Evidence map›Paper›PMID 37568215›Full record

ArticleTrials2023

The effects of esketamine and treatment expectation in acute major depressive disorder (Expect): study protocol for a pharmacological fMRI study using a balanced placebo design.

Irina Falkenberg, Florian Bitsch, Wei Liu, Alexandros Matsingos, Laila Noor, Christoph Vogelbacher, Cüneyt Yildiz, Tilo Kircher

Open access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% 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

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. 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

8 authors at 1 institution in 1 country.

Irina FalkenbergDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany. Irina.falkenberg@med.uni-marburg.de.ORCID http://orcid.org/0000-0003-3699-0803
Florian BitschDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Wei LiuDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Alexandros MatsingosDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Laila NoorDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Christoph VogelbacherDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Cüneyt YildizDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Tilo KircherDepartment of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.
Philipps University of Marburg · DE

Funding

Deutsche Forschungsgemeinschaft 422744262
6 · The paper itself

Abstract

backgroundMajor depressive disorder (MDD) is a highly prevalent (8-15%), severely disabling disorder and is associated with enormous socioeconomic impact. Antidepressant medication for the treatment of MDD has proven effective in RCTs; however, placebo response is also substantial. Given the potential benefits of modulating the placebo response in patient care and pharmacological research, understanding the mechanisms underlying placebo response is of high clinical relevance. The placebo response is mediated by treatment expectation, i.e. an individual's belief about whether and how much they will improve as a consequence of their treatment. The mechanisms and moderators of treatment expectation effects in MDD are poorly understood. Initial brain imaging studies on placebo responses in MDD point towards the relevance of the lateral prefrontal cortex and the rostral anterior cingulate cortex (rACC). In this project, we will investigate the neural mechanisms underlying the antidepressant effects of treatment expectation associated with the fast-acting antidepressant esketamine in patients with MDD. Esketamine is an NMDA receptor antagonist inducing antidepressant effects within hours.

methodsWe will employ a fully balanced placebo design with the factors "treatment" (i.v. esketamine / placebo) and verbally induced "expectation" (high / low) combined with fMRI (resting state, emotion and reward processing paradigms) to investigate the psychological and neural mechanisms underlying the antidepressant effects of expectation, and how these interact with the pharmacological effects of esketamine. DISCUSSION: The insights gained by this project promise fundamental implications for clinical treatment and future drug trials. Unraveling the mechanisms underlying expectation effects on antidepressant treatment may inform (1) strategies to modulate these effects and thus improve assay sensitivity in RCTs and (2) novel treatment regiments aiming to maximize the synergistic effects of expectation and pharmacological treatment in the clinical care of patients with MDD.

trial registrationThis trial has been prospectively registered with the EU Clinical Trials Register: EudraCT-No.: 2020-000784-23 (November 17, 2020).

Indexed as

Antidepressive AgentsKetamineMajor Depressive DisorderHumansMagnetic Resonance ImagingTreatment OutcomeAntidepressive AgentsEsketamineKetamineEsketamineExpectationfMRIMajor depressionPlacebo

Identifiers

PMID37568215
PMCPMC10416369
OpenAlexW4385764092

What OpenQuestion holds

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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.