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Open Access 01-12-2023 | Suicide | Protocol

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

Authors: Caroline Kamp Jørgensen, Sophie Juul, Faiza Siddiqui, Mark Abie Horowitz, Joanna Moncrieff, Klaus Munkholm, Michael Pascal Hengartner, Irving Kirsch, Christian Gluud, Janus Christian Jakobsen

Published in: Systematic Reviews | Issue 1/2023

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 We will search for published and unpublished trials in major medical databases and trial registers.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 We will include published or unpublished randomised clinical trial comparing venlafaxine or mirtazapine with ‘active placebo’, placebo, or no intervention for adults with major depressive disorder.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.

Available only for authorised users

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Title: 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
Authors: Caroline Kamp Jørgensen
Sophie Juul
Faiza Siddiqui
Mark Abie Horowitz
Joanna Moncrieff
Klaus Munkholm
Michael Pascal Hengartner
Irving Kirsch
Christian Gluud
Janus Christian Jakobsen
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Suicide
Antidepressant Drugs
Suicide
Antidepressant Drugs
Mirtazapine
Venlafaxine
Mirtazapine
Published in: Systematic Reviews / Issue 1/2023
Electronic ISSN: 2046-4053
DOI: https://doi.org/10.1186/s13643-023-02221-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Discussion

Systematic review registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Systematic review registration

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