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Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial

Published online by Cambridge University Press:  14 January 2020

Le Xiao
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
Xuequan Zhu
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
Amy Gillespie
Affiliation:
Department of Psychiatry, University of Oxford, Oxford, UK
Yuan Feng
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
Jingjing Zhou
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
Xu Chen
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
Yuanyuan Gao
Affiliation:
Department of Psychiatry, The First Hospital of Hebei Medical University, Hebei, China
Xueyi Wang
Affiliation:
Department of Psychiatry, The First Hospital of Hebei Medical University, Hebei, China
Xiancang Ma
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
Chengge Gao
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
Yunshi Xie
Affiliation:
Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
Xiaoping Pan
Affiliation:
Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
Yan Bai
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
Xiufeng Xu
Affiliation:
Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
Gang Wang
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
Runsen Chen
Affiliation:
The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China Department of Psychiatry, University of Oxford, Oxford, UK
Corresponding

Abstract

Background

This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.

Methods

This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.

Results

A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.

Conclusions

After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

Type
Original Articles
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial
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Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial
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Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial
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