Evidence map›Paper›PMID 33669254›Full record

ArticleJournal of clinical medicine2021

The Role of Inflammatory Proteins in Anti-Glucocorticoid Therapy for Treatment-Resistant Depression.

Rebecca Strawbridge, Alzbeta Jamieson, John Hodsoll, Ian Nicol Ferrier, Richard Hamish McAllister-Williams, Timothy R Powell, Allan H Young, Anthony J Cleare, Stuart Watson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Observational
  2. Review
  3. Review
  4. Article
  5. Endocrinological Treatment Targets for Depressive Disorder.Advances in experimental medicine and biology · 2024
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
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

9 authors.

Rebecca StrawbridgeDepartment of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, PO74, King's College London, De Crespigny Park, London SE5 8AZ, UK.ORCID 0000-0002-2984-1124
Alzbeta JamiesonDepartment of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, PO74, King's College London, De Crespigny Park, London SE5 8AZ, UK.ORCID 0000-0002-5121-5998
John HodsollNational Institute for Health Research Maudsley Biomedical Research Centre, South London & Maudsley NHS Foundation Trust, London SE5 8AZ, UK.
Ian Nicol FerrierNorthern Centre for Mood Disorders, Translational and Clinical Research Institute, Newcastle University, Newcastle NE4 5PL, UK.
Richard Hamish McAllister-WilliamsNorthern Centre for Mood Disorders, Translational and Clinical Research Institute, Newcastle University, Newcastle NE4 5PL, UK.
Timothy R PowellSocial, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
Allan H YoungDepartment of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, PO74, King's College London, De Crespigny Park, London SE5 8AZ, UK.ORCID 0000-0003-2291-6952
Anthony J CleareDepartment of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, PO74, King's College London, De Crespigny Park, London SE5 8AZ, UK.ORCID 0000-0002-6990-939X
Stuart WatsonNorthern Centre for Mood Disorders, Translational and Clinical Research Institute, Newcastle University, Newcastle NE4 5PL, UK.ORCID 0000-0002-2558-3367

Funding

Efficacy and Mechanism Evaluation Programme 08/43/39Eli Lilly and Company n/a
6 · The paper itself

Abstract

backgroundOptimising treatments for patients with treatment-resistant depression (TRD) is key to reducing the burden of this severe illness. The anti-glucocorticoid medication metyrapone has mixed evidence supporting a role as a possible augmentation treatment in TRD. The degree of treatment resistance in depression has been associated prospectively and retrospectively with elevated inflammation, and inflammatory activity may influence responses to antidepressant treatments.

aimsTo investigate whether levels of pro-inflammatory cytokines are associated with clinical outcomes to metyrapone or placebo.

methodsA double-blind RCT randomised patients with TRD to 3 weeks of placebo or metyrapone augmentation to ongoing serotonergic antidepressants. No benefit of metyrapone was reported in the primary analysis. The current study assessed levels of pro-inflammatory proteins interleukin-6 (IL-6), tumour necrosis factor (TNFα), c-reactive protein (CRP) and interleukin-10 (IL-10) before randomisation and after treatment as potential moderators and/or mediators of clinical outcomes.

resultsThe three pro-inflammatory proteins (but not IL-10) were elevated in this sample of patients with TRD compared to a non-affected control group. High pre-treatment IL-6 levels predicted a poorer response in the trial overall but did not moderate response to metyrapone versus placebo. Changes in IL-6 indirectly mediated depression outcome, with metyrapone increasing IL-6 levels and IL-6 increase associated with a poorer outcome on depression. Other inflammatory proteins did not mediate or moderate treatment outcomes.

interpretationMetyrapone is hypothesised to have a therapeutic effect in depression on the basis of inhibiting the synthesis of cortisol. In this study, metyrapone did not reduce cortisol, possibly due to glucocorticoid system overcompensation). The mediation effect of IL-6 may support this and perhaps help to indicate why the treatment was not effective.

Indexed as

augmentationdepressionglucocorticoidinflammationmetyraponetreatment-resistance

Identifiers

PMID33669254
PMCPMC7920038

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Registered trials

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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.