CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression

Recent advances in oligonucleotide microarray technology ("gene chips") per mit rapid screening for DNA sequence variation. The CYP2D6 gene encodes deb risoquine hydroxylase, which metabolizes the antidepressant nortriptyline a nd other psychotropic medications. Nortriptyline plasma concentrations were obtained after at least three weeks of treatment in 36 geriatric patients with major depression who were taking a mean of 8.6 other medications besid es nortriptyline. Oligonucleotide microarrays were used to detect 16 CYP2D6 alleles that affect debrisoquine hydroxylase activity. Subjects carrying a lleles encoding impaired debrisoquine hydroxylase activity had significantl y greater nortriptyline concentrations and lower nortriptyline doses than d id other subjects. Significant correlations were found between the numbers of alleles encoding decreased metabolism and nortriptyline plasma concentra tion, nortriptyline dose, and nortriptyline plasma concentration standardiz ed for dose, indicating a gene dosage effect. These results demonstrate tha t CYP2D6 genotyping on a microarray platform can be used to predict plasma antidepressant concentrations despite advanced patient age and numerous con current medications, (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.