Evidence map›Paper›PMID 30894661›Full record

ReviewMolecular psychiatry2019

Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function.

Ronald S Duman, Ryota Shinohara, Manoela V Fogaça, Brendan Hare

Abstract readReview
In one paragraph

Review in Molecular psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
14.9field-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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

  1. Pooled it
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  11. Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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28 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

4 authors at 1 institution in 1 country.

Ronald S DumanDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. ronald.duman@yale.edu.
Ryota ShinoharaDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5279-2642
Manoela V FogaçaDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Brendan HareDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-6502-3188
Yale University · US

Funding

Role of mTOR and Synaptogenesis in the Actions of Rapid-Acting AntidepressantsR01MH093897 · NIMH · YALE UNIVERSITY · PI DILEONE, RALPH J · 2011 to 2021
$5.0M
Antidepressants: Signal Transduction and Gene ExpressionR37MH045481 · NIMH · YALE UNIVERSITY · PI DUMAN, RONALD S. · 2005 to 2014
$3.5M
Synaptic mechanisms underlying the rapid antidepressant actions of scopolamineR01MH105910 · NIMH · YALE UNIVERSITY · PI PICCIOTTO, MARINA R · 2014 to 2018
$2.2M
ANTIDEPRESSANTS AND SIGNAL TRANSDUCTION IN BRAINR01MH045481 · NIMH · YALE UNIVERSITY · PI DUMAN, RONALD S. · 1995 to 2004
$1.3M
NIMH NIH HHS R01 MH045481NIMH NIH HHS R01 MH093897NIMH NIH HHS R01 MH105910NIMH NIH HHS R37 MH045481
6 · The paper itself

Abstract

Efforts to develop efficacious antidepressant agents with novel mechanisms have been largely unsuccessful since the 1950's until the discovery of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist that produces rapid and sustained antidepressant actions even in treatment-resistant patients. This finding has ushered in a new era for the development of novel rapid-acting antidepressants that act at the NMDA receptor complex, but without dissociative and psychotomimetic side effects of ketamine. Here, we review the current state of rapid-acting antidepressant drug development, including NMDA channel blockers, glycine site agents, and allosteric modulators, as well as ketamine stereoisomers and metabolites. In addition, we focus on the neurobiological mechanisms underlying the actions of these diverse agents and discuss evidence of convergent mechanisms including increased brain-derived neurotrophic factor signaling, increased synthesis of synaptic proteins, and most notably increased GluR1 and synaptic connectivity in the medial prefrontal cortex. These convergent mechanisms provide insight for potential additional novel targets for drug development (e.g., agents that increase synaptic protein synthesis and plasticity). Importantly, the convergent effects on synapse formation and plasticity also reverse the well-documented neuronal and synaptic deficits associated with stress and depression, and thereby target the underlying pathophysiology of major depressive disorder.

Indexed as

AnimalsAntidepressive AgentsDepressionGlutamic AcidHumansKetamineMajor Depressive DisorderNeurobiologyNeurogenesisNeuronsReceptors, AMPAReceptors, N-Methyl-D-AspartateSignal TransductionSynapsesSynaptic TransmissionAntidepressive AgentsGlutamic AcidKetamineReceptors, AMPAReceptors, N-Methyl-D-Aspartate

Identifiers

PMID30894661
PMCPMC6754322
OpenAlexW2923276583

What Socratic 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 Socratic graph.