In this study, we tested the influence of the
serotonin type 2A, 3A and 3B receptor genes (HTR2A, HTR3A, HTR3B) in addition to a polymorphism in the promoter region of the
serotonin transporter (SERTPR), and investigated the different characteristics of clinical responses to
paroxetine and
fluvoxamine. A total of 100 Japanese patients affected by major recurrent depression were enrolled in a randomized 6-week study. The clinical response was evaluated using the Hamilton Rating Scale for Depression (HAM-D), and
adverse drug reactions were assessed at each visit. Patients with the l allele of SERTPR showed a better response to
SSRIs than s/s genotype carriers (p = 0.015-0.042), more significantly to
fluvoxamine. The -1438G/G genotype of HTR2A was associated with a good response to
SSRIs (p = 0.010-0.039), especially to
fluvoxamine, and significantly with severe
nausea in
paroxetine-treated patients (p = 0.013). The 178C/C genotype of the HTR3A was associated with an
antidepressant response (p = 0.022-0.042), and more significantly in
paroxetine-treated patients (p = 0.002-0.042). These effects were independent of one another. We replicated the finding that the SERPTR polymorphism was associated with a response to
SSRIs. We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy, and the HTR2A polymorphism is also associated with
adverse drug reactions. Furthermore, the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI.