ArticleNature. Mental health2023
Randomized trial of ketamine masked by surgical anesthesia in patients with depression.
Article in Nature. Mental health, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 57 papers, 4 of them syntheses that pooled 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.
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.
Double-blind Trial of Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery
A Phase 2 Randomized Study Examining the Safety, Feasibility, and Effectiveness of Masking Psilocybin Therapy With General Anesthesia in Major Depressive Disorder
Who cites it
57 citing papers in PubMed, 4 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Effectiveness of ketamine-assisted psychotherapy as a treatment for treatment-resistant depression: a systematic review.Psychopharmacology · 2026Pooled it
- Psychedelics as an intervention for psychological, existential distress in terminally ill patients: A systematic review and network meta-analysis.Journal of psychopharmacology (Oxford, England) · 2026Pooled it
- Psychedelic-Assisted Therapies for Psychosocial Symptoms in Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2025Pooled it
- Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis.Frontiers in psychiatry · 2024Pooled it
- Esketamine hydrochloride in the management of moderate-to-severe depressive symptoms in patients undergoing multiple wound repair surgeries: A multi-centre randomized, double-blind, placebo-controlled trial.Clinical and translational medicine · 2026Trial
- Safety and Efficacy of the NMDA-2b-Selective Negative Allosteric Modulator BI 1569912: A Phase Ib Randomized Trial in Major Depressive Disorder.Clinical pharmacology and therapeutics · 2025Trial
- Ketamine's impact on mood after day-case surgery and its relation to obesity: a randomised controlled trial in women undergoing fractional curettage.BMC women's health · 2025Trial
- Opioids diminish the placebo antidepressant response: Observational post hoc findings from a randomized controlled ketamine trial.Journal of affective disorders · 2025Trial
- Optimizing esketamine administration for postoperative depression: a comprehensive study on laparoscopic bariatric surgery patients.Psychopharmacology · 2025Trial
- Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.Psychiatry and clinical neurosciences · 2024Trial
- Is (S)-norketamine an active mediator of esketamine's antidepressant effects?Molecular psychiatry · 2026Article
- The Emerging Neurobiology of Psychedelics: Critical Periods, Metaplasticity, and Extracellular Matrix Remodeling.Annual review of neuroscience · 2026Review
- Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care.Translational psychiatry · 2026Review
- Measuring and appraising placebo effects in clinical trials: contemporary challenges and approaches in psychiatry.The lancet. Psychiatry · 2026Review
- Challenges with clinical trial participants in studies with classical psychedelics: A position statement from the National Network of Depression Centers' task group on psychedelics and related compounds.Journal of psychopharmacology (Oxford, England) · 2026Article
- The science of psychedelic medicine.Nature medicine · 2026Review
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Causal Inference in Studies with Functional Unmasking: Psychedelics and Beyond.medRxiv : the preprint server for health sciences · 2026Article
- Treating addiction with an addictive drug: the ketamine paradox revisited.Frontiers in psychiatry · 2026Review
- Generalizable structure-function covariation predictive of antidepressant response revealed by target-oriented multimodal fusion.Nature. Mental health · 2026Article
Corrections and comments
- Update of
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. We present a single-center, parallel-arm, triple-masked, randomized, placebo-controlled trial assessing the antidepressant efficacy of intravenous ketamine masked by surgical anesthesia (ClinicalTrials.gov, NCT03861988). Forty adult patients with major depressive disorder who were scheduled for routine surgery were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during usual anesthesia. All participants, investigators, and direct patient care staff were masked to treatment allocation. The primary outcome was depression severity measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1, 2, and 3 days post-infusion. After all follow-up visits, participants were asked to guess which intervention they received. A mixed-effects model showed no evidence of effect of treatment assignment on the primary outcome (-5.82, 95% CI -13.3 to 1.64, p=0.13). 36.8% of participants guessed their treatment assignment correctly; both groups allocated their guesses in similar proportions. In conclusion, a single dose of intravenous ketamine delivered during surgical anesthesia had no greater effect than placebo in acutely reducing the severity of depressive symptoms in adults with major depressive disorder. This trial successfully masked treatment allocation in moderate-to-severely depressed patients using surgical anesthesia. Although this masking strategy is impractical for most placebo-controlled trials, future studies of novel antidepressants with acute psychoactive effects should make efforts to fully mask treatment assignment in order to minimize subject-expectancy bias.
Identifiers
What OpenQuestion holds
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.