Background: We investigated the relationship between plasma concentrations of paroxetine and the therapeutic effect of the drug, and we evaluated the therapeutic reference range for plasma concentration of paroxetine in patients with major depressive disorders (MDD). Methods: In this study, 120 patients with MDD were treated with 1040 mg/d of paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate the patients at 0, 1, 2, 4, and 6 weeks. At the 6-week treatment time point, the patients were divided into 7 groups according to their paroxetine plasma concentrations in increments of 20 ng/mL. We used an analysis of variance and a chi(2) test to define the therapeutic reference range for plasma paroxetine concentrations. Results: We used 50% as the cutoff values for the percentage of MADRS improvement to determine the responder rates, and we defined remitters as patients with MADRS scores,10 at the 6-week treatment time point. We analyzed the responder and remitter rates of the patients according to their plasma paroxetine concentrations: 20 ng/mL, 40 ng/mL, and 60 ng/mL using the chi(2) test. According to the results of the chi(2) test in the responder rates, the 20-60 ng/mL plasma paroxetine group showed the highest effect size. Conclusions: The results of this study suggested that a range of 20-60 ng/mL is the therapeutic reference range for concentrations of paroxetine in plasma in patients with MDD.