title: Does the medication pattern reflect the CYP2D6 genotype in patients with diagnoses within the schizophrenic spectrum?
abstract: BACKGROUND
  Cytochrome P450 2D6 enzyme (CYP2D6) is an important metabolic pathway for many antipsychotics. Its genetic polymorphism causes pharmacokinetic variability that might lead to adverse drug reactions or treatment failure unless countered by appropriate dose adjustments or shift to CYP2D6-independent antipsychotics.
  
  
  OBJECTIVE
  To investigate the clinical impact of CYP2D6 genotype in patients with a diagnosis within the schizophrenic spectrum using medication pattern as proxy for therapeutic and side effect.
  
  
  METHODS
  The study was conducted in patients genotyped during an inpatient stay (N = 576). Continuous antipsychotic, adjuvant, and anticholinergic drug regimens were registered retrospectively in a cross-sectional manner before genotyping. Antipsychotics were divided into CYP2D6 dependent and independent, and dose equivalents were calculated as chlorpromazine equivalents (CPZEq).
  
  
  RESULTS
  Poor metabolizers and ultrarapid metabolizers were treated with significantly higher median CPZEq doses (625.8; inter quartile range [IQR], 460.4-926.7; and 550; IQR, 199.8-1049) than extensive metabolizers (EMs) and intermediate metabolizers (IMs) (384; IQR, 150-698; and 446; IQR, 150-800) (P = 0.018). Logistic regression showed no association between anticholinergic treatment and CYP2D6 genotype or concomitant treatment with CYP2D6 inhibitors (P = 0.79 and P = 0.46, respectively).
  
  
  CONCLUSIONS
  Our results indicate that CYP2D6 genotype has no sufficient clinical impact that poor metabolizers and ultrarapid metabolizers are easily clinically identified with.
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg University Hospital, Copenhagen, Denmark. gjyr0002@bbh.regionh.dk
authors.forename: Gesche
authors.initials: G
authors.lastname: Jürgens
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Kim
authors.initials: K
authors.lastname: Dalhoff
authors.forename: Merete
authors.initials: M
authors.lastname: Nordentoft
authors.forename: Stig E
authors.initials: SE
authors.lastname: Andersen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002746:Chlorpromazine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D002746:Chlorpromazine