title: Influence of combinations of drugs that act on the CYP2D6 metabolic pathway in the treatment of major depressive disorder: a population-based study.
abstract: OBJECTIVE
  To describe the frequency of drug combinations (substrate-substrate or substrate-inhibitor) with the potential to interfere with the CYP2D6 metabolic pathway in patients receiving antidepressant medication for major depressive disorder.
  
  
  METHODS
  We carried out an observational study using outpatient medical records. We included adult subjects who initiated antidepressant medication during 2008-2010. Patients were assigned to three study groups: no combination, substrate-substrate, and substrate-inhibitor. Follow-up period was 12 months.
  
  
  METHODS
  demographics, comorbidity and medication persistence. Statistical analysis included a logistic regression model, P<0.05.
  
  
  RESULTS
  Five thousand six hundred and thirty patients were recruited (61.9 years, 76.9% female), 24.4% (CI: 23.8 - 26.0%) received some kind of drug combination (substrate-substrate: 15.4%, substrate-inhibitor: 9.0%). Variables significantly associated with drugs combinations that may act on the CYP2D6 metabolic pathway were: dementia (OR=4.2), neuropathy (OR=4.2) and stroke (OR=1.9), P<0.001. Medication persistence at 12 months was longer in patients with no combination (55.3%) than in patients receiving substrate-substrate (50.5%) or substrate-inhibitor (45.0%) combinations, P<0.001.
  
  
  CONCLUSIONS
  Twenty-five percent of major depressive disorder patients received a combination of drugs with the potential to interfere with CYP2D6 metabolic pathway. These combinations increased with comorbidity and resulted in shorter medication persistence of antidepressant treatment.
authors: Department of Planning, Badalona Serveis Assistencials SA, Badalona, Barcelona, Spain. Electronic address: asicras@bsa.cat.
authors: A
authors: A
authors: Sicras-Mainar
authors: Health Economics & Outcomes Research Manager, Pfizer, Madrid, Spain.
authors: P
authors: P
authors: Guijarro
authors: Medical Advisor, Pfizer, Madrid, Spain.
authors: B
authors: B
authors: Armada
authors: Department of Psychiatry, Badalona Serveis Assistencials SA, Badalona, Barcelona, Spain.
authors: M
authors: M
authors: Blanca-Tamayo
authors: Medical Documentation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: R
authors: R
authors: Navarro-Artieda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; Comorbidity; Major depression; Substrate-inhibitor; Substrate-substrate