ArticleThe international journal of neuropsychopharmacology2022
Relationship Between Dissociation and Antidepressant Effects of Esketamine Nasal Spray in Patients With Treatment-Resistant Depression.
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. It is linked to 3 registered trials, which are not on this map. Cited by 38 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
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
A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression
A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression
Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Pooled it
- Ketamine-induced altered states of consciousness: a systematic review of implications for therapeutic outcomes in psychiatric practices.European archives of psychiatry and clinical neuroscience · 2025Pooled it
- Esketamine and Psilocybin-The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review.International journal of molecular sciences · 2022Pooled it
- A Randomised Controlled Trial on the Efficacy of Ketamine versus Electroconvulsive Therapy in Severe Depression with Suicidal Ideation.Neuropsychobiology · 2026Trial
- Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine or esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial.Trends in psychiatry and psychotherapy · 2025Trial
- Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial.BMJ (Clinical research ed.) · 2024Trial
- Adverse Events and Measurement of Dissociation After the First Dose of Esketamine in Patients With TRD.The international journal of neuropsychopharmacology · 2023Trial
- Is (S)-norketamine an active mediator of esketamine's antidepressant effects?Molecular psychiatry · 2026Article
- Lamotrigine is not associated with differential clinical outcomes in a real-world sample of patients with unipolar depression receiving ketamine or esketamine.Psychopharmacology · 2026Article
- Esketamine Nasal Spray: Mechanism of Action, Clinical, and Translational Science.Clinical and translational science · 2026Review
- Integrating Psychiatric, Psychotherapeutic, and Nursing Care in Intranasal Esketamine for Treatment-Resistant Depression.Journal of clinical medicine · 2026Review
- Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study.Brain sciences · 2026Article
- Patients' Voices on Ketamine for Treatment-Resistant Depression: A Narrative Review of Qualitative Perspectives.Journal of clinical medicine · 2025Review
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025Review
- Esketamine use in real-world clinical practice in patients with treatment-resistant depression.European psychiatry : the journal of the Association of European Psychiatrists · 2025Article
- Deconstructing the trip treatment: are hallucinogenic effects critical to the therapeutic benefits of psychedelics?NPP - digital psychiatry and neuroscience · 2025Review
- Are "mystical experiences" essential for antidepressant actions of ketamine and the classic psychedelics?European archives of psychiatry and clinical neuroscience · 2025Review
- The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment.International journal of molecular sciences · 2025Article
- Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways.Science advances · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn this post-hoc analysis, data from 2 positive, pivotal, phase 3 trials of esketamine nasal spray (ESK) in treatment-resistant depression (TRD)-short-term study (TRANSFORM-2) and maintenance study (SUSTAIN-1)-were analyzed to evaluate the relationship between dissociation and antidepressant effects of ESK.
methodsAnalysis by responder status, correlation analysis, and mediation analysis were performed to assess the relationships between peak Clinician Administered Dissociative States Scale (CADSS) scores after first (day 1) and last (day 25) ESK dose and change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at the first (day 2) and last assessments (day 28) in TRANSFORM-2 and peak CADSS after first maintenance ESK dose and time to relapse in SUSTAIN-1 (only for mediation analysis).
resultsIn TRANSFORM-2, the percentage of responders (>50% reduction in MADRS) at day 2 and day 28 did not significantly differ between patients who did vs did not manifest significant dissociation (peak CADSS scores >4 or ≤4, respectively) following the first ESK dose. Spearman correlation coefficients between dissociation and depression improvement were nonsignificant and close to zero. CADSS scores did not significantly mediate the reduction in MADRS at day 2 or 28 in TRANSFORM-2 or the time to depression relapse in SUSTAIN-1. The mean difference in MADRS between ESK and active-control arms persisted beyond day 2 without significant change across time, although the mean peak CADSS scores significantly decreased across consecutive doses and fewer patients experienced significant dissociation after the last ESK dose compared with the first.
conclusionWithin the dose range tested, the dissociative and antidepressant effects of ESK were not significantly correlated.
trial registrationNCT02417064 (TRANSFORM-1); NCT02418585(TRANSFORM-2); NCT02493868 (SUSTAIN-1).
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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.