Clinical Psychopharmacology and Neuroscience最新文献

{"title":"LGALS9 Is Beneficial to the Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation on Ischemic Stroke.","authors":"Jinlian Huang, Jun Wu, Lishan Huang, Xia Wu","doi":"10.9758/cpn.25.1366","DOIUrl":"10.9758/cpn.25.1366","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate whether LGALS9 contributes to the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of ischemic stroke (IS) in rats.</p><p><strong>Methods: </strong>The model of cerebral ischemia in rats was established via middle cerebral artery occlusion (MCAO). After being injected with LGALS9 siRNA prior to MCAO surgery and undergoing rTMS intervention postoperatively, the rats were evaluated for neurological function using the modified neurological severity score (mNSS) and for behavioral function through the foot-fault test and Rotarod test. Brain tissues were collected, and pathological changes were observed. Levels of IL-1β, IL-6, and IL-18 were assessed using ELISA. Immunohistochemistry was employed to detect CD86 expression, while RT-qPCR and Western blot were used to detect LGALS9 expression.</p><p><strong>Results: </strong>MCAO rats showed higher mNSS scores, more foot-fault errors, shorter Rotarod duration, elevated IL-6, IL-18, and IL-1β levels, decreased LGALS9 expression, increased CD86 expression, severe brain damage with increased apoptotic neurons, and elevated neuropathological injury scores. rTMS intervention improved the neurological function of MCAO rats and alleviated the inflammatory response in brain tissues, and LGALS9 enhanced the improvement effects induced by the rTMS intervention.</p><p><strong>Conclusion: </strong>rTMS can improve neurological function, reduce inflammatory responses, and protect brain tissue in rats with IS, effects for which LGALS9 is required to achieve the full benefit. The molecular mechanisms of the rTMS‑LGALS9 pathway remain unclear, as its downstream signaling and effects on neurological function and inflammation are not fully elucidated. Moreover, findings from animal models require further validation for human disease relevance and clinical translation.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"513-525"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supraventricular Tachycardia in an Adolescent with Acute Psychotic Disorder Treated with Olanzapine: A Rare Event Managed with Aripiprazole.","authors":"Müge Mutlu, Begüm Kırmızı, Pınar Aydoğan Avşar, Merve Ergüven Demirtaş, Esra Çöp","doi":"10.9758/cpn.25.1384","DOIUrl":"10.9758/cpn.25.1384","url":null,"abstract":"<p><p>Olanzapine is an atypical antipsychotic that is effective for treating first-episode psychosis in adolescents. The risk of QTc prolongation is generally regarded as low; however, rare but clinically significant cardiac conduction abnormalities have been documented. To the best of our knowledge, this report presents the first documented case of supraventricular tachycardia and significant ST-segment depression observed during treatment with therapeutic-dose olanzapine, with only one similar case previously reported in an adult patient. A 16-year-old girl was admitted to the inpatient service with an acute psychotic disorder. Fourteen days after titration to olanzapine 10 mg/day, the patient experienced sudden palpitations, presenting with a heart rate of 240 beats per minute and ST-segment depression on electrocardiography (ECG). Olanzapine was promptly discontinued, and cardiac rhythm was subsequently normalized. In light of persistent psychotic symptoms, the medication was switched to aripiprazole at a daily dose of 20 mg. Subsequent evaluations showed marked improvement in psychopathology with no recurrence of cardiac abnormalities.This case report highlights the possibility of clinically significant cardiac arrhythmias temporally associated with therapeutic doses of olanzapine. These findings highlight the importance of careful cardiovascular monitoring, including ECG evaluation, in adolescents undergoing antipsychotic treatment.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"656-660"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Employment Status Shapes the Link between Serum Tumor Necrosis Factor and Suicidal Ideation in Patients with Acute Coronary Syndrome: Evidence from an Independent Clinical Cohort.","authors":"Hee-Ju Kang, Ju-Wan Kim, Sung-Wan Kim, Min-Chul Kim, Youngkeun Ahn, Myung Ho Jeong, Jae-Min Kim","doi":"10.9758/cpn.26.1411","DOIUrl":"10.9758/cpn.26.1411","url":null,"abstract":"<p><strong>Objective: </strong>Building on our prior observation in a depression cohort that employment status may modify the association between serum tumor necrosis factor-alpha (TNF-α) and suicidal ideation (SI), we examined whether a similar context-dependent association is present in an independent cohort of patients with acute coronary syndrome (ACS).</p><p><strong>Methods: </strong>Methods: We analyzed 969 consecutively enrolled ACS patients assessed 2 weeks after diagnosis (baseline). Serum TNF-α was quantified at baseline and dichotomized at the cohort median (48.14 pg/ml) into lower vs. higher groups. Employment status was classified as employed vs. unemployed. SI was evaluated at baseline and again at 1-year follow-up among 711 participants. Binary logistic regression examined independent and interactive associations of TNF-α (binary and ln-transformed continuous) and employment with SI, adjusting for sociodemographic, psychiatric, and cardiac covariates.</p><p><strong>Results: </strong>Contrastingly to the depression cohort, higher TNF-α independently predicted SI, while employment status showed no independent association. However, a significant TNF-α × employment interaction at both timepoint was confirmed, with the highest risk found in unemployed patients with elevated TNF-α.</p><p><strong>Conclusion: </strong>This study in patients with ACS supports employment status as an important contextual modifier of the association between serum TNF-α and SI across clinical populations. The independent contribution of inflammation may be more evident in medically ill populations with acute inflammatory activation. Combining a routinely available cytokine measure with employment information may help identify high-risk subgroups after ACS.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"650-655"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Lithium Enhances Klotho Expression and Mitochondrial Size and Branching in Human Cardiac Fibroblasts Involving Nuclear Factor-kappa B Inhibition.","authors":"Pao-Huan Chen, Ting-Wei Lee, Shuen-Hsin Liu, Tzu-Yu Cheng, Yu-Hsun Kao, Yi-Jen Chen","doi":"10.9758/cpn.25.1392","DOIUrl":"10.9758/cpn.25.1392","url":null,"abstract":"<p><strong>Objective: </strong>Emerging studies suggest that lithium might be cardioprotective. Although studies have suggested that lithium improves mitochondrial dysfunction, promotes antiaging processes, and reduces cardiac fibrosis, whether lithium modulates Klotho, an antiaging protein, and mitochondrial morphology in human cardiac fibroblasts remains unclear. This study investigated the effects of therapeutic lithium on Klotho expression and mitochondrial morphology in human cardiac fibroblasts and underlying mechanisms.</p><p><strong>Methods: </strong>We conducted microRNA sequencing, pathway enrichment analysis, mitochondrial morphology assessment, real-time reverse-transcription polymerase chain reaction, western blotting, and migration assay upon human cardiac fibroblasts and myocardial tissues of rats subjected to mania model.</p><p><strong>Results: </strong>Transcriptomic analysis of myocardial tissues from rats subjected to mania model unveiled that the significantly enriched pathways targeted by lithium were related to mitochondrial function. Mitochondrial morphology assessment showed that human cardiac fibroblasts treated with LiCl (1.0 mmol/L) for 48 hours exhibited greater mitochondrial area, perimeter length, and degree and length of branching than did control fibroblasts. Additionally, the messenger RNA and protein expression levels of Klotho were upregulated in human cardiac fibroblasts treated with LiCl (1.0 mmol/L) for 48 hours compared with control fibroblasts, whereas the levels of phosphorylated nuclear factor-kappa B (NF-κB) p65 were downregulated. Furthermore, human cardiac fibroblasts treated with the combination of LiCl (1.0 mmol/L) and Bay 11-7802 (3 μM) exhibited similar migration ability and mitochondrial size and branching relative to LiCl (1.0 mmol/L)-treated fibroblasts.</p><p><strong>Conclusion: </strong>Lithium at a therapeutic concentration enhances Klotho expression and mitochondrial size and branching in human cardiac fibroblasts probably through NF-κB inhibition.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"597-608"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Meta-analysis of Randomized Controlled Trials of Functional Magnetic Resonance Imaging Neurofeedback for Training of Attention and Related Cognitive Functions.","authors":"Ying-Hsin Chen, Shun-Chin Liang, Cheuk-Kwan Sun, Yu-Shian Cheng, Chia-Min Chen, Kuo-Chuan Hung","doi":"10.9758/cpn.26.1405","DOIUrl":"10.9758/cpn.26.1405","url":null,"abstract":"<p><strong>Objective: </strong>This meta-analysis investigated the effects of functional magnetic resonance imaging neurofeedback (fMRI-NF) on inattention and cognitive dysfunctions.</p><p><strong>Methods: </strong>Using the keywords \"fMRI neurofeedback\" and \"attention,\" randomized controlled trials were identified from major electronic databases from inception to June 2024. Outcomes were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Five studies including 214 participants (mean age = 16.8 years) were analyzed. The median number of fMRI-NF sessions was four (range: 3-15), and the median follow-up duration was three weeks (range: 1-10 weeks). Stimulation sites included the right inferior frontal gyrus (n = 2), right anterior insular cortex (n = 1), dorsal anterior cingulate cortex (n = 1), and an individualized approach (n = 1). The primary analysis showed no significant difference in inattention improvement between the fMRI-NF and control groups (SMD = 0.17, 95% CI: -0.15 to 0.49, <i>p</i> = 0.30; four studies, 153 participants). Secondary outcomes also showed no significant intergroup differences, including vigilance (SMD = 0.08, 95% CI: -0.49 to 0.65, <i>p</i> = 0.79), inhibition (SMD = -0.68, 95% CI: -2.11 to 0.74, <i>p</i> = 0.35), and processing speed (SMD = -0.56, 95% CI: -1.38 to 0.27, <i>p</i> = 0.19). Heterogeneity was greater for the secondary outcomes than for the primary outcome, with I² values of 49% for vigilance, 90% for inhibition, and 79% for processing speed, compared with 0% for the primary outcome.</p><p><strong>Conclusion: </strong>Given the limited evidence available to date, current evidence remains insufficient to draw robust conclusions regarding the therapeutic effectiveness of fMRI-NF.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"470-479"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Wnt Pathway Regulators in Adolescents with Suicidal Behavior Disorder and Nonsuicidal Self-injury Disorder: A Case-control Study.","authors":"Elif Nur Yaşar, Hurşit Ferahkaya, İbrahim Kılınç, Abdullah Akkuş, Ömer Faruk Akça","doi":"10.9758/cpn.26.1419","DOIUrl":"10.9758/cpn.26.1419","url":null,"abstract":"<p><strong>Objective: </strong>The Wnt/β-catenin pathway plays a critical role in neuroplasticity and neurogenesis. The present study aimed to investigate whether circulating regulators of the Wnt/β-catenin pathway-Porcupine, Notum, and Dickkopf-1-differ in adolescents diagnosed with suicidal behavior disorder (SBD) and nonsuicidal self-injury disorder (NSSID) compared with control group.</p><p><strong>Methods: </strong>This case-control study included adolescents aged 12 to 18 years: SBD (n = 41), NSSID (n = 40), and control group (n = 40). Diagnoses were established according to DSM-5 Section III criteria, and psychiatric comorbidities were assessed using the K-SADS-PL. Serum concentrations of Porcupine, Notum, and Dickkopf-1 were measured by ELISA. The Revised Child Anxiety and Depression Scale was used to evaluate the severity of psychiatric symptoms.</p><p><strong>Results: </strong>Serum Porcupine and Notum levels were significantly higher in both the SBD and NSSID groups than in control group, and these differences remained significant after adjusting for age and sex. In contrast, Dickkopf-1 levels did not differ between groups. When patients were reclassified according to psychotropic medication use, Porcupine and Notum levels remained elevated compared with control group in both medication users and non-users. Within the patient groups, no significant correlations were observed between biomarker levels and symptom scores.</p><p><strong>Conclusion: </strong>Elevated serum Porcupine and Notum levels-modulators of the Wnt/β-catenin pathway-characterize adolescents with SBD and NSSID and are consistent with a potential shared biological substrate across self-harm phenotypes. Longitudinal, multicenter studies integrating central and peripheral measures are needed to clarify causality and clinical utility.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"617-626"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 21-year Comparative Study of Prescriptions of Benzodiazepines and Selective Serotonin Reuptake Inhibitors and Related Drugs in a Japanese University Hospital.","authors":"Mutsuhiro Nakao, Hokuto Morohoshi, Yumiko Kurata, Akiou Nakamura","doi":"10.9758/cpn.26.1407","DOIUrl":"10.9758/cpn.26.1407","url":null,"abstract":"<p><strong>Objective: </strong>Benzodiazepines (BZPs) continue to be widely prescribed in non-psychiatric settings, despite clinical guideline recommendations favouring selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) for the treatment of anxiety and depressive disorders. Long-term, hospital-based evidence comparing these prescribing patterns in Japan remains limited. The study aim was to evaluate long-term trends in BZP prescribing relative to SSRI/SNRI use and to identify factors associated with anxiolytic BZP versus SSRI/SNRI prescriptions.</p><p><strong>Methods: </strong>We conducted a database study of all 16,886,524 prescriptions issued between April 2001 and March 2022 at a tertiary university hospital in Japan. Anxiolytic and hypnotic BZPs, SSRIs, SNRIs, and related antidepressants were identified. The ratio of anxiolytic BZP to SSRI/SNRI prescriptions (B/S ratio) was calculated according to department group. Factors associated with anxiolytic BZP versus SSRI/SNRI prescribing were examined using multiple logistic regression analysis.</p><p><strong>Results: </strong>Anxiolytic BZP prescriptions accounted for 2.3% of all prescriptions and declined over time, whereas SSRI/SNRI prescriptions (1.4%) remained largely stable throughout the study period. The B/S ratio was consistently higher in internal medicine than in psychiatry, although a gradual reduction was observed over time. Multivariable analysis demonstrated that anxiolytic BZP prescribing was independently associated with the internal medicine department, female sex, outpatient status, younger age, and earlier calendar years.</p><p><strong>Conclusion: </strong>Despite a temporal decline, anxiolytic BZPs continue to be preferentially prescribed over SSRIs/SNRIs in non-psychiatric settings. These findings underscore persistent gaps between evidence-based recommendations and clinical practice and highlight the need for targeted educational and policy interventions to optimise psychotropic prescribing.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"609-616"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of Somatic Symptom Severity in Adult Psychiatric Outpatients: A Cross-sectional Heart Rate Variability and Quantitative Electroencephalography Study.","authors":"Hye Ri Kim, Doug Hyun Han, Sun Mi Kim","doi":"10.9758/cpn.25.1358","DOIUrl":"10.9758/cpn.25.1358","url":null,"abstract":"<p><strong>Objective: </strong>To examine the relative contributions of clinical, autonomic, and neurophysiological variables to somatic symptom severity among adults with major depressive disorder (MDD) or attention-deficit/hyperactivity disorder (ADHD).</p><p><strong>Methods: </strong>We analyzed data from 103 outpatients (MDD = 55; ADHD = 48) who completed quantitative electroencephalography (QEEG), heart rate variability (HRV), and questionnaires (Patient Health Questionnaire-15, Beck Depression Inventory-II, Pittsburgh Sleep Quality Index, Korean Adult ADHD Rating Scale). Hierarchical regression models sequentially entered demographics, clinical symptoms, HRV total power, and QEEG beta-band coherence.</p><p><strong>Results: </strong>The final model explained 49.4% of the variance (adjusted R² = 0.421, <i>p</i> < 0.001). Clinical variables produced the largest increment (ΔR² = 0.232, <i>p</i> < 0.001), with sleep disturbance as the strongest predictor (β = 0.359, <i>p</i> < 0.001), followed by female sex (β = 0.256, <i>p</i> = 0.004) and depressive symptoms (β = 0.207, <i>p</i> = 0.031). Lower HRV total power was significantly associated with greater somatic symptom severity (ΔR² = 0.026, <i>p</i> = 0.034; β = -0.194, <i>p</i> = 0.020). Reduced QEEG beta coherence added value (ΔR² = 0.076, <i>p</i> = 0.048), particularly for right frontofrontal (β = -0.259, <i>p</i> = 0.031) and left frontoparietal (β = -0.245, <i>p</i> = 0.052) connectivity. Primary diagnosis (MDD vs. ADHD) was not predictive (<i>p</i> = 0.124).</p><p><strong>Conclusion: </strong>Sleep disturbance showed the strongest association with somatic symptoms, followed by female sex and depressive symptoms. Limited role of categorical diagnosis supports a dimensional framework. Reduced autonomic flexibility and disrupted cortical connectivity may underlie bodily distress, warranting confirmation through longitudinal studies.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"501-512"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Efficacy of Interventions for the Prevention and Treatment of Postpartum Depression: A Bayesian Network Meta-analysis.","authors":"Archana Mishra, Krishna Nikhila Bonga, Biswa Ranjan Mishra, Anand Srinivasan, Rituparna Maiti, Debasish Hota","doi":"10.9758/cpn.26.1404","DOIUrl":"10.9758/cpn.26.1404","url":null,"abstract":"<p><p>Postpartum depression (PPD) is a highly prevalent but under-reported and undertreated disorder that affects mothers and infants alike. The management of PPD has to be thoughtfully catered to limit the exposure of infants to harmful drugs. This network meta-analysis (NMA) was conducted to assess the efficacy of pharmacological interventions for the prevention and treatment of PPD. We searched PubMed/MEDLINE, EMBASE, Scopus, Google Scholar, Cochrane databases and clinical trial registries to find studies to be included, and data were extracted. Random effects Bayesian NMA was performed using Markov chain Monte Carlo simulations. A network graph was built, the rank probability of each treatment was determined, and the surface under the cumulative rank probability curve was calculated. The risk of bias assessment, including publication bias, was assessed. Data from 54 studies, including 7,438 participants, were included for this NMA. No pharmacological intervention demonstrated robust superiority over placebo for the treatment of PPD, though wide credible intervals (CrI) and limited sample sizes preclude definitive conclusions. Trazodone (-1.6; 95% CrI: -2.7 to -0.41) and diphenhydramine (-1.4; 95% CrI: -2.5 to -0.20) are the two treatments that showed an efficacy superior to placebo in the prevention of PPD as seen by symptom severity scores. There was no publication bias, as observed by the funnel plot and Egger's regression test. Based on single small trials, trazodone and diphenhydramine showed statistically superior efficacy to placebo in preventing PPD. Safety considerations in the perinatal and breastfeeding context must be carefully evaluated before these agents are considered in clinical practice.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"444-469"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response.","authors":"Alessandro Serretti","doi":"10.9758/cpn.26.1487","DOIUrl":"10.9758/cpn.26.1487","url":null,"abstract":"<p><p>The introduction of ketamine and its S-enantiomer, esketamine, has been one of the most consequential advances in treatment-resistant depression (TRD) in recent decades, demonstrating that rapid and clinically meaningful antidepressant effects can occur within hours, even in patients who have not responded to conventional treatments. However, this advance has not resolved the clinical problem of TRD. Rather, it has shifted the field's most important unmet needs from the induction of short-term symptom improvement to the management of what follows. The central questions now concern the post-response trajectory: how durable the initial benefit is, how relapse should be prevented, how maintenance treatment should be structured and eventually tapered, whether symptomatic improvement translates into functional recovery, which patients are most likely to benefit, why clinically useful predictive biomarkers remain elusive, and what the long-term safety and abuse-liability profile of repeated glutamatergic treatment will prove to be. This clinically oriented review examines these unresolved problems in the post-ketamine era, considers whether emerging rapid-acting antidepressants may address some of them, and argues that durability, functional recovery, patient selection, long-term safety, and implementation value, rather than acute efficacy alone, should now guide research priorities and bedside decision-making in TRD.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"24 3","pages":"429-443"},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}