Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 4 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 4 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Effectiveness of pharmacological and non-pharmacological interventions for treatment-resistant depression in older patients: a systematic review and meta-analysis.BMJ mental health · 2025Pooled it
- Comparative safety and tolerability of ketamine and esketamine for major depressive disorder: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies.The lancet. Psychiatry · 2023Pooled it
- International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.Molecular psychiatry · 2022Pooled it
- High-order brain interactions during ketamine-induced state changes: A functional marker of response in late-life treatment-resistant depression?Translational psychiatry · 2026Trial
- A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.Journal of neurodevelopmental disorders · 2025Trial
- Comparison of the Antianhedonic Effects of Repeated-dose Intravenous Ketamine in Older and Younger Adults with Major Depressive Episode.Current neuropharmacology · 2025Trial
- Neural complexity EEG biomarkers of rapid and post-rapid ketamine effects in late-life treatment-resistant depression: a randomized control trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention.Molecular psychiatry · 2023Trial
- Ketamine or Esketamine in Special Populations of Patients With Treatment-Resistant Depression.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings.Molecular psychiatry · 2025Article
- Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.Translational psychiatry · 2024Article
- Ketamine in the effective management of chronic pain, depression, and posttraumatic stress disorder for Veterans: A meta-analysis and systematic review.Frontiers in psychiatry · 2024Review
- Ketamine for the treatment of major depression: a systematic review and meta-analysis.EClinicalMedicine · 2023Article
- Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic.Frontiers in psychiatry · 2023Review
- A comparative study of amplitude of low-frequence fluctuation of resting-state fMRI between the younger and older treatment-resistant depression in adults.Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and effects on cortical excitation/inhibition (E/I) ratio using resting electroencephalography gamma and alpha power, were also determined. Thirty-three medication-free US military veterans (mean age 62; range: 55-72; 10 female) with LL-TRD were randomized double-blind. The trial was terminated when dose superiority was established. All interventions were safe and well-tolerated. Pre-specified decision rules terminated KET 0.1 (N = 4) and KET 0.25 (N = 5) for inferiority. Posterior probability was 0.89 that day-seven treatment response was superior for KET 0.5 (N = 11; response rate = 70%) compared to MID (N = 13; response rate = 46%). Persistent treatment response at day 28 was superior for KET 0.5 (response rate = 82%) compared to MID (response rate = 37%). KET 0.5 had high posterior probability of increased frontal gamma power (posterior probability = 0.99) and decreased posterior alpha power (0.89) during infusion, suggesting an acute increase in E/I ratio. These results suggest that 0.5 mg/kg is an effective initial IV ketamine dose in LL-TRD, although further studies in individuals older than 75 are required.
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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.