Evidence map›Paper›PMID 30153752›Full record

Trial reportThe American journal of psychiatry2018

Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.

Nolan R Williams, Boris D Heifets, Christine Blasey, Keith Sudheimer, Jaspreet Pannu, Heather Pankow, Jessica Hawkins, Justin Birnbaum, David M Lyons, Carolyn I Rodriguez and 1 more

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The American journal of psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed, 11 pooled it
38.7field-weighted citation impact, top 1% of its field
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

228 citing papers in PubMed, 11 syntheses or guidelines pooled it, 486 citations in OpenAlex.

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  2. Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?European psychiatry : the journal of the Association of European Psychiatrists · 2026
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168 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Nolan R WilliamsFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Boris D HeifetsFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Christine BlaseyFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Keith SudheimerFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Jaspreet PannuFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Heather PankowFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Jessica HawkinsFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Justin BirnbaumFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
David M LyonsFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Carolyn I RodriguezFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
Alan F SchatzbergFrom the Department of Psychiatry and Behavioral Sciences and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, Calif.; the Department of Psychology, Palo Alto University, Palo Alto, Calif.; and the VA Palo Alto Health Care System, Palo Alto, Calif.
VA Palo Alto Health Care System · US

Funding

Spectrum Stanford Center for clinical and Translational Research and EducationUL1TR001085 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$37.1M
NCATS NIH HHS UL1 TR001085
6 · The paper itself

Abstract

objectiveIn addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects.

methodIn a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1.

resultsIn the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis.

conclusionsThe findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.

Indexed as

AdultAntidepressive AgentsCross-Over StudiesDepressive Disorder, Treatment-ResistantDouble-Blind MethodDrug Administration ScheduleFemaleHumansKetamineMaleNaltrexoneNarcotic AntagonistsPsychiatric Status Rating ScalesAntidepressive AgentsKetamineNaltrexoneNarcotic AntagonistsDepressionKetamineOpioid

Identifiers

PMID30153752
PMCPMC6395554
OpenAlexW2889166554

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.