Evidence map›Paper›PMID 38914860›Full record

Trial reportNature medicine2024

Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial.

Paul Glue, Colleen Loo, Johnson Fam, Hsien-Yuan Lane, Allan H Young, Peter Surman, BEDROC study investigators

Abstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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

30 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Safety and tolerance of oral ketamine: A systematic review.Psychiatry and clinical neurosciences · 2026
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  11. Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
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  14. Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations.Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater · 2026
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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

7 authors.

Paul GlueUniversity of Otago, Dunedin, New Zealand. Paul.glue@otago.ac.nz.ORCID 0000-0002-7305-2800
Colleen LooBlack Dog Institute & University of New South Wales, Sydney, New South Wales, Australia.
Johnson FamNational University of Singapore, Singapore, Singapore.
Hsien-Yuan LaneChina Medical University, Taichung, Taiwan.ORCID 0000-0003-2162-8174
Allan H YoungInstitute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Peter SurmanDouglas Pharmaceuticals, Auckland, New Zealand.
BEDROC study investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1-8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was -6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235 .

Indexed as

Delayed-Action PreparationsDepressive Disorder, Treatment-ResistantKetamineTabletsAdultAgedAntidepressive AgentsDouble-Blind MethodFemaleHumansMajor Depressive DisorderMaleMiddle AgedTreatment OutcomeAntidepressive AgentsDelayed-Action PreparationsKetamineTablets

Identifiers

PMID38914860
PMCPMC11271411

What OpenQuestion holds

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Registered trials

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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.