Influence of organic cation transporter 3 (SLC22A3) genetic polymorphisms on antidepressant maintenance doses in Japanese patients with depression

Inter-individual variations in antidepressant dosages required to achieve and maintain a therapeutic response are common. To mitigate the risk of recurrence, it is recommended that patients maintain treatment at a dose that effectively alleviates their acute depressive symptoms for at least 6 months. This study investigated the relationship between the antidepressant doses used for maintenance therapy and genetic polymorphisms that affect serotonin transporter activity. Eighty-four Japanese patients with depression were enrolled in the study. For each patient, the doses of antidepressant and anxiolytic/hypnotic medications were quantified as equivalents of imipramine and diazepam, respectively, based on the most recent prescription. Patients were divided into high- and low-dose antidepressant treatment groups, using the median dose as the between-group cutoff. We examined the influence of genetic polymorphisms on inclusion in the high- and low-dose groups. Multivariate logistic regression analysis revealed that the presence of the G allele in the SLC22A3 rs2292334 polymorphism was associated with an increased antidepressant maintenance dose. The odds ratio for an increased presence in the G allele of the SLC22A3 rs2292334 polymorphism was 8.867 (95% confidence interval, 1.869-42.069). These findings have potential use in informing future dosing strategies in depression therapy.