Evidence map›Paper›PMID 31290965›Full record

Trial reportThe international journal of neuropsychopharmacology2019

Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1).

Maggie Fedgchin, Madhukar Trivedi, Ella J Daly, Rama Melkote, Rosanne Lane, Pilar Lim, Dawn Vitagliano, Pierre Blier, Maurizio Fava, Michael Liebowitz and 8 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The international journal of neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02417064 (A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression), which is not on this map. Cited by 208 papers, 30 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
208citing papers in PubMed, 30 pooled it
63.0field-weighted citation impact, top 1% 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.

NCT02417064 phase3completednot on this map

A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression

TypeinterventionalSponsorJanssen Research & Development, LLCRan2015 to 2018Enrolled346ConditionsTreatment-resistant DepressionArmsEsketamine, Placebo, Duloxetine (Oral Antidepressant), Escitalopram (Oral antidepressant), Sertraline (Oral Antidepressant)
3 · Its place in the literature

Who cites it

208 citing papers in PubMed, 30 syntheses or guidelines pooled it, 575 citations in OpenAlex.

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  12. Quantitative evaluation of multiple treatment regimens for treatment-resistant depression.The international journal of neuropsychopharmacology · 2025
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148 more citing papers are in PubMed but not listed here.

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

18 authors at 9 institutions in 4 countries.

Maggie FedgchinJanssen Research and Development, Department of Neuroscience, Titusville, New Jersey.
Madhukar TrivediUniversity of Texas Southwestern Medical Center, Department of Psychiatry, Dallas, Texas.
Ella J DalyJanssen Research and Development, Department of Neuroscience, Titusville, New Jersey.
Rama MelkoteJanssen Research and Development, Clinical Biostatistics, Titusville, New Jersey.
Rosanne LaneJanssen Research and Development, Clinical Biostatistics, Titusville, New Jersey.
Pilar LimJanssen Research and Development, Clinical Biostatistics, Titusville, New Jersey.
Dawn VitaglianoJanssen Research and Development, Department of Neuroscience, Titusville, New Jersey.
Pierre BlierUniversity of Ottawa, Departments of Psychiatry and Cellular & Molecular Medicine, Ottawa, Ontario, Canada.
Maurizio FavaClinical Trials Network and Institute, Massachusetts General Hospital, Boston, Massachusetts.
Michael LiebowitzThe Medical Research Network, LLC, New York, New York.
Arun RavindranInstitute of Medical Sciences, University of Toronto, Department of Psychiatry, Toronto, Ontario, Canada.
Raphael GaillardCentre Hospitalier Sainte Anne, Service Hospitalo-Universitaire, Paris, France.
Hans Van Den AmeeleAZ Sint-Jan Brugge-Oostende, Department of Psychiatry, Brugge, Belgium.
Sheldon PreskornUniversity of Kansas School of Medicine-Wichita, Wichita, Kansas.
Husseini ManjiJanssen Research and Development, Department of Neuroscience, Titusville, New Jersey.
David HoughJanssen Research and Development, Department of Neuroscience, Titusville, New Jersey.
Wayne C DrevetsJanssen Research and Development, Department of Neuroscience, San Diego, California.
Jaskaran B SinghJanssen Research and Development, Department of Neuroscience, San Diego, California.
Janssen (United States) · USAZ Sint-Jan · BECentre Hospitalier Sainte-Anne · FRMassachusetts General Hospital · USMedical Research Network · USThe University of Texas Southwestern Medical Center · USUniversity of Ottawa · CAUniversity of Toronto · CAWichita State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAbout one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression.

methodsThis Phase 3, double-blind, multicenter study enrolled adults with moderate-to-severe depression and nonresponse to ≥2 antidepressants in the current depression episode. Eligible patients (N = 346) were randomized (1:1:1) to twice-weekly nasal spray treatment (esketamine [56 or 84 mg] or placebo) plus a newly initiated, open-label, oral antidepressant taken daily for 4 weeks. The primary efficacy endpoint was change from baseline to day 28 in the Montgomery-Asberg Depression Rating Scale total score, performed by blinded, remote raters. Based on the predefined statistical testing sequence, esketamine 84 mg/antidepressant had to be significant for esketamine 56 mg/antidepressant to be formally tested.

resultsStatistical significance was not achieved with esketamine 84 mg/antidepressant compared with antidepressant/placebo (least squares [LS] means difference [95% CI]: -3.2 [-6.88, 0.45]; 2-sided P value = .088). Although esketamine 56 mg/antidepressant could not be formally tested, the LS means difference was -4.1 [-7.67, -0.49] (nominal 2-sided P value = .027). The most common (>20%) adverse events reported for esketamine/antidepressant were nausea, dissociation, dizziness, vertigo, and headache.

conclusionsStatistical significance was not achieved for the primary endpoint; nevertheless, the treatment effect (Montgomery-Asberg Depression Rating Scale) for both esketamine/antidepressant groups exceeded what has been considered clinically meaningful for approved antidepressants vs placebo. Safety was similar between esketamine/antidepressant groups and no new dose-related safety concerns were identified. This study provides supportive evidence for the safety and efficacy of esketamine nasal spray as a new, rapid-acting antidepressant for patients with treatment-resistant depression.

trial registrationClinicalTrials.gov identifier: NCT02417064.

Indexed as

Administration, IntranasalAdministration, OralAdolescentAdultAntidepressive AgentsCitalopramDelayed-Action PreparationsDepressive Disorder, Treatment-ResistantDouble-Blind MethodDrug Therapy, CombinationDuloxetine HydrochlorideFemaleHumansKetamineMaleMiddle AgedAntidepressive AgentsCitalopramDelayed-Action PreparationsDuloxetine HydrochlorideEsketamineKetamineSertralineVenlafaxine Hydrochlorideesketamineketamines-ketaminetreatment-resistant depression

Identifiers

PMID31290965
PMCPMC6822141
OpenAlexW2961020354

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.