Evidence map›Paper›PMID 31215725›Full record

ReviewPsychiatry and clinical neurosciences2019

Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective.

Kenji Hashimoto

Registry-linked trialOpen access · hybridAbstract readHistorical ArticleReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Psychiatry and clinical neurosciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04399070 (Effect of S-ketamine on Depressed Patients Undergoing Electroconvulsive Therapy-a Randomized, Double-blind, Controlled Clinical Study), which is not on this map. Cited by 144 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 7 pooled it
32.4field-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.

NCT04399070 naunknown statusnot on this mapstarted 2020, after this paper: background citation

Effect of S-ketamine on Depressed Patients Undergoing Electroconvulsive Therapy-a Randomized, Double-blind, Controlled Clinical Study

TypeinterventionalSponsorYan QiuRan2020 to 2021Enrolled150ConditionsDepression, Bipolar, Depression, Unipolar, Major Depressive Disorder, Manic-Depressive - Now DepressedArmsS-ketamine, ketamine, saline
3 · Its place in the literature

Who cites it

144 citing papers in PubMed, 7 syntheses or guidelines pooled it, 318 citations in OpenAlex.

  1. Pooled it
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  11. Intravenous arketamine for treatment-resistant depression: open-label pilot study.European archives of psychiatry and clinical neuroscience · 2021
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  13. Article
  14. Review
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  17. Inflammation and treatment strategies for suicidal behavior.The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2026
    Review
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  20. Review

84 more citing papers are in PubMed but not listed here.

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

1 author at 1 institution in 1 country.

Kenji HashimotoDivision of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.ORCID https://orcid.org/0000-0002-8892-0439
Center for Forensic Mental Health, Chiba University · JP

Funding

AMED JP19dm0107119
6 · The paper itself

Abstract

Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one-third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists an unmet medical need for rapidly acting antidepressants with beneficial effects in treatment-resistant patients with MDD or BD. Accumulating evidence suggests that the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine produces rapid and sustained antidepressant effects in treatment-resistant patients with MDD or BD. Ketamine is a racemic mixture comprising equal parts of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine). Because (S)-ketamine has higher affinity for NMDAR than (R)-ketamine, esketamine was developed as an antidepressant. On 5 March 2019, esketamine nasal spray was approved by the US Food and Drug Administration. However, preclinical data suggest that (R)-ketamine exerts greater potency and longer-lasting antidepressant effects than (S)-ketamine in animal models of depression and that (R)-ketamine has less detrimental side-effects than (R,S)-ketamine or (S)-ketamine. In this article, the author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamine. Furthermore, the author discusses the other potential rapid-acting antidepressant candidates (i.e., NMDAR antagonists and modulators, low-voltage-sensitive T-type calcium channel inhibitor, potassium channel Kir4.1 inhibitor, negative modulators of γ-aminobutyric acid, and type A [GABA

Indexed as

AnimalsAntidepressive AgentsBipolar DisorderExcitatory Amino Acid AntagonistsHistory, 20th CenturyHistory, 21st CenturyHumansKetamineMajor Depressive DisorderReceptors, N-Methyl-D-AspartateAntidepressive AgentsEsketamineExcitatory Amino Acid AntagonistsKetaminenorketamineReceptors, N-Methyl-D-Aspartategut microbiota(R)-ketamine (or arketamine), (S)-ketamine (or esketamine), (S)-norketamine

Identifiers

PMID31215725
PMCPMC6851782
OpenAlexW2950701273

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.