%, p<0.01), greater remission of symptoms (59.9% vs. 50.2% and 43.8%, p<0.001), fewer adverse events (1.9% vs. 7.0% and 6.1%, p<0.05) and a lower mean adjusted cost (€2,881.7 vs. €4,963.3 and €7,389.1, p<0.001), respectively. All cost components showed these differences.
  
  
  CONCLUSIONS
  The patients treated with venlafaxine alone showed a better response to anti-depressant treatment, greater remission of symptoms, a lower incidence of adverse events and lower healthcare costs.
authors.affiliation: Directorate of Planning, Badalona Serveis Assistencials, S.A., Badalona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Sicras-Mainar
authors.affiliation: Pfizer, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Guijarro
authors.affiliation: Pfizer, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Armada
authors.affiliation: Department of Psychiatry, Badalona Serveis Assistencials, S.A., Badalona, Barcelona, Spain.
authors.forename: Milagrosa
authors.initials: M
authors.lastname: Blanca-Tamayo
authors.affiliation: Medical Documentation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Navarro-Artieda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology*; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000191:economics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D007527:Isoenzymes; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6