Clara Miguel,Lingyao Tong,Aran Tajika,Mathias Harrer,Nino de Ponti,Keisuke Yoshimura,Marketa Ciharova,Paul van Haaren,Claudia Buntrock,Andrea Cipriani,Georgia Salanti,Edoardo G Ostinelli,Ioana A Cristea,Pim Cuijpers,Eirini Karyotaki,Toshi A Furukawa
{"title":"Psychotherapy, Antidepressants, and Combined Treatment for Depression: A Network Meta-analysis on Social Functioning Outcomes.","authors":"Clara Miguel,Lingyao Tong,Aran Tajika,Mathias Harrer,Nino de Ponti,Keisuke Yoshimura,Marketa Ciharova,Paul van Haaren,Claudia Buntrock,Andrea Cipriani,Georgia Salanti,Edoardo G Ostinelli,Ioana A Cristea,Pim Cuijpers,Eirini Karyotaki,Toshi A Furukawa","doi":"10.1159/000553252","DOIUrl":"https://doi.org/10.1159/000553252","url":null,"abstract":"INTRODUCTIONSocial functioning is a key component of recovery in depression, yet most research on first-line treatments focuses on symptom reduction, and comparative evidence on social functioning is limited. We aimed to evaluate the comparative effects of psychotherapy, antidepressant medication, and their combination on social functioning in adults with major depression.METHODSWe conducted a systematic review and network meta-analysis of randomised controlled trials up to May 1, 2025. Eligible trials compared psychotherapy, antidepressant medication, combined treatment, and control conditions (placebo, care as usual, waitlist, or no/minimal treatment) in adults with major depression. Effects were calculated as standardised mean differences (SMD) in social functioning instruments (e.g., Sheehan Disability Scale) at post-treatment (mean 12 weeks) and follow-up (mean 32 weeks). Random-effects models were used. We assessed risk of bias and conducted sensitivity analyses. Certainty of evidence was evaluated using CINeMA.RESULTSOf 490 identified trials, 94 (19%; 23,874 participants) reported social functioning and were included. All active treatments outperformed control conditions. Effects varied substantially by control condition type, with waitlist comparisons yielding the largest estimates and comparisons against placebo or care as usual yielding more conservative effects. Combined psychotherapy and pharmacotherapy showed the largest effects versus placebo at post-treatment (SMD 0.75, 95% CI 0.57-0.94) and follow-up (1.08, 0.62-1.54). Psychotherapy and pharmacotherapy did not differ at post-treatment (SMD 0.10, 95% CI -0.05 to 0.25) or follow-up (0.27, 95% CI 0.00-0.54). Certainty of the evidence ranged from moderate to low.CONCLUSIONFirst-line depression treatments support not only symptom reduction but also meaningful participation in daily life. However, only one fifth of trials assessed this outcome, highlighting the need to better integrate patient-valued outcomes into future trials.","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":"106 1","pages":"1-20"},"PeriodicalIF":22.8,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148313587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judith Rohde, Tyler M Moore, Kathryn Walker, Shobi S Ahmed, Henry A MacConnel, Martin Krsak, Scott Shannon, Vivian W L Tsang, Shannon Dames, Marco Buchmann, Birgit Kleim, Erich Seifritz, Sebastian Olbrich, Georgios Schoretsanitis
{"title":"Ketamine-Assisted Psychotherapy for Posttraumatic Stress Disorder: A Systematic Review and Individual Participant Data Meta-Analysis of Predictors of Treatment Effects.","authors":"Judith Rohde, Tyler M Moore, Kathryn Walker, Shobi S Ahmed, Henry A MacConnel, Martin Krsak, Scott Shannon, Vivian W L Tsang, Shannon Dames, Marco Buchmann, Birgit Kleim, Erich Seifritz, Sebastian Olbrich, Georgios Schoretsanitis","doi":"10.1159/000553144","DOIUrl":"10.1159/000553144","url":null,"abstract":"<p><strong>Introduction: </strong>Ketamine combined with psychotherapy has shown promise in treating posttraumatic stress disorder (PTSD), but predictors of clinical benefit remain unclear. In this systematic review and individual participant data meta-analysis (IPDMA), we examined patient- and treatment-level predictors of PTSD symptom change after combined treatment.</p><p><strong>Methods: </strong>Eligible studies combined ketamine with psychotherapy in adults with PTSD. The primary outcome was PTSD symptom change on the PTSD Checklist for DSM-5 (PCL-5). We fit linear mixed-effects models with a random intercept for study and fixed effects for age, sex, baseline PCL-5, number of ketamine sessions, number of psychotherapy sessions, administration route, and treatment duration. Sex-stratified analyses and a quality-restricted sensitivity analysis were conducted.</p><p><strong>Results: </strong>Twelve studies (533 participants) were included; nine were of poor quality. Greater improvement was associated with more psychotherapy (β = 1.03 per session) and more ketamine sessions (β = 1.15 per session), higher baseline symptom severity (β = 0.50 per PCL-5 point), and shorter treatment duration (β = -0.58 per week). Between-study heterogeneity was nontrivial (intraclass correlation coefficient ≈ 0.15). In sex-stratified models, number of psychotherapy sessions, baseline severity, and shorter treatment duration remained associated with improvement in both sexes. In the sensitivity analysis (n = 63), baseline severity was the only significant predictor of treatment outcome.</p><p><strong>Conclusion: </strong>Higher baseline PTSD severity was the most robust predictor of symptom reduction. Session intensity and treatment timing may matter, but associations should be interpreted cautiously given the predominance of poor-quality studies and require replication in prospective trials with standardized protocols and longer follow-up.</p>","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-13"},"PeriodicalIF":9.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eva Rothermund-Nassir, Nicole Rosalinde Hander, Christoph Kröger, Yesim Erim, Volker Köllner, Peter Angerer, Harald Gündel
{"title":"Clarifying Scope and Interpretation of Psychotherapeutic Consultation at Work: A Response to Recent Commentary.","authors":"Eva Rothermund-Nassir, Nicole Rosalinde Hander, Christoph Kröger, Yesim Erim, Volker Köllner, Peter Angerer, Harald Gündel","doi":"10.1159/000553033","DOIUrl":"10.1159/000553033","url":null,"abstract":"","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-2"},"PeriodicalIF":9.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thorsten Barnhofer, Maria Niemi, Johannes Michalak, Maria Velana, J Mark G Williams, Alberto Chiesa, Stuart J Eisendrath, Kevin L Delucchi, Zindel V Segal, Mira Cladder-Micus, Anne Speckens, Mauro Garcia-Toro, Jesus Montero-Marin, Barnaby D Dunn, Clara Strauss, Florian A Ruths, Mary Ryan, Allan H Young, Pim Cuijpers, Mathias Harrer
{"title":"Efficacy and Moderators of Mindfulness-Based Cognitive Therapy in Difficult-to-Treat Depression: A Systematic Review and Individual Participant Data Meta-Analysis.","authors":"Thorsten Barnhofer, Maria Niemi, Johannes Michalak, Maria Velana, J Mark G Williams, Alberto Chiesa, Stuart J Eisendrath, Kevin L Delucchi, Zindel V Segal, Mira Cladder-Micus, Anne Speckens, Mauro Garcia-Toro, Jesus Montero-Marin, Barnaby D Dunn, Clara Strauss, Florian A Ruths, Mary Ryan, Allan H Young, Pim Cuijpers, Mathias Harrer","doi":"10.1159/000552831","DOIUrl":"10.1159/000552831","url":null,"abstract":"<p><strong>Introduction: </strong>Around a third of patients with major depressive disorder experience persistent symptoms despite usual treatments. Identifying scalable psychological treatment options is critical to reduce the burden associated with difficult-to-treat depression (DTD). We examined the efficacy of mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU) and other active psychosocial controls in current DTD, and explored potential moderators.</p><p><strong>Methods: </strong>We conducted an individual patient data (IPD) meta-analysis of randomised controlled trials comparing MBCT with TAU or other active psychosocial controls in currently depressed adults meeting criteria for treatment non-response, treatment resistance, or chronic course. Seven studies (N = 777) contributed data. Bayesian one-stage models were used as primary approach to estimate pooled effects on depressive symptom severity.</p><p><strong>Results: </strong>MBCT was likely superior to TAU at post-treatment (standardised mean difference = -0.40; 95% credible interval [CrI] = -0.64 to -0.16) and medium-term follow-up (-0.41; 95% CrI = -0.76 to -0.02), with posterior probabilities of 92% and 85% of surpassing a clinical relevance threshold of d = -0.24, respectively. In contrast, comparative effects relative to other psychosocial interventions were uncertain, with no evidence of superiority. Moderator analyses did not identify robust predictors of outcome, suggesting broadly consistent effects across baseline severity, chronicity, and comorbidity.</p><p><strong>Conclusion: </strong>MBCT appears to be an effective and safe option for DTD, superior to TAU, with benefits maintained at medium-term follow-up, although no evidence of superiority over other active psychosocial interventions was observed. These findings support the integration of MBCT into comprehensive treatment models for DTD.</p>","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-16"},"PeriodicalIF":9.0,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Does Fatigue in Patients with Post-COVID-19 Syndrome Improve with Rehabilitation?","authors":"René Garbsch, Frank C Mooren, Boris Schmitz","doi":"10.1159/000552983","DOIUrl":"10.1159/000552983","url":null,"abstract":"","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-3"},"PeriodicalIF":9.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paula Rehm, Marius Gruber, Kira F Ahrens, Henry Staub, Franka Timm, Lea Krätzig, Stefanie Fischer, Sharmili Edwin Thanarajah, Max Berg, Janik Goltermann, Nils Ralf Winter, Katharina Thiel, Tiana Borgers, Hannah Meinert, Linda M Bonnekoh, Kira Flinkenflügel, Jochen Bauer, Frederike Stein, Florian Thomas-Odenthal, Paula Usemann, Lea Teutenberg, Igor Nenadić, Benjamin Straube, Nina Alexander, Hamidreza Jamalabadi, Andreas Jansen, Nils Opel, Susanne Meinert, Dominik Grotegerd, Tim Hahn, Elisabeth J Leehr, Elisabeth Schramm, Moritz Elsaesser, Winfried Rief, Andreas Reif, Tilo Kircher, Udo Dannlowski, Jonathan Repple
{"title":"Distinguishing Chronic and Non-Chronic Depression: A Clinical Profile and Symptom Networks Approach.","authors":"Paula Rehm, Marius Gruber, Kira F Ahrens, Henry Staub, Franka Timm, Lea Krätzig, Stefanie Fischer, Sharmili Edwin Thanarajah, Max Berg, Janik Goltermann, Nils Ralf Winter, Katharina Thiel, Tiana Borgers, Hannah Meinert, Linda M Bonnekoh, Kira Flinkenflügel, Jochen Bauer, Frederike Stein, Florian Thomas-Odenthal, Paula Usemann, Lea Teutenberg, Igor Nenadić, Benjamin Straube, Nina Alexander, Hamidreza Jamalabadi, Andreas Jansen, Nils Opel, Susanne Meinert, Dominik Grotegerd, Tim Hahn, Elisabeth J Leehr, Elisabeth Schramm, Moritz Elsaesser, Winfried Rief, Andreas Reif, Tilo Kircher, Udo Dannlowski, Jonathan Repple","doi":"10.1159/000552901","DOIUrl":"10.1159/000552901","url":null,"abstract":"<p><strong>Introduction: </strong>Different disorder courses contribute to the large heterogeneity within depressive syndromes. Chronic depression (CD) warrants further investigation given its high prevalence and poor treatment outcomes. This study aimed to identify a clinical profile and symptomatic phenotype associated with CD versus non-chronic depression (NCD) to provide a better characterization of CD.</p><p><strong>Methods: </strong>The preregistered analysis used cross-sectional data from a large German cohort (N = 994; 64.9% female) with retrospective information on depression trajectories. We assessed associations of nine psychological and social characteristics with CD in logistic regression models. We further examined symptom networks across disorder courses using Bayesian network analysis of Beck Depression Inventory (BDI-I) item-level data.</p><p><strong>Results: </strong>In our sample 18.5% of patients with depression met criteria for CD (n<sub>CD</sub> = 184), whereas 81.5% showed a non-chronic course (n<sub>NCD</sub> = 810). The characteristics childhood maltreatment, age of onset, neuroticism, extraversion, social networks, social support, psychosocial functioning, and psychiatric comorbidities were associated with CD in single regressions. In a combined model (R2 = 0.25), greater exposure to childhood maltreatment, lower extraversion, and lower psychosocial functioning were associated with CD, defining a clinical profile distinguishing CD from NCD. Symptom networks based on BDI-I items were highly similar across trajectories, differing only by the connection between past failure and self-contempt, which was unique to the CD group.</p><p><strong>Conclusion: </strong>Psychosocial factors, but not symptom profiles, distinguished CD from NCD. Thus, characteristics beyond classical depression symptoms seem more informative for differentiating depression trajectories. If confirmed longitudinally, these findings may improve prediction of depression trajectories and inform early intervention.</p>","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-15"},"PeriodicalIF":9.0,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bella Bingbing Zhang, Tim Tianze Lin, Penny Ping Qin, Rebecca Laidi Kan, Adam Weili Xia, Minxia Jin, Yinghu Peng, Daniel Keeser, Frank Padberg, Martin Tik, Tifei Yuan, Benjamin Becker, Frank Fan Zhu, Georg S Kranz
{"title":"How Standardized Is Transcranial Magnetic Stimulation Treatment for Depression? Large-Cohort Modeling Reveals Systematic Dosimetric Variability.","authors":"Bella Bingbing Zhang, Tim Tianze Lin, Penny Ping Qin, Rebecca Laidi Kan, Adam Weili Xia, Minxia Jin, Yinghu Peng, Daniel Keeser, Frank Padberg, Martin Tik, Tifei Yuan, Benjamin Becker, Frank Fan Zhu, Georg S Kranz","doi":"10.1159/000552942","DOIUrl":"10.1159/000552942","url":null,"abstract":"<p><strong>Introduction: </strong>Repetitive transcranial magnetic stimulation (rTMS) is a widely utilized, noninvasive brain stimulation technique for treating neurological and psychiatric disorders worldwide. The efficacy of rTMS is influenced by individual head morphology, which shapes the induced electric field (E-field) in the brain. The standard practice for dosing rTMS involves adjusting the intensity to a defined percentage of the motor threshold (MT), a method exemplified by the globally adopted, US FDA-approved protocol of using 120% MT for depression. Since head morphology varies systematically across ethnic groups, current dosing protocols may lead to inconsistent cortical dosing.</p><p><strong>Methods: </strong>Here, we used large-scale computational modeling (N = 1,085) to systematically evaluate TMS dosage across \"White,\" \"Han Chinese,\" and \"Black or African Am.\"</p><p><strong>Populations: </strong></p><p><strong>Results: </strong>Our findings reveal striking ethnic disparities in the E-field ratio between the therapeutic target (left dorsolateral prefrontal cortex, DLPFC) and the calibration site (left primary motor cortex, M1). \"Han Chinese\" individuals exhibited a significantly higher E-field ratio (E-field<sub>DLPFC</sub>/E-field<sub>M1</sub> = 1.226) compared to \"White\" individuals (E-field<sub>DLPFC</sub>/E-field<sub>M1</sub> = 1.096). These differences are primarily driven by variations in scalp-to-cortex distance (SCD). Based on these findings, we derived both simplified population-level adjustment formulas and individualized SCD-based dosing equations and implemented them in a web-based tool for practical use.</p><p><strong>Conclusion: </strong>Our results suggest that applying a uniform multiplier of MT to DLPFC stimulation may introduce systematic differences in delivered cortical dose across ethnic populations, highlighting that universal dosing conventions derived predominantly from specific demographic cohorts may embed bias, such that established safety and efficacy profiles may not be uniformly applicable across diverse global populations.</p>","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-17"},"PeriodicalIF":9.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13299130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julian Reichert, Armin Drusko, Eva Beiner, Michelle Hermes, Vassilios Papaioannou, Winfried Häuser, Wolfgang Eich, Jonas Tesarz
{"title":"Symptom-Level Comorbidity of Fibromyalgia and Depression: A Network Approach within a Large Clinical Sample.","authors":"Julian Reichert, Armin Drusko, Eva Beiner, Michelle Hermes, Vassilios Papaioannou, Winfried Häuser, Wolfgang Eich, Jonas Tesarz","doi":"10.1159/000551679","DOIUrl":"10.1159/000551679","url":null,"abstract":"<p><strong>Introduction: </strong>Fibromyalgia syndrome (FMS) and major depressive disorder (MDD) frequently co-occur together, but the mechanisms linking these conditions remain poorly understood. This study aimed to delineate symptom clusters within the FMS-MDD network, identify bridging symptoms connecting these clusters, and evaluate the integrative role of Pain Intensity.</p><p><strong>Methods: </strong>Cross-sectional data from 3,044 patients with FMS (94% female; mean age = 52.4, SD = 9.28) were analyzed using a mixed graphical model. From an initial pool of 238 items, 30 symptom nodes were selected through a systematic reduction process.</p><p><strong>Results: </strong>The analysis revealed seven distinct symptom clusters: Pain Intensity and Functional Impact, Autonomic and Somatic Complaints, Trauma and Anxiety-driven Symptomatology, Sexual and Health Concerns, Anhedonia and Social Disconnection, Cognitive-Affective and Psychomotor Dysfunctions, and Sleep, Energy Levels, and Social Functioning. Six symptoms were identified as key bridges between clusters, with depressed mood (z = 2.43), fatigue (z = 2.06), and anxiety and nervousness (z = 2.09) showing the highest bridge centrality. Surprisingly, pain intensity exhibited minimal connectivity, ranking 18th in bridge strength (z = - 0.59), and primarily linked to sleeping problems and fatigue.</p><p><strong>Conclusion: </strong>Our findings suggest that emotional and fatigue-related symptoms play a more central role in linking FMS and depression than Pain Intensity alone. Bridge symptoms such as fatigue and depressed mood may represent clinically meaningful targets for symptom-focused interventions. As this study is cross-sectional, causal inferences cannot be drawn. Longitudinal studies are needed to examine temporal dynamics and test whether targeting bridge symptoms improves clinical outcomes.</p>","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-17"},"PeriodicalIF":9.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lea J Mertens, Felix Betzler, Manuela Brand, Ricarda Evens, Andrea Jungaberle, Henrik Jungaberle, Laura Kärtner, Tomislav Majić, Christian N Schmitz, Andreas Ströhle, Dennis Scharf, Moritz Spangemacher, Max Wolff, Zahra Assadi, Scharif Bahri, Lilith Becher, Luca V Färber, Henry Harder, Niklas Kirchen, Eugenia Kulakova, Linda C Kunz, Andy Meijer, Barbara Rohrmoser, Stefan Wellek, Moritz M Berger, Michael Koslowski, Gerhard Gründer
{"title":"Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression: 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial.","authors":"Lea J Mertens, Felix Betzler, Manuela Brand, Ricarda Evens, Andrea Jungaberle, Henrik Jungaberle, Laura Kärtner, Tomislav Majić, Christian N Schmitz, Andreas Ströhle, Dennis Scharf, Moritz Spangemacher, Max Wolff, Zahra Assadi, Scharif Bahri, Lilith Becher, Luca V Färber, Henry Harder, Niklas Kirchen, Eugenia Kulakova, Linda C Kunz, Andy Meijer, Barbara Rohrmoser, Stefan Wellek, Moritz M Berger, Michael Koslowski, Gerhard Gründer","doi":"10.1159/000552272","DOIUrl":"10.1159/000552272","url":null,"abstract":"<p><strong>Introduction: </strong>Psilocybin shows promise for treatment-resistant depression (TRD), but long-term data are limited. This study examined the antidepressant effect of one or two doses of psilocybin with adjunct psychotherapy in TRD until 12 months.</p><p><strong>Methods: </strong>This is a naturalistic follow-up of a phase 2b, randomized, active placebo-controlled trial in adults with TRD, where participants were randomized to receive two drug administrations 6 weeks apart, embedded within seven psychotherapeutic sessions: (1) active placebo (100 mg nicotinamide), then 25 mg psilocybin, (2) 5 mg psilocybin, then 25 mg psilocybin, (3a) 25 mg psilocybin, then 5 mg psilocybin, or (3b) 25 mg psilocybin twice. The controlled phase ended at 12 weeks, after which participants could pursue other treatments, with follow-ups at 6 and 12 months. The primary follow-up endpoint was change from baseline on the Hamilton Rating Scale for Depression (HAMD17).</p><p><strong>Results: </strong>Overall, 126/144 randomized participants (51 females, 40%) completed at least one follow-up visit. Mean baseline HAMD17 scores across groups ranged from 21.6 to 22.2. A generalized additive mixed regression model for change in HAMD17 scores showed a significant time effect across groups for both follow-up time points, with estimated average changes from baseline of -7.93 (95% CI: -9.17 to -6.70, adj. p < 0.0001) at 6 months and -7.74 (95% CI: -9.04 to -6.43, adj. p < 0.0001) at 12 months, without significant group differences. Results were consistent when controlling for antidepressant pharmacotherapy and psychedelic use. Re-initiation of antidepressant pharmacotherapy during follow-up was strongly associated with higher HAMD17 scores (β = 3.79, 95% CI: 1.98 to 5.60).</p><p><strong>Conclusion: </strong>This is the largest and most complete systematic follow-up of any clinical psychedelic trial. The findings demonstrate a stable and clinically meaningful long-lasting antidepressant effect of one or two 25 mg doses psilocybin with adjunct psychotherapy up to 12 months in TRD.</p>","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-18"},"PeriodicalIF":9.0,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter Lilliengren, Malin Ljungdahl, Mattias Rööst, Fredrik Falkenström, Joel Town, Daniel Maroti
{"title":"Response to the Letter to the Editor regarding \"Online Intensive Short-Term Dynamic Psychotherapy for Treatment-Resistant Somatic Symptom Disorder: An Interrupted Time-Series Study\".","authors":"Peter Lilliengren, Malin Ljungdahl, Mattias Rööst, Fredrik Falkenström, Joel Town, Daniel Maroti","doi":"10.1159/000552639","DOIUrl":"10.1159/000552639","url":null,"abstract":"","PeriodicalId":20744,"journal":{"name":"Psychotherapy and Psychosomatics","volume":" ","pages":"1-2"},"PeriodicalIF":9.0,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}