title: The AmpliChip® CYP450 test and response to treatment in schizophrenia and obsessive compulsive disorder: a pilot study and focus on cases with abnormal CYP2D6 drug metabolism.
abstract: OBJECTIVE
  Genetic factors can result in variance in drug metabolism enzyme function, which is one major mechanism impacting on interindividual variability in response and side effects. We therefore performed a pilot study to investigate genetic variants in the drug metabolizing enzymes CYP2D6 and CYP2C19.
  
  
  METHODS
  We evaluated 35 schizophrenic and 39 obsessive compulsive disorder (OCD) patients treated with various antipsychotics and antidepressants. Patients were assessed for treatment response and side effects. Genotyping for CYP2D6 and CYP2C19 was performed using the AmpliChip(®). Statistical analysis was performed using analysis of variance and Fisher's exact test. Cases of poor metabolizers (PMs) or ultrarapid metabolizers (UMs) were examined in further detail to assess medication outcomes.
  
  
  RESULTS
  Statistical analysis identified no overall significant association of CYP2D6 metabolizer status with treatment response or occurrence of side effects. Nonetheless, case reports of PM and UM individuals indicated lack of response and/or occurrence of side effects in most of these patients. A secondary analysis comparing OCD subjects with impaired 2D6 function to extensive metabolizers was significant (p=0.021).
  
  
  CONCLUSIONS
  Although not conclusive, there was some association between CYP2D6 impaired metabolic status and medication response. Our case reports suggest a potential clinical benefit of CYP genotyping for specific patients. Further validation of CYP2D6 and CYP2C19 testing in prospective, randomized trials is warranted.
authors: Pharmacogenetics Research Clinic, Neurogenetics Section, Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. daniel_mueller@camh.net
authors: Daniel J
authors: DJ
authors: Müller
authors: Eva J
authors: EJ
authors: Brandl
authors: Rudi
authors: R
authors: Hwang
authors: Arun K
authors: AK
authors: Tiwari
authors: Jessica E
authors: JE
authors: Sturgess
authors: Clement C
authors: CC
authors: Zai
authors: Jeffrey A
authors: JA
authors: Lieberman
authors: James L
authors: JL
authors: Kennedy
authors: Margaret A
authors: MA
authors: Richter
mesh_terms: D000328:Adult; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000201:enzymology; D010865:Pilot Projects; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D019389:Cytochrome P-450 CYP2D6