title: Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients.
abstract: 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.
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, Moriguchi, Japan. pangaea1975@yahoo.co.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Masataka
authors.initials: M
authors.lastname: Wakeno
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fukuda
authors.forename: Gaku
authors.initials: G
authors.lastname: Okugawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ikenaga
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Takekita
authors.forename: Kenji
authors.initials: K
authors.lastname: Nobuhara
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use*; D044348:Receptors, Serotonin, 5-HT2 / Q000235:genetics*; D012189:Retrospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D000928:Antidepressive Agents; D044348:Receptors, Serotonin, 5-HT2; D050486:Serotonin Plasma Membrane Transport Proteins; D017374:Paroxetine; D016666:Fluvoxamine