ReviewExperimental and clinical psychopharmacology2015
A brief history of the development of antidepressant drugs: from monoamines to glutamate.
Review in Experimental and clinical psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04234776 (Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression), which is not on this map. Cited by 204 papers, 11 of them syntheses that pooled 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.
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.
Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression
Who cites it
204 citing papers in PubMed, 11 syntheses or guidelines pooled it, 576 citations in OpenAlex.
- Effectiveness of interventions for anxiety and depression in children and young people: an umbrella review of meta-analyses.European child & adolescent psychiatry · 2026Pooled it
- Beyond Depression: The Role of Antidepressants in Managing Chronic Temporomandibular Disorders. A Systematic Review.Journal of oral rehabilitation · 2025Pooled it
- Predicting the treatment outcomes of major depressive disorder interventions with baseline resting-state functional connectivity: a meta-analysis.BMC psychiatry · 2025Pooled it
- Pooled it
- Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.Molecular psychiatry · 2025Pooled it
- Fears Worth Testing Out: A Systematic Review of the Neural Mechanisms of Treatment Outcome for Anxiety-Related Disorders.Current topics in behavioral neurosciences · 2025Pooled it
- Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review.The international journal of neuropsychopharmacology · 2024Pooled it
- Associations of Antidepressants With Atrial Fibrillation and Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Depression and obesity among females, are sex specificities considered?Archives of women's mental health · 2021Pooled it
- Antidepressants and Risk of Sudden Cardiac Death: A Network Meta-Analysis and Systematic Review.Medical sciences (Basel, Switzerland) · 2021Pooled it
- A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants.Drug safety · 2021Pooled it
- A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers.Clinical pharmacology and therapeutics · 2024Trial
- Subanesthetic Ketamine Suppresses Locus Coeruleus-Mediated Alertness Effects: A 7T fMRI Study.The international journal of neuropsychopharmacology · 2024Trial
- Individualized fMRI connectivity defines signatures of antidepressant and placebo responses in major depression.Molecular psychiatry · 2023Trial
- Spatio-temporal dynamics of EEG features during sleep in major depressive disorder after treatment with escitalopram: a pilot study.BMC psychiatry · 2020Trial
- Randomized, double-blind, placebo-controlled study to assess the efficacy and safety of vortioxetine in Japanese patients with major depressive disorder.Psychiatry and clinical neurosciences · 2020Trial
- Bioequivalence Study of Amitriptyline Hydrochloride Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.Drug design, development and therapy · 2020Trial
- Bioequivalence Study Of A Fixed-Dose Combination Tablet Containing Melitracen 10 mg And Flupentixol 0.5 mg In Healthy Chinese Volunteers Under Fasted And Fed Conditions.Drug design, development and therapy · 2019Trial
- Treating major depression with yoga: A prospective, randomized, controlled pilot trial.PloS one · 2017Trial
- From depression to bone health: examining the skeletal effects of classical and rapid-acting antidepressants.The international journal of neuropsychopharmacology · 2026Review
144 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Major depressive disorder (MDD) is a chronic, recurring, and debilitating mental illness that is the most common mood disorder in the United States. It has been almost 50 years since the monoamine hypothesis of depression was articulated, and just over 50 years since the first pharmacological treatment for MDD was discovered. Several monoamine-based pharmacological drug classes have been developed and approved for the treatment of MDD; however, remission rates are low (often less than 60%) and there is a delayed onset before remission of depressive symptoms is achieved. As a result of a "proof-of-concept" study in 2000 with the noncompetitive NMDA antagonist ketamine, a number of studies have examined the glutamatergic systems as viable targets for the treatment of MDD. This review will provide a brief history on the development of clinically available antidepressant drugs, and then review the possible role of glutamatergic systems in the pathophysiology of MDD. Specifically, the glutamatergic review will focus on the N-methyl-D-aspartate (NMDA) receptor and the efficacy of drugs that target the NMDA receptor for the treatment of MDD. The noncompetitive NMDA receptor antagonist ketamine, which has consistently produced rapid and sustained antidepressant effects in MDD patients in a number of clinical studies, has shown the most promise as a novel glutamatergic-based treatment for MDD. However, compounds that target other glutamatergic mechanisms, such as GLYX-13 (a glycine-site partial agonist at NMDA receptors) appear promising in early clinical trials. Thus, the clinical findings to date are encouraging and support the continued search for and the development of novel compounds that target glutamatergic mechanisms.
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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.