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Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein β3 subunit as predictors of response to fluoxetine and nortriptyline

Peter R. Joyce, Roger T. Mulder, Suzanne E. Luty, Janice M. McKenzie, Allison L. Miller, Geraldine R. Rogers, Martin A. Kennedy
DOI: http://dx.doi.org/10.1017/S1461145703003663 339-346 First published online: 1 December 2003

Abstract

In 169 depressed patients randomized to treatment with either fluoxetine or nortriptyline, we examined whether polymorphisms of the serotonin transporter and the G protein β3 subunit influenced response to these antidepressants. For depressed patients under the age of 25 yr the T allele of the G protein β3 subunit was associated with a markedly poorer response to nortriptyline, while serotonin transporter polymorphisms did not predict antidepressant response. However, in patients 25 yr or older, the G protein β3 polymorphisms did not predict antidepressant response, while the s,s genotype of the serotonin transporter was associated with a poorer response to both fluoxetine and nortriptyline. These differential pharmacogenetic predictors of antidepressant response by age, may provide clues to understanding the discontinuities in pharmacological responsiveness of child/adolescent and adult depressive disorders.

Key words
  • Antidepressants
  • G protein β3 subunit
  • pharmacogenomics
  • serotonin transporter