There is considerable variability in the rate of response and remission following treatment with
antidepressant drugs or placebo in depression patients. No pharmacogenetic studies of
bupropion response have been done. We investigated 532 tagging single nucleotide polymorphisms (SNPs) in 34 candidate genes for association with remission and response to either
bupropion (n=319) or placebo (n=257) in patients with
major depressive disorder. Analyses were performed using conditional logistic regression. Significant association (gene-wide correction) was observed for remission following treatment with
bupropion for a SNP within the
serotonin receptor 2A gene (HTR2A rs2770296, p(corrected)=0.02). Response to
bupropion treatment was significantly associated with a SNP in the
dopamine transporter gene (rs6347, p(corrected)=0.013). Among the patients who received placebo, marginal association for remission was observed between a SNP in HTR2A (rs2296972, p(corrected)=0.055) as well as in the
serotonin transporter gene (5-HTT or SLC6A4 rs4251417, p(corrected)=0.050). Placebo response was associated with SNPs in the
glucocorticoid receptor gene (NR3C1; rs1048261, p(corrected)=0.040) and
monoamine oxidase A gene (MAOA; rs6609257, p corrected=0.046). Although the above observations were significant after gene-wide corrections, none of these would be significant after a more conservative study-wide correction for multiple tests. These results suggest a possible role for HTR2A in remission to
bupropion treatment. In accordance with
bupropion pharmacology,
dopamine transporter may play a role in response. The MAOA gene may be involved in placebo response.