Pharmacogenetics has arrived in clinical psychiatric practice with the FDA approval of the AmpliChip CYP450 Test that genotypes for two cytochrome P450 2D6 (CYP2D6) and 2C19 (CYP2C19) genes. Other pharmacogenetic tests, including those focused on pharmacodynamic genes, are far from ready for clinical application. CYP2D6 is important for the metabolism of many antidepressants and antipsychotics, and CY2C19 is important for some antidepressant metabolism. Poor metabolizers (PMs), lacking the enzyme, account for up to 7% of Caucasians for CYP2D6 and up to 25% of East Asians for CYP2C19. Patients having three or more active CYP2D6 alleles (up to 29% in North Africa and the Middle East), are called CYP2D6 ultra-rapid metabolizers (UMs). CYP2D6 phenotypes (particularly PMs) are probably important in patients taking tricyclic antidepressants (TCAs), venlafaxine, typical antipsychotics, and risperidone. The CYP2C19 PM phenotype is probably important in patients taking TCAs and perhaps citalopram, escitalopram, and sertraline. On the basis of the literature and the authors' clinical experience, the authors provide provisional recommendations for identifying and treating CYP2D6 PMs, CYP2C19 PMs, and CYP2D6 UMs. The next few years will determine whether CYP2D6 genotyping is beneficial for patients taking the new drugs aripiprazole, duloxetine, and atomoxetine. Practical recommendations for dealing with laboratories offering CYP2D6 and CYP2C29 genotyping are provided.
|Number of pages||11|
|State||Published - 2006|
Bibliographical noteFunding Information:
Roche Molecular Systems, Inc. markets the Amplichip CYP450 Test detecting the CYP2D6 and CYP2C19 gene variations. Jose de Leon, M.D., has received support for his laboratory and research-initiated grants from Roche-Molecular Systems, Inc. and has lectured once supported by Roche-Molecular Systems, Inc., but he has not received any consultant payments. He has no other financial arrangements with Roche Molecular Systems, Inc. He has no stocks in Roche, Affymetrix, or any other companies developing pharmacogenetic tests. In the past 2 years, Dr. de Leon has 1) been on the advisory board of Bristol-Myers Squibb; 2) received researcher-initiated grants from Eli Lilly ; and 3) delivered a lecture supported by Eli Lilly (once).
ASJC Scopus subject areas
- Arts and Humanities (miscellaneous)
- Applied Psychology
- Psychiatry and Mental health