title: An observational study of Venlafaxine and CYP2D6 in clinical practice.
abstract: BACKGROUND
  Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting.
  
  
  METHODS
  47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed.
  
  
  RESULTS
  CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability.
  
  
  CONCLUSIONS
  PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.
authors.forename: R
authors.initials: R
authors.lastname: Rolla
authors.forename: Carla
authors.initials: C
authors.lastname: Gramaglia
authors.forename: Valentina
authors.initials: V
authors.lastname: Dalò
authors.forename: Francesca
authors.initials: F
authors.lastname: Ressico
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Prosperini
authors.forename: Matteo
authors.initials: M
authors.lastname: Vidali
authors.forename: Silvia
authors.initials: S
authors.lastname: Meola
authors.forename: Paola
authors.initials: P
authors.lastname: Pollarolo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.forename: Eugenio
authors.initials: E
authors.lastname: Torre
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zeppegno
mesh_terms: D000328:Adult; D000368:Aged; D003511:Cyclohexanols / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010818:Practice Patterns, Physicians'; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6