title: Failure to respond to treatment with typical antipsychotics is not associated with CYP2D6 ultrarapid hydroxylation.
abstract: OBJECTIVE
  To investigate whether or not there is a correlation between failure to respond to typical antipsychotics and CYP2D6 ultrarapid metaboliser status.
  
  
  METHODS
  CYP2D6 phenotype (metaboliser status) was assigned following genotyping for gene duplication, as well as for the CYP2D6*3, CYP2D6*4, and CYP2D6*5 null alleles in 235 treatment-refractory patients and 73 nonrefractory patients.
  
  
  RESULTS
  Four (1.7%) of the 235 treatment-refractory subjects were positive on the duplication assay, but, of these, two were found to represent duplications of a null allele (CYP2D6*4 ), therefore leaving only two (0.85%) positive for duplication of a wild type allele (ultrarapid metabolisers). Three (4.1%) of the nonrefractory subjects had a genotype consistent with ultrarapid metaboliser status. Fisher's exact test gave a two-tailed P value of 0.091, i.e. a trend towards an excess of ultrarapid metabolisers in the nonrefractory group, which was in the opposite direction to that predicted by our hypothesis.
  
  
  CONCLUSIONS
  Although the results show a trend towards an excess of ultrarapid metabolisers in the nonrefractory group, the percentages in the two groups of patients are both within the range for ultrarapid metabolisers in Caucasian populations. Our data are not consistent with ultrarapid metaboliser status being a major cause of failure to respond to typical antipsychotics.
authors.affiliation: Section Clinical Neuropharmacology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Aitchison
authors.forename: J
authors.initials: J
authors.lastname: Munro
authors.forename: P
authors.initials: P
authors.lastname: Wright
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: A J
authors.initials: AJ
authors.lastname: Makoff
authors.forename: C
authors.initials: C
authors.lastname: Sachse
authors.forename: P C
authors.initials: PC
authors.lastname: Sham
authors.forename: R M
authors.initials: RM
authors.lastname: Murray
authors.forename: D A
authors.initials: DA
authors.lastname: Collier
authors.forename: R W
authors.initials: RW
authors.lastname: Kerwin
mesh_terms: D000483:Alleles; D014150:Antipsychotic Agents / Q000378:metabolism / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology; D017211:Treatment Failure
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6