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

Abstract

Aim: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-inhibitorsinduced nausea as its formulation allows more distal gastrointestinal absorption than the paroxetine immediate-release (IR) formulation. Methods: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.Results: 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%). Conclusion: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.

Safety and effectiveness of controlled-release paroxetine in routine clinical practice: results of&nbsp;a&nbsp;postmarketing surveillance study of patients with depression

“…The most common ADRs reported in the first 2 weeks were gastrointestinal disorders such as nausea, and nervous system disorders such as somnolence. This ADR profile was consistent with that reported by a clinical study of paroxetine CR 11 and the postmarketing surveillance of paroxetine IR in patients with depression and panic disorder. 24…”

“…The common ADRs of nausea and somnolence found in this study were generally consistent with those reported by a previous clinical study. 11 Most of the reported ADRs were not serious, and all serious ADRs, except for bipolar disorder, had resolved or were resolving. Although further accumulation of safety data is required for rare events, the overall data revealed no new issues/concerns.…”

“…Paroxetine hydrochloride hydrate controlled-release tablets (GlaxoSmithKline K.K., Tokyo, Japan; hereafter, referred to as paroxetine CR) are a controlled-release formulation of paroxetine, an SSRI antidepressant. 11 This enteric, film-coated, controlled-release formulation allows for the slow dissolution and gradual release of paroxetine only after the tablets have passed the stomach. 12 , 13 Because of these characteristics, the drug can avoid the excessive exposure of paroxetine in the upper gastrointestinal tract, which is related to gastrointestinal symptoms such as nausea.…”

Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta‐analysis

“…All were phase II or III trials aiming at regulatory approval. Of these, four companies have agreed to provide the requested data representing six trials examining five antidepressants; three companies have provided anonymised individual‐level data for four trials examining duloxetine, escitalopram, mirtazapine and paroxetine , and one provided access to such data for two trials examining bupropion and paroxetine at their dedicated internet portal.…”

Qualitative treatment-subgroup interactions in the antidepressant treatment of major depression: Application of QUINT to individual participant data from seven placebo-controlled randomized controlled trials

“…Of these, five companies have agreed to provide the requested data representing six trials examining six antidepressants. Three companies have provided anonymized individual-level data for four trials examining duloxetine, escitalopram, mirtazapine and paroxetine [16,17,18,22], whereas one provided access to such data for two trials examining bupropion and paroxetine [14,23] and another company for a trial examining venlafaxine [15] at their dedicated internet portal only. We used all data that were included in the regulatory submission and the clinical study report of these trials.…”