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Placebo effects in mental health disorders: protocol for an umbrella review

Placebo effects in mental health disorders: protocol for an umbrella review
Placebo effects in mental health disorders: protocol for an umbrella review

Introduction: given the high prevalence of mental health disorders and their significant socioeconomic burden, there is a need to develop improved treatments, and to evaluate them through placebo-controlled trials. However, the magnitude of the placebo response in randomised controlled trials to test medications may be substantial, affecting their interpretation. Therefore, improved understanding of the patient, trial and mental disorder factors that influence placebo responses would inform clinical trial design to better detect active treatment effects. There is a growing literature exploring the placebo response within specific mental health disorders, but no overarching synthesis of this research has been produced to date. We present a protocol for an umbrella review of systematic reviews and/or meta-analyses in which we aim to understand the effect size and potential predictors of placebo response within, and across, mental health disorders.

Methods and analysis: we will systematically search databases (Medline, PsycINFO, EMBASE+EMBASE Classic, Web of Knowledge) for systematic reviews and/or meta-analyses that report placebo effect size in clinical trials in patients with mental health disorders (initial search date 23 October 2022). Screening of abstracts and full texts will be done in pairs. We will extract data to qualitatively examine how placebo effect size varies across mental health disorders. We also plan to qualitatively summarise predictors of increased placebo response identified either quantitatively (eg, through meta-regression) or qualitatively. Risk of bias will be assessed using the AMSTAR-2 tool. We aim to not only summarise the current literature but also to identify gaps in knowledge and generate further hypotheses.

Ethics and dissemination: we do not believe there are any specific ethical considerations relevant to this study. We will publish the results in a peer-reviewed journal.

Humans, Mental Disorders/drug therapy, Mental Health, Placebo Effect, Systematic Reviews as Topic
2044-6055
Huneke, Nathan T.M.
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Amin, Jay
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Baldwin, David S.
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Chamberlain, Samuel R.
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Correll, Christoph U.
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Garner, Matthew
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Hill, Catherine M.
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Hou, Ruihua
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Howes, Oliver D.
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Sinclair, Julia M.A.
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Solmi, Marco
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Cortese, Samuele
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Huneke, Nathan T.M.
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Amin, Jay
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Baldwin, David S.
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Chamberlain, Samuel R.
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Correll, Christoph U.
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Garner, Matthew
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Hill, Catherine M.
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Hou, Ruihua
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Howes, Oliver D.
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Sinclair, Julia M.A.
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Solmi, Marco
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Cortese, Samuele
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Huneke, Nathan T.M., Amin, Jay, Baldwin, David S., Chamberlain, Samuel R., Correll, Christoph U., Garner, Matthew, Hill, Catherine M., Hou, Ruihua, Howes, Oliver D., Sinclair, Julia M.A., Solmi, Marco and Cortese, Samuele (2023) Placebo effects in mental health disorders: protocol for an umbrella review. BMJ Open, 13 (11), [e073946]. (doi:10.1136/bmjopen-2023-073946).

Record type: Article

Abstract

Introduction: given the high prevalence of mental health disorders and their significant socioeconomic burden, there is a need to develop improved treatments, and to evaluate them through placebo-controlled trials. However, the magnitude of the placebo response in randomised controlled trials to test medications may be substantial, affecting their interpretation. Therefore, improved understanding of the patient, trial and mental disorder factors that influence placebo responses would inform clinical trial design to better detect active treatment effects. There is a growing literature exploring the placebo response within specific mental health disorders, but no overarching synthesis of this research has been produced to date. We present a protocol for an umbrella review of systematic reviews and/or meta-analyses in which we aim to understand the effect size and potential predictors of placebo response within, and across, mental health disorders.

Methods and analysis: we will systematically search databases (Medline, PsycINFO, EMBASE+EMBASE Classic, Web of Knowledge) for systematic reviews and/or meta-analyses that report placebo effect size in clinical trials in patients with mental health disorders (initial search date 23 October 2022). Screening of abstracts and full texts will be done in pairs. We will extract data to qualitatively examine how placebo effect size varies across mental health disorders. We also plan to qualitatively summarise predictors of increased placebo response identified either quantitatively (eg, through meta-regression) or qualitatively. Risk of bias will be assessed using the AMSTAR-2 tool. We aim to not only summarise the current literature but also to identify gaps in knowledge and generate further hypotheses.

Ethics and dissemination: we do not believe there are any specific ethical considerations relevant to this study. We will publish the results in a peer-reviewed journal.

Text
e073946.full - Version of Record
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Accepted/In Press date: 6 November 2023
e-pub ahead of print date: 30 November 2023
Published date: 30 November 2023
Additional Information: Funding Information: Competing interests DSB is President of the British Association for Psychopharmacology (BAP) and Editor of Human Psychopharmacology journal (for which he receives an Editor’s honorarium). CMH has acted on an expert advisory board for Neurim pharmaceuticals. ODH is a part-time employee and stock holder of Lundbeck A/s. He has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Neurocrine, Otsuka, Sunovion, Recordati, Roche and Viatris/ Mylan. ODH has a patent for the use of dopaminergic imaging. All other authors declare no competing interests. MS has received honoraria/has been a consultant for Angelini, Lundbeck, Otsuka. SRC receives an honorarium from Elsevier for associate editor work at two academic journals. SCo has received honoraria from non-profit associations (BAP, ACAMH, CADDRA) for educational activities. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, Vertex and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax and Quantic. Publisher Copyright: © Author(s) (or their employer(s)) 2023.
Keywords: Humans, Mental Disorders/drug therapy, Mental Health, Placebo Effect, Systematic Reviews as Topic

Identifiers

Local EPrints ID: 485841
URI: http://eprints.soton.ac.uk/id/eprint/485841
ISSN: 2044-6055
PURE UUID: 43519f30-824c-4c8c-9bbc-480b6a76fd22
ORCID for Nathan T.M. Huneke: ORCID iD orcid.org/0000-0001-5981-6707
ORCID for Jay Amin: ORCID iD orcid.org/0000-0003-3792-0428
ORCID for David S. Baldwin: ORCID iD orcid.org/0000-0003-3343-0907
ORCID for Samuel R. Chamberlain: ORCID iD orcid.org/0000-0001-7014-8121
ORCID for Matthew Garner: ORCID iD orcid.org/0000-0001-9481-2226
ORCID for Ruihua Hou: ORCID iD orcid.org/0000-0001-6127-1478
ORCID for Julia M.A. Sinclair: ORCID iD orcid.org/0000-0002-1905-2025
ORCID for Samuele Cortese: ORCID iD orcid.org/0000-0001-5877-8075

Catalogue record

Date deposited: 20 Dec 2023 17:38
Last modified: 12 Nov 2024 03:05

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Contributors

Author: Nathan T.M. Huneke ORCID iD
Author: Jay Amin ORCID iD
Author: Samuel R. Chamberlain ORCID iD
Author: Christoph U. Correll
Author: Matthew Garner ORCID iD
Author: Catherine M. Hill
Author: Ruihua Hou ORCID iD
Author: Oliver D. Howes
Author: Marco Solmi
Author: Samuele Cortese ORCID iD

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