Trial reportThe international journal of neuropsychopharmacology2025
A longitudinal PET study on changes in brain norepinephrine transporter availability following duloxetine treatment in major depressive disorder.
Trial report in The international journal of neuropsychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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
1 citing paper in PubMed.
- Connectome Gradient-Based Subtyping of Major Depressive Disorder Reveals Distinct Neurobiological and Transcriptomic Signatures.Depression and anxiety · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
importanceThe norepinephrine transporter (NET) plays a crucial role in major depressive disorder (MDD). Serotonin and norepinephrine reuptake inhibitors, such as duloxetine, are first-line treatments for MDD. Duloxetine inhibits the reuptake of both serotonin and norepinephrine. However, its precise mechanism, particularly regarding NET occupancy and changes in transporter availability, remains unclear. Norepinephrine transmission, mediated by NET, may be instrumental in treating MDD. Therefore, NET occupancy could serve as a potential biomarker to evaluate treatment efficacy.
objectiveThis study evaluated duloxetine's impact on brain NET availability in patients with MDD using positron emission tomography (PET) with (S,S)-[18F]FMeNER-D2 and its correlation with clinical symptoms using the Hamilton Depression Rating Scale (HAM-D).
designLongitudinal study.
settingPsychiatric hospitals and clinics.
participantsFifteen patients with MDD.
interventionsDuloxetine (20-60 mg daily). MAIN OUTCOMES AND MEASURES: Baseline PET examinations were conducted for all patients, followed by treatment with duloxetine (20-60 mg daily). After 4-6 weeks of duloxetine administration, a second PET examination was performed, and plasma concentrations of duloxetine were measured immediately before and after the second examination using gas chromatography-mass spectrometry. Seven patients showing symptom improvement over the course of time discontinued duloxetine and underwent a third PET examination after a 2-month washout period.
resultsNorepinephrine transporter occupancy by duloxetine was 30%-40% across the doses studied. A paired t-test comparing NET availability before and after duloxetine treatment showed no significant differences, suggesting that duloxetine did not significantly alter NET availability in the short term. Further analysis revealed a significant positive correlation between the change in NET availability and HAM-D scores after treatment. Patients with greater reductions in HAM-D scores exhibited more pronounced reductions in NET availability.
conclusionsThese findings underscore the potential role of NET occupancy by duloxetine in the treatment of MDD and its relationship with clinical outcomes. RELEVANCE: Understanding changes in NET and their implications enhances our comprehension of the complex mechanisms behind antidepressants and may reveal new therapeutic targets for MDD and other neuropsychiatric disorders. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000008251.
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