Evidence map›Paper›PMID 36991504›Full record

ArticleSystematic reviews2023

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.

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

Open access · goldAbstract read
In one paragraph

Article in Systematic reviews, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 syntheses or guidelines pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 4 countries.

Caroline Kamp JørgensenCopenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark. caroline.joergensen@ctu.dk.ORCID 0000-0002-7756-4694
Sophie JuulCopenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.
Faiza SiddiquiCopenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.
Mark Abie HorowitzDivision of Psychiatry, University College London, Gower Street, London, WC1E 6BT, England.
Joanna MoncrieffDivision of Psychiatry, University College London, Gower Street, London, WC1E 6BT, England.
Klaus MunkholmMental Health Centre Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Hovedvejen 17, 2000, Frederiksberg, Copenhagen, Denmark.
Michael Pascal HengartnerDepartment of Applied Psychology, Zurich University of Applied Sciences, Pfingstweidstrasse 96, 8005, Zurich, Switzerland.
Irving KirschProgram in Placebo Studies, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
Christian GluudCopenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.
Janus Christian JakobsenCopenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark.
University of Southern Denmark · DKGoodmayes Hospital · GBMental Health Services · DKCopenhagen University Hospital · DKHarvard University · USZHAW Zurich University of Applied Sciences · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMajor 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.

methodsThis 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.

Indexed as

Major Depressive DisorderAdultHumansMeta-Analysis as TopicMirtazapineQuality of LifeReview Literature as TopicVenlafaxine HydrochlorideMirtazapineVenlafaxine HydrochlorideAdverse effectsAdverse eventsAntidepressantsBeneficial effectsMajor depressive disorderMirtazapineVenlafaxine

Identifiers

PMID36991504
PMCPMC10061867
OpenAlexW4361280733

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.