Trial reportJournal of clinical psychopharmacology2012
A Randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder.
Trial report in Journal of clinical psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 5 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 5 syntheses or guidelines pooled it, 213 citations in OpenAlex.
- Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.Frontiers in pharmacology · 2022Pooled it
- Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.The Cochrane database of systematic reviews · 2021Pooled it
- A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.Drug discovery today · 2019Pooled it
- Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2016Pooled it
- Ketamine as a potential treatment for suicidal ideation: a systematic review of the literature.Drugs in R&D · 2015Pooled it
- Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.Journal of affective disorders · 2018Trial
- Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
- A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression.Biological psychiatry · 2013Trial
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Identification of a Class of Novel, Selective, Structurally Distinct GluN2A Negative Allosteric Modulators Through Virtual Screening.ChemMedChem · 2026Article
- Imbalance in excitation and inhibition in sgACC is associated with depression in dementia with Lewy bodies.Translational psychiatry · 2026Article
- Mechanism-Based Polypharmacy as a Repurposing Strategy: The Case of D-Cycloserine and Lurasidone.Clinical and translational science · 2026Review
- Neuropharmacological Insights into Glutamate Homeostasis in Post-stroke Depression Regulated by Astrocytes.Current neuropharmacology · 2026Review
- Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning-Based Advanced Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Beyond NMDA Receptors: A Narrative Review of Ketamine's Rapid and Multifaceted Mechanisms in Depression Treatment.International journal of molecular sciences · 2024Review
- GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice.The international journal of neuropsychopharmacology · 2024Article
- ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
48 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
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Converging lines of evidence suggest that the glutamatergic system may play an increasingly important role in the development of novel therapeutics for major depressive disorder (MDD), particularly agents associated with rapid antidepressant effects. Diverse glutamatergic modulators targeting N-methyl-D-aspartate receptors have shown efficacy in MDD, but their associated psychotomimetic effects presently preclude their use in larger samples. This small, randomized, double-blind, placebo-controlled, crossover pilot study evaluated the potential antidepressant efficacy and tolerability of an oral formulation of the selective N-methyl-D-aspartate NR2B antagonist MK-0657 in patients with treatment-resistant MDD (TRD). The TRD subjects underwent a 1-week drug-free period and were subsequently randomized to receive either MK-0657 monotherapy (4-8 mg/d) or placebo for 12 days. Because of recruitment challenges and the discontinuation of the compound's development by the manufacturer, only 5 of the planned 21 patients completed both periods of the crossover administration of MK-0657 and placebo. Significant antidepressant effects were observed as early as day 5 in patients receiving MK-0657 compared with those receiving placebo, as assessed by the Hamilton Depression Rating Scale and Beck Depression Inventory; however, no improvement was noted when symptoms were assessed with the Montgomery-Asberg Depression Rating Scale, the primary efficacy measure. No serious or dissociative adverse effects were observed in patients receiving this oral formulation of MK-0657. Despite the small sample size, this pilot study suggests that an oral formulation of the NR2B antagonist MK-0657 may have antidepressant properties in TRD patients. Further studies with larger sample sizes are necessary to confirm these preliminary findings.
Indexed as
Identifiers
What OpenQuestion holds
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.