文拉法辛和米氮平与“活性安慰剂”、安慰剂或不干预治疗成人重度抑郁症的不良事件风险：两项分别进行的系统评价和试验序贯分析的协议。

The risks of adverse events with venlafaxine and mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder: a protocol for two separate systematic reviews with meta-analysis and Trial Sequential Analysis.

机构信息

Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.

Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, J.B. Winsløws Vej 19, 3, Odense C, 5000, Odense, Denmark.

出版信息

Syst Rev. 2023 Mar 30;12(1):57. doi: 10.1186/s13643-023-02221-5.

DOI:10.1186/s13643-023-02221-5

PMID:36991504

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10061867/

Abstract

BACKGROUND

Major depressive disorder causes a great burden on patients and societies. Venlafaxine and mirtazapine are commonly prescribed as second-line treatment for patients with major depressive disorder worldwide. Previous systematic reviews have concluded that venlafaxine and mirtazapine reduce depressive symptoms, but the effects seem small and may not be important to the average patient. Moreover, previous reviews have not systematically assessed the occurrence of adverse events. Therefore, we aim to investigate the risks of adverse events with venlafaxine or mirtazapine versus 'active placebo', placebo, or no intervention for adults with major depressive disorder in two separate systematic reviews.

METHODS

This is a protocol for two systematic reviews with meta-analysis and Trial Sequential Analysis. The assessments of the effects of venlafaxine or mirtazapine will be reported in two separate reviews. The protocol is reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols, risk of bias will be assessed with the Cochrane risk-of-bias tool version 2, clinical significance will be assessed using our eight-step procedure, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. We will search for published and unpublished trials in major medical databases and trial registers. Two review authors will independently screen the results from the literature searches, extract data, and assess risk of bias. We will include published or unpublished randomised clinical trial comparing venlafaxine or mirtazapine with 'active placebo', placebo, or no intervention for adults with major depressive disorder. The primary outcomes will be suicides or suicide attempts, serious adverse events, and non-serious adverse events. Exploratory outcomes will include depressive symptoms, quality of life, and individual adverse events. If feasible, we will assess the intervention effects using random-effects and fixed-effect meta-analyses.

DISCUSSION

Venlafaxine and mirtazapine are frequently used as second-line treatment of major depressive disorder worldwide. There is a need for a thorough systematic review to provide the necessary background for weighing the benefits against the harms. This review will ultimately inform best practice in the treatment of major depressive disorder.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO CRD42022315395.

摘要

背景

重度抑郁症给患者和社会带来了巨大负担。文拉法辛和米氮平是全球范围内常用于治疗重度抑郁症的二线药物。先前的系统评价得出结论，文拉法辛和米氮平可减轻抑郁症状，但效果似乎较小，对普通患者可能并不重要。此外，先前的综述并未系统评估不良事件的发生情况。因此，我们旨在通过两项系统评价和荟萃分析及序贯分析来调查文拉法辛或米氮平与“活性安慰剂”、安慰剂或不干预治疗成人重度抑郁症的不良事件风险。

方法

这是两项系统评价和荟萃分析及序贯分析的方案。文拉法辛或米氮平的效果评估将在两项单独的综述中报告。该方案按照系统评价和荟萃分析方案的首选报告项目进行报告，使用 Cochrane 偏倚风险工具版本 2 评估风险，使用我们的八步程序评估临床意义，并使用推荐分级评估、制定与评价方法评估证据的确定性。我们将在主要医学数据库和试验登记处中搜索已发表和未发表的试验。两名综述作者将独立筛选文献检索结果、提取数据并评估偏倚风险。我们将纳入比较文拉法辛或米氮平与“活性安慰剂”、安慰剂或不干预治疗成人重度抑郁症的已发表或未发表的随机临床试验。主要结局将是自杀或自杀企图、严重不良事件和非严重不良事件。探索性结局将包括抑郁症状、生活质量和个体不良事件。如果可行，我们将使用随机效应和固定效应荟萃分析评估干预效果。