Evidence map›Paper›PMID 30381374›Full record

Trial reportBMJ (Clinical research ed.)2018

Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR).

David S Kessler, Stephanie J MacNeill, Deborah Tallon, Glyn Lewis, Tim J Peters, William Hollingworth, Jeff Round, Alison Burns, Carolyn A Chew-Graham, Ian M Anderson and 9 more

Erratum issuedOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMJ (Clinical research ed.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 7 pooled it
7.3field-weighted citation impact, top 2% 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

33 citing papers in PubMed, 7 syntheses or guidelines pooled it, 79 citations in OpenAlex.

  1. Pooled it
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  7. Pharmacological interventions for treatment-resistant depression in adults.The Cochrane database of systematic reviews · 2019
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  18. Review
  19. Thoughtful prescribing for patients with difficult-to-treat depression.Canadian family physician Medecin de famille canadien · 2023
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  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 2 countries.

David S KesslerPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK david.kessler@bristol.ac.uk.ORCID 0000-0001-5333-132X
Stephanie J MacNeillBristol Randomised Trials Collaboration, Population Health Sciences, Bristol Medical School, Bristol, UK.
Deborah TallonPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK.
Glyn LewisDivision of Psychiatry, University College London, London, UK.
Tim J PetersPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK.
William HollingworthPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK.
Jeff RoundPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK.
Alison BurnsPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK.
Carolyn A Chew-GrahamPrimary Care and Health Sciences, Keele University, Keele, UK.
Ian M AndersonDivision of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.
Tom ShepherdPrimary Care and Health Sciences, Keele University, Keele, UK.
John CampbellExeter Medical School, University of Exeter, Exeter, UK.
Chris M DickensExeter Medical School, University of Exeter, Exeter, UK.
Mary CarterExeter Medical School, University of Exeter, Exeter, UK.
Caroline JenkinsonExeter Medical School, University of Exeter, Exeter, UK.
Una MacleodHull York Medical School, Hull, UK.
Helen GibsonHull York Medical School, Hull, UK.
Simon DaviesCentre for Addiction and Mental Health, Toronto, Canada.
Nicola J WilesPopulation Health Sciences, Bristol Medical School, Bristol BS8 2BN, UK.
University of Exeter · GBAt Bristol · GBHull York Medical School · GBKeele University · GBCentre for Addiction and Mental Health · CAUniversity College London · GBUniversity of Manchester · GB

Funding

Department of Health 11/129/76
6 · The paper itself

Abstract

objectiveTo investigate the effectiveness of combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants for treatment resistant depression in primary care.

designTwo parallel group multicentre phase III randomised placebo controlled trial.

setting106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015.

participants480 adults aged 18 or more years who scored 14 or more on the Beck depression inventory, second revision, fulfilled ICD-10 (international classification of diseases, 10th revision) criteria for depression, and had used an SSRI or SNRI for at least six weeks but were still depressed. 241 were randomised to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment. Participants were stratified by centre and minimised by baseline Beck depression inventory score, sex, and current psychological therapy. They were followed up at 12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12 week follow-up.

main outcome measuresDepressive symptoms at 12 weeks after randomisation, measured using the Beck depression inventory II score as a continuous variable. Secondary outcomes included measures of anxiety, quality of life, and adverse effects at 12, 24, and 52 weeks.

resultsBeck depression inventory II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline scores and minimisation or stratification variables, although the confidence interval included the null (mean (SD) scores at 12 weeks: 18.0 (12.3) in the mirtazapine group, 19.7 (12.4) in the placebo group; adjusted difference between means -1.83 (95% confidence interval -3.92 to 0.27); P=0.09). Adverse effects were more common in the mirtazapine group and were associated with the participants stopping the trial drug.

conclusionThis study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where evidence of effective treatment options is limited.

trial registrationCurrent Controlled Trials ISRCTN06653773.

Indexed as

AdolescentAdultAgedAntidepressive AgentsDepressive Disorder, Treatment-ResistantDrug Therapy, CombinationEnglandFemaleGeneral PracticeHumansMaleMiddle AgedMirtazapineSelective Serotonin Reuptake InhibitorsSerotonin and Noradrenaline Reuptake InhibitorsTreatment OutcomeAntidepressive AgentsMirtazapineSelective Serotonin Reuptake InhibitorsSerotonin and Noradrenaline Reuptake Inhibitors

Identifiers

PMID30381374
PMCPMC6207929
OpenAlexW2899074813

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.