Evidence map›Paper›PMID 41569403›Full record

Trial reportPharmacological reports : PR2026

A preliminary proof-of-concept trial on the effects of ketamine on fatigue: a randomized crossover trial.

Taichi Goto, Joy D Kreskow, Alexander L R Ross, Catherine L Blumhorst, Justin J Zhao, Andrew J Mannes, Miroslav Bačkonja, Carlos A Zarate, Leorey N Saligan

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Pharmacological reports : PR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Taichi GotoNational Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.ORCID http://orcid.org/0000-0001-7140-8175
Joy D KreskowNational Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.
Alexander L R RossNational Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.ORCID http://orcid.org/0000-0001-6107-1927
Catherine L BlumhorstNational Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.ORCID http://orcid.org/0009-0003-7746-6351
Justin J ZhaoNational Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.ORCID http://orcid.org/0009-0002-8626-2089
Andrew J MannesDepartment of Perioperative Medicine, NIH Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.ORCID http://orcid.org/0000-0001-5834-5667
Miroslav BačkonjaNational Center for Complementary and Integrative Health, NIH, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.
Carlos A ZarateExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.ORCID http://orcid.org/0000-0003-4442-7412
Leorey N SaliganNational Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA. ls1684@sn.rutgers.edu.ORCID http://orcid.org/0000-0001-9481-7836

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFatigue, a prevalent symptom of chronic illness, impacts quality of life. This proof-of-concept, randomized, double-blind, crossover trial assessed the anti-fatigue effects of ketamine (0.5 mg/kg) versus midazolam (0.045 mg/kg), the active comparator.

methodsTen participants, who were cancer survivors, with fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome, or systemic lupus erythematosus, were randomized into Arm 1 (n = 4, Period 1: ketamine to Period 2: midazolam) or Arm 2 (n = 6, Period 1: midazolam to Period 2: ketamine).

resultsThe two periods were separately analyzed because of carryover effects with baseline fatigue scores, assessed by the fatigue visual analog scale (VAS), between the study periods (p = 0.03). Looking at changes in fatigue VAS scores from baseline (pre-infusion) to 3 days post-infusion, the ketamine group had a 21.0% decrease in Period 1 and 10.9% in Period 2, while the midazolam group showed a 17.7% decrease in Period 1 and 12.6% in Period 2. We did not observe a statistically significant difference in both periods. The largest fatigue score reduction for the ketamine group was at 1 day post-infusion, at - 38.7% in Period 1.

conclusionDespite no statistical significance, a reduction in real-time fatigue scores was observed, which exceeded the 20% efficacy threshold, the primary outcome, in the ketamine arm from pre-infusion to 3 days post-infusion. The carryover effects and the peak reduction in fatigue at 24 hours after ketamine administration suggest that future trials may need to consider a study design without cross-over and an optimal active placebo alternative.

Indexed as

FatigueKetamineAdultCross-Over StudiesDouble-Blind MethodFemaleHumansMaleMidazolamMiddle AgedProof of Concept StudyQuality of LifeKetamineMidazolamActive placeboChronic illnessGlutamate receptorMidazolamPilot study

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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.