The Lancet最新文献

{"title":"Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial.","authors":"J Randolph Hecht, Young Suk Park, Josep Tabernero, Myung-Ah Lee, Soohyeon Lee, Anna C Virgili, Marc Van den Eynde, Elisa Fontana, Marwan Fakih, Gholamreza Asghari, Jane So, Alexander Stein, Olivier Dubreuil, Lubomir Bodnar, Cixin Steven He, Guan Wang, Robina Smith, Cathy Eng, Anwaar Saeed","doi":"10.1016/S0140-6736(25)02025-2","DOIUrl":"10.1016/S0140-6736(25)02025-2","url":null,"abstract":"<p><strong>Background: </strong>Zanzalintinib is a multitargeted tyrosine-kinase inhibitor that, when combined with atezolizumab, showed promising antitumour activity and manageable toxicity in a phase 1 study. We aimed to compare the efficacy and safety of zanzalintinib-atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer.</p><p><strong>Methods: </strong>STELLAR-303 is a global, randomised, open-label, phase 3 trial done at 121 centres (including hospitals, academic medical centres, and specialised cancer research facilities) in 16 countries. Patients aged 18 years and older with confirmed metastatic adenocarcinoma of the colon or rectum, who had previously received standard-of-care therapy, and did not have microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumours were randomly assigned (1:1) in blocks of four to oral zanzalintinib (100 mg daily) plus intravenous atezolizumab (1200 mg every 3 weeks) or oral regorafenib (160 mg daily on days 1-21 of each 28-day cycle) using an interactive response technology system, stratified by geographical region, RAS status, and presence of liver metastases. Dual primary endpoints were overall survival in the intention-to-treat (ITT) population and in the subset of patients without liver metastases. Safety was assessed in all patients who received at least one dose of study drug. This report is based on a planned overall survival analysis (data cutoff April 30, 2025); the trial is active but not recruiting, and continues to the final overall survival analysis in the subset of patients without liver metastases. This trial is registered with ClinicalTrials.gov (NCT05425940).</p><p><strong>Findings: </strong>1325 patients were screened for eligibility; between Sept 7, 2022, and July 15, 2024, 901 patients were randomly assigned to zanzalintinib-atezolizumab (n=451) or regorafenib (n=450). 528 (59%) patients were male and 373 (41%) were female; 485 (54%) were White, 338 (38%) were Asian, 18 (2%) were Black, 24 (3%) were other races, and 36 (4%) had race not reported. At a median follow-up of 18·0 months (IQR 14·6-21·5), zanzalintinib-atezolizumab showed a significant overall survival benefit versus regorafenib in the ITT population (stratified hazard ratio [HR] 0·80 [95% CI 0·69-0·93]; p=0·0045) with a median overall survival of 10·9 months (95% CI 9·9-12·1) versus 9·4 months (8·5-10·2). At the interim analysis of overall survival in the subset of patients without liver metastases, the stratified HR for zanzalintinib-atezolizumab versus regorafenib was 0·79 (95% CI 0·61-1·03); p=0·087 (median overall survival 15·9 months [95% CI 13·5-17·6] vs 12·7 months [10·9-15·5]). Grade 3 or worse treatment-related adverse events occurred in 268 (60%) of 446 patients receiving zanzalintinib-atezolizumab and 161 (37%) of 434 patients receiving regorafenib. There were five (1%) treatment-related deaths in the zanzalintinib-atezolizumab group and one (<1%) in","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2360-2370"},"PeriodicalIF":88.5,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355136","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}

{"title":"Lessons from CONCORD and VENUSCANCER: closing global gaps in cancer care for women.","authors":"Benjamin O Anderson, Catherine Duggan","doi":"10.1016/S0140-6736(25)01580-6","DOIUrl":"10.1016/S0140-6736(25)01580-6","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2298-2300"},"PeriodicalIF":88.5,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370439","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}

{"title":"Global variation in patterns of care and time to initial treatment for breast, cervical, and ovarian cancer from 2015 to 2018 (VENUSCANCER): a secondary analysis of individual records for 275 792 women from 103 population-based cancer registries in 39 countries and territories.","authors":"Claudia Allemani, Pamela Minicozzi, Bozena Morawski, Carlos A Lima, Damien Bennett, Donsuk Pongnikorn, Dafina Petrova, Kaire Innos, Fabio Girardi, Yaima Galán Alvarez, Robin Schaffar, Luigino Dal Maso, Florence Molinié, Mikhail Valkov, Karen Phillips, Sabine Siesling, Annemarie Schultz, Laetitia Daubisse-Marliac, Rafael Marcos-Gragera, Veronica Di Carlo","doi":"10.1016/S0140-6736(25)01383-2","DOIUrl":"10.1016/S0140-6736(25)01383-2","url":null,"abstract":"<p><strong>Background: </strong>Cancers of the breast, cervix, and ovary are a major public health problem worldwide. Evaluating the consistency with clinical guidelines for treatment by use of individual high-resolution data from population-based cancer registries is a powerful tool to help interpretation of global inequalities in cancer survival. The VENUSCANCER project aims to assess the worldwide variation in patterns of care and time to initial treatment for women diagnosed with one of these three common cancers.</p><p><strong>Methods: </strong>In this secondary analysis of anonymised individual records from population-based cancer registries (VENUSCANCER), 103 registries from 39 countries worldwide contributed high-resolution data for women diagnosed with cancer of the breast, cervix, or ovary for a single year of incidence during 2015-18. High-resolution data included cancer stage at diagnosis; staging procedures; tumour grade; biomarkers (ER, PR, and HER2); and the first course of each treatment modality (surgery, radiotherapy, chemotherapy, endocrine treatment, or anti-HER2 therapy) and related dates. We examined prognostic factors, key indicators of consistency with international clinical guidelines for treatment (ESMO, ASCO, and NCCN), and median time between diagnosis and treatment, by country or territory. We analysed the odds of women receiving treatment consistent with guidelines in high-income countries (HICs) and low-income and middle-income countries (LMICs), controlling for age and tumour subtype.</p><p><strong>Findings: </strong>We received 275 792 anonymised individual records for women diagnosed with a cancer of the breast (214 111 [77·6%]), cervix (44 468 [16·1%], including in situ), or ovary (17 213 [6·2%]). In HICs, early-stage, node-negative cancers comprised over 40% of breast and cervical cancers, but less than 20% of ovarian cancers. By contrast, in LMICs, these proportions were generally below 20% for all three cancers, but higher in Cuba (30% for breast), and Russia (36% for cervix and 27% for ovary). Consistency with main international guidelines was highly variable, particularly for surgery and radiotherapy in early-stage breast cancer (from 13% in Georgia to 82% in France), chemotherapy in advanced cervical cancer (from 18% in Mongolia to 90% in Canada), and surgery plus chemotherapy in metastatic ovarian cancer (from 9% in Cuba to 53% in the USA). Some type of surgery was offered to 78% of women in HICs and 56% of women in LMICs, but initial treatment that is consistent with clinical guidelines for early-stage tumours was followed more uniformly for cervical and ovarian cancer than for breast cancer. Older women (aged 70-99 years) had lower odds of receiving initial treatment consistent with clinical guidelines than women aged 50-69 years in both HICs and LMICs. The median time between diagnosis and treatment for early-stage cancers was less than 1 month in several HICs, but up to 4 months for cervical cancer in","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2325-2348"},"PeriodicalIF":88.5,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370368","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}

{"title":"Dual antiplatelet therapy after percutaneous coronary intervention according to bleeding risk (HOST-BR): an open-label, multicentre, randomised clinical trial.","authors":"Jeehoon Kang, Kyung Woo Park, Jung-Kyu Han, Doyeon Hwang, Han-Mo Yang, Sungjoon Park, Hyo-Suk Ahn, Kyung-Kuk Hwang, Byung Gyu Kim, Jin-Ok Jeong, Jong-Hwa Ahn, Jay Young Rhew, Hanbit Park, Tae Soo Kang, Jin-Sin Koh, Kyung-Taek Park, Duk Won Bang, Choong-Won Goh, Hyuck-Jun Yoon, Sang-Ho Jo, Ji Yong Jang, Young Jin Choi, Sang Rok Lee, Young-Hyo Lim, Hyo-Soo Kim","doi":"10.1016/S0140-6736(25)01571-5","DOIUrl":"10.1016/S0140-6736(25)01571-5","url":null,"abstract":"<p><strong>Background: </strong>The optimal duration of dual antiplatelet therapy (DAPT) after coronary stenting according to bleeding risk is not well established. We aimed to evaluate the optimal duration of DAPT after coronary stenting according to bleeding risk.</p><p><strong>Methods: </strong>In this open-label, multicentre, randomised clinical trial, patients aged 19 years and older who received percutaneous coronary intervention with a drug-eluting stent at 50 high-volume cardiology centres in South Korea were stratified into high bleeding risk (HBR) or non-HBR strata, according to Academic Research Consortium for High Bleeding Risk criteria. Patients in the HBR stratum were randomly assigned (1:1) to 1-month or 3-month DAPT, and those in the non-HBR stratum were randomly assigned (1:1) to 3-month or 12-month DAPT. The three coprimary endpoints were net adverse clinical events (all-cause death, myocardial infarction, stent thrombosis, stroke, or major bleeding), major adverse cardiac or cerebral events (cardiovascular death, myocardial infarction, definite or probable stent thrombosis, or ischaemic stroke), and any actionable non-surgical bleeding at 1 year after randomisation. Primary endpoints were assessed in hierarchical order in the intention-to-treat population. This study is registered with cris.nih.go.kr, KCT0005356, and ClinicalTrials.gov, NCT05631769, and is complete.</p><p><strong>Findings: </strong>From July 24, 2020, to Sept 25, 2023, 4897 patients were enrolled (1598 in the HBR stratum and 3299 in the non-HBR stratum). In the HBR stratum, 1-month compared with 3-month DAPT did not reach non-inferiority for net adverse clinical events (144 [18·4%] of 798 vs 110 [14·0%] of 800 patients; hazard ratio [HR] 1·337 [95% CI 1·043-1·713]; p=0·82 for non-inferiority). Major adverse cardiac or cerebral events occurred in 74 (9·8%) patients in the 1-month DAPT group and 44 (5·8%) in the 3-month group; bleeding occurred in 105 (13·8%) patients in the 1-month group and 122 (15·8%) in the 3-month group. In the non-HBR stratum, 3-month was non-inferior to 12-month DAPT regarding net adverse clinical events (47 [2·9%] of 1649 vs 72 [4·4%] of 1650 patients; HR 0·657 [0·455-0·949]; p<0·0001 for non-inferiority) and major adverse cardiac or cerebral events (36 [2·2%] vs 37 [2·3%]; HR 0·984 [0·622-1·558]; p=0·0082 for non-inferiority), and superior for bleeding (120 [7·4%] vs 190 [11·7%]; HR 0·631 [0·502-0·793]; p<0·0001).</p><p><strong>Interpretation: </strong>In east Asian patients with HBR, 1-month DAPT did not reach non-inferiority to 3-month DAPT for net adverse clinical events. In patients without HBR, 3-month DAPT was non-inferior to 12-month DAPT regarding net adverse clinical events and major adverse cardiac or cerebral events, and superior for bleeding.</p><p><strong>Funding: </strong>Medtronic and Abbott.</p>","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":"406 10516","pages":"2244-2256"},"PeriodicalIF":88.5,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113590","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}

{"title":"Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial.","authors":"John Deanfield, A Michael Lincoff, Steven E Kahn, Scott S Emerson, Ildiko Lingvay, Benjamin M Scirica, Jorge Plutzky, Robert F Kushner, Helen M Colhoun, G Kees Hovingh, Signe Stensen, Peter E Weeke, Ole Kleist Jeppesen, Rafael Bravo, Chau-Chung Wu, Issei Komuro, Ferruccio Santini, Jøran Hjelmesæth, Miguel Urina-Triana, Silvio Buscemi, Donna H Ryan","doi":"10.1016/S0140-6736(25)01375-3","DOIUrl":"10.1016/S0140-6736(25)01375-3","url":null,"abstract":"<p><strong>Background: </strong>The SELECT trial found semaglutide reduced major adverse cardiovascular events (MACE) in patients with overweight or obesity with cardiovascular disease but without diabetes. We report a prespecified analysis of the SELECT trial on the relationships between baseline adiposity measures, treatment-induced adiposity changes, and subsequent MACE risk.</p><p><strong>Methods: </strong>Patients aged at least 45 years, with a BMI of at least 27 kg/m² were enrolled in 41 countries (804 sites) and randomised 1:1 to once-weekly semaglutide 2·4 mg or placebo. The primary outcome was time to first MACE (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Adiposity measures included weight and waist circumference. In this analysis, risk of MACE occurring after 20 weeks was assessed between patients by adiposity changes in the first 20 weeks and, in a separate analysis, all in-trial MACE were assessed between patients by adiposity changes over 104 weeks. This trial is registered with ClinicalTrials.gov, NCT03574597.</p><p><strong>Findings: </strong>Semaglutide significantly reduced MACE incidence compared with placebo among 17 604 patients enrolled in SELECT, with consistent benefits across all baseline weight and waist circumference categories. In the semaglutide group, analyses for linear trends showed lower baseline bodyweight and waist circumference were associated with lower incidence of MACE-an average 4% reduction in risk per 5 kg lower bodyweight (hazard ratio [HR] 0·96 [95% CI 0·94-0·99]; p=0·001) and per 5 cm smaller waist circumference (0·96 [0·93-0·99]; p=0·004). In the placebo group, lower baseline waist circumference (0·96 [0·94-0·99]; p=0·007), but not bodyweight (0·99 [0·97-1·01]; p=0·28), was associated with a lower MACE risk and weight loss was paradoxically associated with increased MACE risk. In those receiving semaglutide there was no linear trend linking weight loss at week 20 to subsequent MACE risk, but greater waist circumference reduction at week 20 was associated with lower subsequent MACE risk, and waist circumference reduction by week 104 was associated with lower in-trial risk of MACE. An estimated 33% of the observed benefit on MACE was mediated through waist circumference reduction (HR 0·86 [95% CI 0·77-0·97] after adjustment for time-varying changes in waist circumference).</p><p><strong>Interpretation: </strong>The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.</p><p><strong>Funding: </strong>Novo Nordisk.</p>","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2257-2268"},"PeriodicalIF":88.5,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370413","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}

{"title":"Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial.","authors":"Zhiwei Chen, Fang Yang, Zhou Jiang, Longhua Sun, Lin Wu, Zhengxiang Han, Yun Fan, Yanqiu Zhao, Xingya Li, Haipeng Xu, Xiangjiao Meng, Ying Liu, Zhiye Zhang, Hui Luo, Xuelei Ma, Xuezhen Ma, Qin Shi, Zhongmin Zhang, Runxiang Yang, Pingli Wang, Pinhua Pan, Xiaohong Ai, Jie Li, Xingxiang Pu, Zhiwu Wang, Jian Fang, Ming He, Yong He, Shuliang Guo, Juan Li, Hongbiao Wang, Junqiang Zhang, Qian Chu, Xuewen Liu, Shenpeng Ying, Hongcheng Wu, Hongmei Sun, Yinghua Ji, Ming Zhou, Chao Cao, Kejing Tang, Zhengguo Li, Dairong Li, Zhihong Zhang, Jie Li, Jianya Zhou, Hongzhong Yang, Yingying Du, Hui Yang, Jian Shi, Hualin Chen, Wenting Li, Dongmei Lu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Shun Lu","doi":"10.1016/S0140-6736(25)01848-3","DOIUrl":"10.1016/S0140-6736(25)01848-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Squamous non-small-cell lung cancer (NSCLC) is associated with worse clinical outcomes than non-squamous NSCLC, but treatment options are scarce. We aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a randomised, double-blind, phase 3 trial at 50 sites across China (HARMONi-6). Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive intravenous ivonescimab (20 mg/kg) or tislelizumab (200 mg), plus intravenous paclitaxel (175 mg/m&lt;sup&gt;2&lt;/sup&gt;) and carboplatin (area under the curve 5 mg/mL per min) once every 3 weeks for four cycles, followed by ivonescimab (20 mg/kg) or tislelizumab (200 mg) monotherapy as maintenance treatment for up to 24 months. Randomisation was stratified by disease stage (IIIB or IIIC vs IV) and PD-L1 tumour proportion score (≥1% vs &lt;1%). The primary endpoint was progression-free survival assessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients. Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment. This study is registered at ClinicalTrial.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;From Aug 17, 2023, to Jan 21, 2025, 761 patients were screened for eligibility, among whom 532 (70%) patients were enrolled and randomly assigned to receive ivonescimab plus chemotherapy (266 [50%] patients) or tislelizumab plus chemotherapy (266 [50%] patients). As of Feb 28, 2025, median follow-up time was 10·3 months (95% CI 9·5-11·0). Median progression-free survival was 11·1 months (95% CI 9·9-not evaluable) in the ivonescimab group and 6·9 months (5·8-8·6) in the tislelizumab group (hazard ratio 0·60 [95% CI 0·46-0·78]; one-sided p&lt;0·0001). The progression-free survival benefit with ivonescimab plus chemotherapy was consistent regardless of PD-L1 status. 170 (64%) patients in the ivonescimab group and 144 (54%) patients in the tislelizumab group had grade 3 or higher treatment-related adverse events, with grade 3 or higher immune-related adverse events occurring in 24 (9%) patients in the ivonescimab group and in 27 (10%) patients in the tislelizumab group. Grade 3 or higher treatment-related haemorrhage occurred in five (2%) patients in the ivonescimab group and in two (1%) patients in the tislelizumab group.&lt;/p&gt;&lt;p&gt;&lt;s","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2078-2088"},"PeriodicalIF":88.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346171","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}

{"title":"The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis.","authors":"Toby Pillinger, Atheeshaan Arumuham, Robert A McCutcheon, Enrico D'Ambrosio, Georgios Basdanis, Marco Branco, Richard Carr, Valeria Finelli, Toshi A Furukawa, Siobhan Gee, Adrian Heald, Sameer Jauhar, Zihan Ma, Valentina Mancini, Calum Moulton, Georgia Salanti, David M Taylor, Anneka Tomlinson, Allan H Young, Orestis Efthimiou, Oliver D Howes, Andrea Cipriani","doi":"10.1016/S0140-6736(25)01293-0","DOIUrl":"10.1016/S0140-6736(25)01293-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Antidepressants induce physiological alterations; however, the degree to which these occur in treatment with various antidepressants is unclear. We aimed to compare and rank antidepressants based on physiological side-effects by synthesising data from randomised controlled trials (RCTs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched MEDLINE, EMBASE, PsycINFO, ClinicalTrials.gov, and the US Food and Drug Administration (FDA) website from database inception to April 21, 2025. We included single-blinded and double-blinded RCTs comparing antidepressants and placebo in acute monotherapy of any psychiatric disorder. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in weight; total cholesterol; glucose; heart rate; systolic and diastolic blood pressure; corrected QT interval (QTc); sodium; potassium; aspartate transferase (AST); alanine transaminase (ALT); alkaline phosphatase (ALP); bilirubin; urea; and creatinine. We did meta-regressions to examine study-level associations between physiological change and age, sex, and baseline weight. We estimated the correlation between depressive symptom severity change and metabolic parameter change.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of 26 252 citations, 151 studies and 17 FDA reports met inclusion criteria. The overall sample included 58 534 participants, comparing 30 antidepressants with placebo. Median treatment duration was 8 weeks (IQR 6·0-8·5). We observed clinically significant differences between antidepressants in terms of metabolic and haemodynamic effects, including an approximate 4 kg difference in weight-change between agomelatine and maprotiline, over 21 beats-per-minute difference in heart rate change between fluvoxamine and nortriptyline, and over 11 mmHg difference in systolic blood pressure between nortriptyline and doxepin. Paroxetine, duloxetine, desvenlafaxine, and venlafaxine were associated with increases in total cholesterol and, for duloxetine, glucose concentrations, despite all drugs reducing bodyweight. There was strong evidence of duloxetine, desvenlafaxine, and levomilnacipran increasing AST, ALT, and ALP concentrations, although the magnitudes of these alterations were not considered clinically significant. We did not find strong evidence of any antidepressant affecting QTc, or concentrations of sodium, potassium, urea, and creatinine to a clinically significant extent. Higher baseline bodyweight was associated with larger antidepressant-induced increases in systolic blood pressure, ALT, and AST, and higher baseline age was associated with larger antidepressant-induced increases in glucose. We did not observe an association between changes in depressive symptoms and metabolic disturbance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to ref","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2063-2077"},"PeriodicalIF":88.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367701","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}

{"title":"Department of Error.","authors":"","doi":"10.1016/S0140-6736(25)02154-3","DOIUrl":"10.1016/S0140-6736(25)02154-3","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2062"},"PeriodicalIF":88.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367699","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}

{"title":"Department of Error.","authors":"","doi":"10.1016/S0140-6736(25)02125-7","DOIUrl":"https://doi.org/10.1016/S0140-6736(25)02125-7","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":"406 10514","pages":"1952"},"PeriodicalIF":88.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370408","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}

{"title":"Offline: \"People have died\".","authors":"Richard Horton","doi":"10.1016/S0140-6736(25)02151-8","DOIUrl":"https://doi.org/10.1016/S0140-6736(25)02151-8","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":"406 10514","pages":"1934"},"PeriodicalIF":88.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370428","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}