European Archives of Psychiatry and Clinical Neuroscience最新文献

{"title":"Effectiveness of rTMS compared to SSRI as early treatment of depression - study protocol of a randomized controlled trial (Early-TMS).","authors":"Julia Becker-Sadzio, Bettina Brendel, Simone Weller, Edmund Bornheimer, Ulrike Mehlig, Frank Padberg, Ulrike Vogelmann, Thomas Kammer, Wolfgang Strube, Peter Martus, Andreas J Fallgatter, Christian Plewnia","doi":"10.1007/s00406-025-01975-4","DOIUrl":"10.1007/s00406-025-01975-4","url":null,"abstract":"<p><p>Psychotherapy and antidepressant medication are considered first-line treatment options for major depressive disorder (MDD). However, a high proportion of patients do not respond to initial treatment, underlining the need for alternative treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been established in the treatment of MDD, but the available evidence is limited to forms of MDD with varying degrees of treatment resistance. Randomized-controlled trials (RCT) investigating first-line treatment with rTMS in comparison with first-line antidepressant medication are warranted to further position rTMS within current treatment algorithms for MDD. In this two-stage, therapy response-adapted, randomized multi-center phase 2 rater blinded trial, 106 medication-naïve patients suffering from MDD will be enrolled. In Stage I, participants receive one of the two treatment options for four weeks: either daily bilateral theta burst stimulation (TBS), a patterned and time-saving form of rTMS, or antidepressant medication with selective serotonin reuptake inhibitors (SSRI). The allocation to Stage II occurs therapy response-adapted. Therefore, patients either receive maintenance treatment or will be switched to the respective other treatment arm. Primary outcome is the comparison between the two study arms with regard to therapy response measured by the Montgomery-Asberg Depression Rating Scale (MADRS) after 4 weeks at the end of Stage I. The aim of the study is to provide reliable first evidence and effect size measures of rTMS as first-line treatment compared to SSRI treatment. Positive results will help to implement rTMS in early stages of MDD. Trial registration: ClinicalTrials.gov ID: NCT06545474, August 15, 2024.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1839-1849"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to electroconvulsive therapy is associated with a more diverse oral microbiome- a prospective longitudinal cohort pilot study.","authors":"Christoph Ammer-Herrmenau, Jacob Hamm, Albrecht Neesse, Kilian Günther, Matthias Besse, David Zilles-Wegner","doi":"10.1007/s00406-025-01976-3","DOIUrl":"10.1007/s00406-025-01976-3","url":null,"abstract":"<p><p>Recently it has been shown that psychiatric disorders are associated with changes in the host microbiome. Little is known about the association of electroconvulsive therapy (ECT) and microbiome alterations. In our pilot-study, 15 patients with severe or treatment resistant depression were prospectively recruited and oral swabs were collected pre- and post-ECT. Compared to a control group, ECT did not lead to a significant microbial shift in longitudinal samples (p = 0.65). However, alpha diversity measurements significantly differed between responders and non-responders before ECT (observed species p = 0.014, Shannon p = 0.03) and after ECT (observed species p = 0.015, Shannon p = 0.13).</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1851-1858"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new direction for adjunctive therapy of difficult-to-treat depression: examining the role of orexin receptor antagonists.","authors":"Michael E Thase","doi":"10.1007/s00406-025-01999-w","DOIUrl":"10.1007/s00406-025-01999-w","url":null,"abstract":"<p><p>One of the several pressing unmet needs in the pharmacotherapy of MDD is development of drugs with novel mechanisms of action that can effectively treat depressed patients who do not respond to first- and second-line antidepressants. The value of identifying such a medication would be enhanced if it were also generally well-tolerated and addressed depressive symptoms that are less responsive to SSRIs or SNRIs, such as insomnia or anxiety. This narrative review summarizes the investigation of a novel class of medications originally developed to treat insomnia, the Orexin Receptor Antagonists (ORAs), as adjunctive treatments for depressed patients who have been able to tolerate but who do not obtain an adequate response to standard antidepressants. Although it is likely that the currently approved Dual Orexin Receptor Antagonists (DORAs)-suvorexant, lemborexant and daridorexant-are safe and useful options for concomitant therapy of insomnia in antidepressant-treated patients, these medications have not been approved for this indication. Moreover, DORAs have not been extensively studied as adjunctive therapies for MDD. By contrast, the investigational ORA seltorexant, which is a selective Orexin 2 receptor antagonist, has shown significant antidepressant effects in Phase 2 and Phase 3 trials. Although at least one more unequivocally positive pivotal study will be needed to garner FDA approval for clinical use in the United States, this drug shows promise as a novel and well-tolerated option for patients with difficult to treat depressive episodes.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1611-1619"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: predictors of response to accelerated rTMS in the treatment of treatment-resistant depression.","authors":"Qi Wang, Li Li, Hongyan Zhao, Wenwen Cheng, Gang Cui, Lin Fan, Xiaomei Dong, Tianchao Xu, Zhongli Geng","doi":"10.1007/s00406-024-01951-4","DOIUrl":"10.1007/s00406-024-01951-4","url":null,"abstract":"","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1737"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum ZO-1 and occludin levels in bipolar disorder patients.","authors":"Pınar Aydogan Avşar, Merve Akkuş","doi":"10.1007/s00406-025-02097-7","DOIUrl":"https://doi.org/10.1007/s00406-025-02097-7","url":null,"abstract":"<p><p>Bipolar disorder is a mental illness with a complex and multidimensional etiology. The blood-brain barrier (BBB) is a semi-permeable barrier between the central nervous system (CNS) and peripheral circulation that protects the CNS from external threats. The healthy functioning of the BBB is ensured by tight junctions (TJs) between cells. This research aims to investigate the serum levels of TJ proteins occludin and zonula occludens-1 protein (ZO-1) in bipolar disorder to elucidate etiopathogenesis. This study included 40 BD patients (20 manic episodes, 20 euthymic episodes) and 40 healthy controls. Serum occludin and ZO-1 values were obtained and compared between the two groups. The serum occludin and ZO-1 levels were significantly higher in the bipolar disorder patients. The analysis of covariance (ANCOVA) revealed a significant main effect of groups in the serum occludin and ZO-1 levels and an effect that was independent of age, gender, BMI, and smoking.BBB disruption and neuroinflammation may play a role in bipolar disorder etiopathogenesis. Occludin and ZO-1 may serve as potential biomarkers for BBB leakage in bipolar disorder. Further research may lead to additional pharmacological therapies targeting BBB for drug-resistant bipolar disorder patients.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative pharmacological depression treatment.","authors":"Hans-Jürgen Möller, Rainer Rupprecht, Andreas Reif","doi":"10.1007/s00406-025-02040-w","DOIUrl":"10.1007/s00406-025-02040-w","url":null,"abstract":"","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1537-1538"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining rTMS dosing: EMG-Based motor threshold matters.","authors":"Marco Antonio Cavalcanti Garcia","doi":"10.1007/s00406-025-02025-9","DOIUrl":"10.1007/s00406-025-02025-9","url":null,"abstract":"","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1859-1860"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurosteroids and translocator protein 18 kDa (TSPO) ligands as novel treatment options in depression.","authors":"Marco Riebel, Lisa-Marie Brunner, Caroline Nothdurfter, Simon Wein, Jens Schwarzbach, Philippe Liere, Michael Schumacher, Rainer Rupprecht","doi":"10.1007/s00406-024-01843-7","DOIUrl":"10.1007/s00406-024-01843-7","url":null,"abstract":"<p><p>Recently, the gamma-aminobutyric acid (GABA) system has come into focus for the treatment of anxiety, postpartum depression, and major depressive disorder. Endogenous 3α-reduced steroids such as allopregnanolone are potent positive allosteric modulators of GABA_A receptors and have been known for decades. Current industry developments and first approvals by the U.S. food and drug administration (FDA) for the treatment of postpartum depression with exogenous analogues of these steroids represent a major step forward in the field. 3α-reduced steroids target both synaptic and extrasynaptic GABA_A receptors, unlike benzodiazepines, which bind to synaptic receptors. The first FDA-approved 3α-reduced steroid for postpartum depression is brexanolone, an intravenous formulation of allopregnanolone. It has been shown to provide rapid relief of depressive symptoms. An orally available 3α-reduced steroid is zuranolone, which also received FDA approval in 2023 for the treatment of postpartum depression. Although a number of studies have been conducted, the efficacy data were not sufficient to achieve approval of zuranolone in major depressive disorder by the FDA in 2023. The most prominent side effects of these 3α-reduced steroids are somnolence, dizziness and headache. In addition to the issue of efficacy, it should be noted that current data limit the use of these compounds to two weeks. An alternative to exogenous 3α-reduced steroids may be the use of substances that induce endogenous neurosteroidogenesis, such as the translocator protein 18 kDa (TSPO) ligand etifoxine. TSPO has been extensively studied for its role in steroidogenesis, in addition to other functions such as anti-inflammatory and neuroregenerative properties. Currently, etifoxine is the only clinically available TSPO ligand in France for the treatment of anxiety disorders. Studies are underway to evaluate its antidepressant potential. Hopefully, neurosteroid research will lead to the development of fast-acting antidepressants.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1581-1591"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silexan in anxiety, depression, and related disorders: pharmacological background and clinical data.","authors":"Siegfried Kasper, Anne Eckert","doi":"10.1007/s00406-024-01923-8","DOIUrl":"10.1007/s00406-024-01923-8","url":null,"abstract":"<p><p>We present a narrative review of clinical trials investigating the anxiolytic and antidepressant effects of silexan, an active substance derived from lavender oil and summarize nonclinical findings from pharmacological studies supporting its therapeutic use. Six studies investigated the efficacy of the lavender oil in patients with subthreshold and generalized anxiety disorders as well as in mixed anxiety and depressive disorder (MADD). Furthermore, we present data indicating that silexan may influence sleep quality as well as anxiety or depressive disorders in individuals with post-COVID-19. Silexan taken orally at a daily dose of 80 mg for 10 weeks was significantly superior to placebo in reducing psychic and somatic symptoms of anxiety and was as effective as 0.5 mg/d lorazepam and 20 mg/d paroxetine. In patients with mild or moderate major depression, silexan was superior to placebo and comparably effective to 50 mg/d sertraline. Significant antidepressant effects were also observed in MADD and depression co-morbid with anxiety. The herbal product had a beneficial effect on activities of daily living and health-related quality of life. Adverse events associated with silexan in clinical trials were limited to eructation and mild, transient gastrointestinal complaints. The herbal product was not associated with drug interactions, sedation, sleep disturbance, dependence and abuse potential, sexual dysfunction, weight gain or withdrawal symptoms. Silexan was therefore safe and effective in subthreshold and syndromal anxiety disorders and in major depression.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1621-1635"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esketamine in depression: putative biomarkers from clinical research.","authors":"Jenessa N Johnston, Carlos A Zarate, Mark D Kvarta","doi":"10.1007/s00406-024-01865-1","DOIUrl":"10.1007/s00406-024-01865-1","url":null,"abstract":"<p><p>The discovery of racemic (R, S)-ketamine as a rapid-acting antidepressant and the subsequent FDA approval of its (S)-enantiomer, esketamine, for treatment-resistant depression (TRD) are significant advances in the development of novel neuropsychiatric therapeutics. Esketamine is now recognized as a powerful tool for addressing persistent symptoms of TRD compared to traditional oral antidepressants. However, research on biomarkers associated with antidepressant response to esketamine has remained sparse and, to date, has been largely extrapolated from racemic ketamine studies. Genetic, proteomic, and metabolomic profiles suggest that inflammation and mitochondrial function may play a role in esketamine's antidepressant effects, though these preliminary results require verification. In addition, neuroimaging research has consistently implicated the prefrontal cortex, striatum, and anterior cingulate cortex in esketamine's effects. Esketamine also shows promise in perioperative settings for reducing depression and anxiety, and these effects appear to correlate with increased peripheral biomarkers such as brain-derived neurotrophic factor and serotonin. Further indications are likely to be identified with the continued repurposing of racemic ketamine, providing further opportunity for biomarker study and mechanistic understanding of therapeutic effects. Novel methodologies and well-designed biomarker-focused clinical research trials are needed to more clearly elucidate esketamine's therapeutic actions as well as biologically identify those most likely to benefit from this agent, allowing for the improved personalization of antidepressant treatment.</p>","PeriodicalId":11822,"journal":{"name":"European Archives of Psychiatry and Clinical Neuroscience","volume":" ","pages":"1559-1572"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}