Observational studyEuropean archives of psychiatry and clinical neuroscience2026
Esketamine-based treatment, depression-specific metacognitive training, and their combination in treatment-resistant depression: 6-month trajectories of depressive symptoms and rumination in a multicenter observational study.
Observational study in European archives of psychiatry and clinical neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Treatment-resistant depression (TRD) remains a highly burdensome clinical condition, and improvement in depressive severity does not necessarily imply parallel modification of maladaptive cognitive-affective processes such as rumination. We compared 6-month trajectories of depressive symptoms and depressive rumination across three active treatment conditions in routine clinical care: intranasal esketamine-based treatment without depression-specific metacognitive training (ESK), depression-specific metacognitive training without esketamine exposure (D-MCT), and combined esketamine plus D-MCT (D-MCT + ESK). Of 65 screened patients, 12 were excluded because of at least one absolute contraindication and 53 were enrolled (ESK n = 15, D-MCT n = 12, D-MCT + ESK n = 26). Seven participants did not complete the 6-month endpoint assessment (six in ESK and one in D-MCT + ESK), yielding a complete-case analysis set of 46 patients (ESK n = 9, D-MCT n = 12, D-MCT + ESK n = 25). Generalized estimating equations showed significant time effects and time-by-group interactions for both MADRS and RRS total scores. Endpoint ANCOVA models adjusting for baseline outcome value showed significant group effects at 6 months for MADRS (F(2,42) = 24.97, p<.001) and RRS (F(2,42) = 5.59, p=.007). Six-month MADRS response among completers was 3/9 (33.3%) in ESK, 4/12 (33.3%) in D-MCT, and 23/25 (92.0%) in D-MCT + ESK; corresponding intention-to-treat estimates using non-responder imputation were 3/15 (20.0%), 4/12 (33.3%), and 23/26 (88.5%). Concomitant treatment profiles showed marked imbalance in previous non-pharmacological treatment exposure, representing an important potential confounder. Findings support a cautious, hypothesis-generating interpretation because allocation was nonrandomized, assessment was open-label, the sample was modest, and baseline rumination was higher in the combined group.
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