Influence of Genetic Polymorphisms and Concomitant Anxiolytic Doses on Antidepressant Maintenance Doses in Japanese Patients with Depression.
To prevent recurrent depression, patients should ideally continue treatment for >6 months with the antidepressant dose that effectively suppressed acute depressive symptoms. However, there are inter-individual differences in the antidepressant doses required to achieve response and maintenance. Therefore, this study was conducted to examine the role of clinical features, including genetic polymorphisms, on the antidepressant dose required for maintenance therapy in 82 Japanese patients with depression. We calculated the antidepressant dose using the imipramine equivalent scale and the dose of concomitant anxiolytics and hypnotics using the diazepam equivalent scale. The 82 participants were classified into two groups based on the median imipramine equivalent dose, and we examined the influence of patient characteristics and the presence of genetic polymorphisms of brain-derived neurotropic factor (BDNF; rs6265) and cyclic adenosine monophosphate responsive element-binding protein 1 (CREB1; rs2253306, rs4675690, rs769963) on the antidepressant maintenance dose. Using a multivariate logistic regression analysis, we found that the concomitant diazepam equivalent dose and presence of the CREB1 rs4675690 polymorphism were significantly associated with the antidepressant maintenance dose. We concluded that these factors influenced the antidepressant dose in maintenance therapy among Japanese patients with depression. However, further research is required in large cohorts.
Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka.
Kazuyuki
K
Inoue
Takuma
T
Murofushi
Kakeru
K
Nagaoka
Natsuko
N
Ando
Yasuhiro
Y
Hakamata
Akiko
A
Suzuki
Akiko
A
Umemura
Yuko
Y
Yoshida
Keita
K
Hirai
Daiki
D
Tsuji
Kunihiko
K
Itoh
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics*; D003975:Diazepam / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C579455:BDNF protein, human; D007099:Imipramine; D003975:Diazepam