Evidence map›Paper›PMID 35994774›Full record

ArticleThe international journal of neuropsychopharmacology2022

A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine.

Bartholt Bloomfield-Clagett, Elizabeth D Ballard, Deanna K Greenstein, Samuel T Wilkinson, Michael F Grunebaum, James W Murrough, Sanjay J Mathew, Jennifer L Phillips, Maurizio Fava, Gerard Sanacora and 1 more

Open access · goldAbstract read
In one paragraph

Article in The international journal of neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. A pilot randomized controlled trial of ketamine in Borderline Personality Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Trial
  3. Psychedelic therapeutics in psychiatric conditions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  4. Article
  5. Ketamine in neuropsychiatric disorders: an update.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    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

11 authors at 7 institutions in 2 countries.

Bartholt Bloomfield-ClagettExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Elizabeth D BallardExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Deanna K GreensteinExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Samuel T WilkinsonDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Michael F GrunebaumDepartment of Psychiatry, Columbia University Medical Center and New York State Psychiatric Institute, New York, USA.
James W MurroughDepression and Anxiety Center for Discovery and Treatment, Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sanjay J MathewMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-2715-6641
Jennifer L PhillipsUniversity of Ottawa Institute of Mental Health Research and Department of Psychiatry, Ottawa, ON, Canada.
Maurizio FavaDepartment of Psychiatry, Massachusetts General Hospital, Boston, USA.
Gerard SanacoraDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0003-3722-8829
Carlos A ZarateExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USYale University · USBaylor College of Medicine · USBoston University · USCenter for Discovery · USColumbia University Irving Medical Center · USUniversity of Ottawa · CA

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Glutamatergic Modulators for Rapid & Sustained Antidepressant EffectZIAMH002857 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2009 to 2025
$55.0M
Intramural NIH HHS ZIA MH002857NCATS NIH HHS UL1 TR001863NIH HHS ZIAMH002857
6 · The paper itself

Abstract

backgroundClinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine's specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings.

methodsData for this participant-level integrative data analysis were drawn from 151 participants across 10 studies, and linear regression was used to examine the relationship between placebo response for suicidal ideation vs other depressive symptoms indexed from standard rating scales-specifically, depressed mood, anhedonia, anxiety, and guilt-over time.

resultsFor participants receiving saline placebo (n = 46), greater placebo response was observed for suicidal ideation compared with other symptoms indexed from standard depression rating scales, except for anxiety. For those receiving midazolam placebo (n = 105), greater placebo response was observed for suicidal ideation compared with depressed mood or anhedonia, and no significant differences were observed when comparing suicidal ideation with anxiety or guilt.

conclusionsTaken together, the results provide preliminary evidence of a differential placebo response for suicidal ideation vs other depressive symptoms, while anxiety and suicidal ideation appear to produce similar placebo response profiles. These findings may help explain the more modest findings in clinical IV ketamine trials for suicidal ideation than overall depression.

Indexed as

KetamineMajor Depressive DisorderAnhedoniaData AnalysisDepressionHumansMidazolamPlacebo EffectPsychiatric Status Rating ScalesSuicidal IdeationKetamineMidazolamclinical trialsketaminemidazolamplaceboSuicidal ideation

Identifiers

PMID35994774
PMCPMC9593215
OpenAlexW4292664328

What OpenQuestion holds

Textmetadata
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.