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Record W4407632693 · doi:10.4088/jcp.24m15438

Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder

2025· article· en· W4407632693 on OpenAlexaff
Maurizio Fava, Luca Pani, Sara De Martin, Andrew J. Cutler, Charles W. Gorodetzky, Frank J. Vocci, Frank L. Sapienza, Thomas R. Kosten, Cornelia Kröger, Paggard Champasa, Clotilde Guidetti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E. Inturrisi, Paolo L. Manfredi, M. Pappagallo

Bibliographic record

VenueThe Journal of Clinical Psychiatry · 2025
Typearticle
Languageen
FieldMedicine
TopicTreatment of Major Depression
Canadian institutionsMcGill University
Fundersnot available
KeywordsMajor depressive disorderTerm (time)PsychiatryPsychologyMedicineMood

Abstract

fetched live from OpenAlex

-methyl-D-aspartate receptor (NMDAR) uncompetitive antagonist in development as adjunctive treatment for major depressive disorder (MDD). ). Safety was assessed from adverse events, laboratory parameters, vital signs, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Efficacy assessments used measures of depression, anxiety, sleep, sexual function, cognitive function, and quality of life. The safety population comprised patients who received at least 1 dose of study drug, and the full analysis set (FAS) comprised patients who had at least 1 postbaseline efficacy assessment. and 202 de novo); mean age was 42.9 (13.6) years, and mean baseline Montgomery-Asberg Depression Rating Scale (MADRS10) was 34.5 (4.8). Most common treatment-related treatment emergent adverse events were headache (4.6%), nausea (4.2%), and dizziness (2.6%). There were no signals of meaningful neurological, cardiovascular, metabolic, or sexual adverse events and no case of suicide or suicidal attempt. For the FAS, mean (SD) change from baseline for MADRS10 at 3, 6, 9, and 12 months was -20.1 (10.7), -21.0 (10.8), -21.6 (10.7), and -21.6 (10.4). For the de novo population, mean (SD) was -19.9 (10.0), -19.9 (10.4), -20.1 (10.2), and -22.5 (9.7). Consistent improvements occurred with other tested efficacy measures. Long-term treatment with esmethadone was safe and well tolerated. The antidepressant efficacy of esmethadone was sustained over 12 months. ClinicalTrials.gov identifier: NCT04855760.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.356
Teacher spread0.341 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2025
Admission routes1
Has abstractyes

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