Paroxetine controlled‐release formulation in the treatment of major depressive disorder: A randomized, double‐blind, placebo‐controlled study in Japan and Korea

Abstract

The main purpose of this study was to evaluate the efficacy of paroxetine controlled-release (CR) formulation compared to placebo. A secondary objective was to test the hypothesis that the CR decreases selective-serotonin-reuptake-inhibitors-induced nausea as its formulation allows more distal gastrointestinal absorption than the paroxetine immediate-release (IR) formulation. We conducted this study in Japanese and Korean patients with major depressive disorder (MDD) in order to demonstrate the efficacy and safety of paroxetine CR compared with placebo. The primary efficacy end-point was the adjusted mean change from baseline in the 17-item Hamilton Rating Scale for Depression total score at Week 8. A total of 416 patients with MDD were randomly assigned to the CR, IR and placebo groups. The mean change from baseline in the 17-item Hamilton Rating Scale for Depression was -12.8 in the CR group, -12.5 in the IR group, and -10.4 in the placebo group, which showed a statistically significant difference compared to placebo in CR (P < 0.001) and IR (P = 0.015). The incidence of adverse events was 65% in CR, 69% in IR and 55% in placebo. The adverse events were mostly mild or moderate in severity. In the early treatment period, when initiated from 12.5 mg, the incidence of nausea in the CR group was 6%, which was comparable with that of placebo (5%). Paroxetine CR is efficacious in the acute treatment of MDD and may have the potential benefit of decreasing the incidence of nausea in the early treatment period.