CNS drugs最新文献

{"title":"Efficacy and Safety of Once-Monthly Paliperidone Palmitate Long-Acting Injections in Chinese Patients with Early-, Mid-, and Late-Phase Schizophrenia: A Post-Hoc Analysis of Three Phase 4 Studies.","authors":"Qian Li, Yang Li, Yishen Yang, Jianmin Zhuo, Miaomiao Jia, Chong Ye, Tianmei Si","doi":"10.1007/s40263-025-01194-4","DOIUrl":"10.1007/s40263-025-01194-4","url":null,"abstract":"<p><strong>Background: </strong>Long-acting injectable (LAI) antipsychotics have improved treatment adherence and continuity compared with oral antipsychotics. However, evidence gaps persist in the endorsement of LAIs for early-phase schizophrenia in China. This post-hoc analysis evaluated the efficacy and safety of once-monthly paliperidone palmitate (PP1M), an LAI antipsychotic, following early-, mid-, and late-phase use in Chinese patients with schizophrenia.</p><p><strong>Methods: </strong>Data from three phase 4 studies (NCT01527305, NCT01947803, and NCT01685931) were used. Chinese patients with schizophrenia (disease duration early: ≤ 2 years; mid: > 2 to ≤ 5 years; late: > 5 years) who received 13 weeks of PP1M treatment were included. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 13, and the secondary and exploratory endpoints included change in Clinical Global Impression of Severity scale (CGI-S), PANSS responder rate relative to baseline PANSS total scores (≤ 70, 70-90 [exclusive], and ≥ 90), and treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>In total, 1053 patients (early: 383; mid: 290; late: 380) were included. Following PP1M, improvements in efficacy outcomes were observed in all phases of schizophrenia including PANSS total score from baseline to week 13 (least square [LS]-mean change early: - 31.6; mid: - 28.4; late: - 25.6; p = 0.0003 across three groups) and CGI-S (median reduction early: - 2.0; mid: - 1.0; late: - 1.0). The greatest improvements in efficacy outcomes were consistently seen in early-phase patients, indicated by differences in PANSS total score (baseline to week 13 LS-mean differences mid versus early: 3.2 [p = 0.2175], late versus mid: 2.8 [p = 0.2783], and late versus early: 6.0 [p = 0.0011]), and nominal significant differences in CGI-S (mid versus early: p = 0.0015 and late versus early: p = 0.0180). Earlier administration of PP1M results in greater efficacy outcomes regardless of the initial disease severity. For patients with a PANSS score ≤ 70 at baseline, reductions of ≥ 30% were observed in 71.4%, 60.0%, and 50.0% (p = 0.0003 across three groups), and for patients with a PANSS score ≥ 90 at baseline, reductions of ≥ 30% were observed in 76.4%, 72.5%, and 69.6% (p = 0.0003 across three groups) of patients in the early-, mid-, and late-phase, respectively. The proportion of patients experiencing ≥ 1 TEAE (early: 44.3%; mid: 38.4%; late: 39.8%) was numerically higher in the early phase. Incidences of serious TEAEs (early: 2.8%; mid: 4.0%; late: 4.2%) and TEAEs leading to death (early: 0.3%; mid: 0.0%; late: 1.6%) were observed.</p><p><strong>Conclusions: </strong>Treatment with PP1M improves efficacy outcomes in Chinese adult patients with schizophrenia. However, when PP1M was used in earlier phases of schizophrenia, consistently greater improvements in efficacy outcomes were observed compared with later phases, r","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"795-805"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Bipolar Disorder in Pregnancy and Postpartum: A Clinicians' Guide.","authors":"Veerle Bergink, Mariella Suleiman, Mary-Anne Hennen, Thalia Robakis","doi":"10.1007/s40263-025-01202-7","DOIUrl":"10.1007/s40263-025-01202-7","url":null,"abstract":"<p><p>Medication management in women with bipolar disorder (BD) in the perinatal period is challenging, given that many patients taper or stop medication during pregnancy, and the postpartum period is an extremely high-risk period for relapse. The objective of this narrative review was to investigate the perinatal efficacy as well as potential adverse effects on the child of common treatments for bipolar disorder. These treatments include lithium, lamotrigine, other antiepileptics, quetiapine, olanzapine, aripiprazole, other antipsychotics, antidepressants, benzodiazepines, Z-drugs, and other sleep medication. Despite the worldwide decline in lithium use, it remains the gold standard for acute and maintenance treatment of BD, and we continue to advise its use in women of reproductive age. In contrast, medications with a high risk for teratogenicity such as valproate and carbamazepine should be avoided in women of childbearing potential. Women with bipolar disorder are at very high risk of relapse after delivery, but this risk is more than twofold lower with adequate pharmacological prophylaxis. We advise to make a written perinatal bipolar relapse prevention plan in collaboration with the patient, family, and healthcare professionals, which includes a description of: (1) maintenance treatment during pregnancy, (2) preferred mode of delivery, (3) medication immediately after delivery and the first months postpartum for relapse prevention, (4) preferred plan for feeding (breast-feeding versus bottle-feeding), (5) strategies to assist women in ensuring adequate sleep and stable circadian rhythm in the first weeks after delivery, and (6) how to recognize the first symptoms of relapse and which intervention strategies to take.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"763-777"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Dose of Baclofen for the Treatment of Alcohol Use Disorder: A Systematic Review and Dose-Response Meta-analysis.","authors":"Kazumasa Kotake, Ryuhei So, Nozomu Hashimoto, Eriya Imai, Takao Kaneko, Masahiro Banno, Yuki Furukawa","doi":"10.1007/s40263-025-01188-2","DOIUrl":"10.1007/s40263-025-01188-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Baclofen, a traditional treatment for spasticity, is gaining interest for its use in alcohol use disorder (AUD). To assist clinicians in using baclofen for effective and safe treatment of AUD, we investigated the optimal target dosage of baclofen through a systematic review and dose-response meta-analysis.</p><p><strong>Methods: </strong>We searched Cochrane, EMBASE, MEDLINE via PubMed, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for randomized controlled trials on 1 and 2 April 2024. Inclusion criteria were patients aged ≥ 18 years diagnosed with AUD according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV-TR, or International Classification of Diseases (ICD)-10, and treated with baclofen monotherapy. Continuous outcomes-percent days abstinent, drinks per drinking day, heavy drinking days (HDDs), craving, and anxiety-were analyzed as mean or standardized mean differences. Binary outcomes-relapse and dropout, including due to adverse events-were analyzed as odds ratios. Each outcome was assessed using the Cochrane Risk of Bias 2.0 tool. A one-stage random-effects dose-response meta-analysis was performed using restricted cubic splines with fixed knots at 10%, 50%, and 90% percentiles.</p><p><strong>Results: </strong>A total of 14 trials (1344 patients) were included. Increasing the dose of baclofen up to 50-60 mg/day was associated with a higher percent days abstinent and reduced craving. However, a higher baclofen dose increases the risk of dropout due to adverse events. Commonly observed adverse events were drowsiness, sedation, somnolence and fatigue. Baclofen up to 50-60 mg/day did not significantly affect drinks per drinking day, HDDs, anxiety, relapse or dropout. Doses > 60 mg/day lacked reliable evaluation due to limited data and study heterogeneity.</p><p><strong>Conclusions: </strong>Baclofen up to 50-60 mg/day may increase percent days abstinent and reduce craving, but may increase dropout due to adverse events. Clinicians should carefully consider individual patient factors when prescribing baclofen to patients with AUD.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"651-667"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Naltrexone on Spinal and Supraspinal Pain Mechanisms and Functional Capacity in Women with Fibromyalgia: Exploratory Outcomes from the Randomized Placebo-Controlled FINAL Trial.","authors":"Karin Due Bruun, Robin Christensen, Kirstine Amris, Morten Rune Blichfeldt-Eckhardt, Lars Bye-Møller, Marius Henriksen, Tine Alkjaer, Palle Toft, Anders Holsgaard-Larsen, Henrik Bjarke Vaegter","doi":"10.1007/s40263-025-01183-7","DOIUrl":"10.1007/s40263-025-01183-7","url":null,"abstract":"<p><strong>Background: </strong>The widespread pain and muscular fatigue characteristics of fibromyalgia are believed to be mediated by central mechanisms. Low-dose naltrexone (LDN) has emerged as a new treatment option for fibromyalgia, possibly modulating central mechanisms via glial or opioid receptors.</p><p><strong>Methods: </strong>In the randomized, placebo-controlled FINAL trial, 99 women with fibromyalgia were treated with LDN or placebo for 12 weeks. In this secondary analysis, we examined the potential effects of LDN versus placebo on changes from baseline in pain tolerance, temporal summation of pain, and conditioned pain modulation (CPM) in the complete case population (45 versus 47 participants). Measures of muscular fatigue were evaluated using the 30-s chair stand test and a shoulder abduction test.</p><p><strong>Results: </strong>Of the five examined outcomes, only change in CPM showed a significant between-group difference with greater enhancement following LDN treatment (2.0 kPa; 95% confidence interval (CI) 0.4-3.7 kPa) compared with placebo. Within-group changes in CPM showed an increase of 1.2 kPa (95% CI 0.05-2.4 kPa) in the LDN group and a possible decrease of 0.8 kPa (95% CI - 1.9 to 0.4 kPa) in the placebo group.</p><p><strong>Conclusions: </strong>We found a significant between-group difference in CPM change in favor of LDN. However, this difference was partly explained by a decrease in CPM in the placebo group. Sensitivity analyses showed no association between changes in CPM and clinical pain improvement, suggesting that the group-difference in CPM is a random finding.</p><p><strong>Study registration: </strong>ClinicalTrials.gov (NCT0427877; registered on 30 January 2020).</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"685-692"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder: A 5-Year Observational Study.","authors":"Giovanni Novi, Francesca Bovis, Chiara Sciolla, Jessica Frau, Matteo Minetti, Francesca Napoli, Marika Vianello, Giacomo Greco, Elia Sechi, Andrea Bellomo, Paola Garelli, Antonio Luca Spiezia, Roberta Fantozzi, Giuseppe Schirò, Laura Ghezzi, Chiara Zecca, Elisabetta Signoriello, Laura Brambilla, Matteo Lucchini, Simona Bonavita, Irene Schiavetti, Maria Malentacchi, Eleonora Cocco, Alessandro Franceschini, Giorgia Mataluni, Matteo Gastaldi, Anna Rolando, Paolo Solla, Maria Cellerino, Gianmarco Abbadessa, Roberta Lanzillo, Alessia Di Sapio, Antonio Uccelli, Maria Pia Sormani","doi":"10.1007/s40263-025-01191-7","DOIUrl":"10.1007/s40263-025-01191-7","url":null,"abstract":"<p><strong>Background: </strong>Neuromyelitis optica spectrum disorder (NMOSD) is a severely disabling autoimmune disease that predominantly impacts the optic nerves and spinal cord. It is often linked to immunoglobulin G (IgG) antibodies targeting the aquaporin-4 water channel (AQP4-IgG). Rituximab, which depletes CD20-positive B cells, is effective in reducing the frequency of NMOSD relapses. The objective of this retrospective, 5-year observational study was to evaluate the effectiveness and safety of rituximab in patients with AQP4-IgG-positive NMOSD.</p><p><strong>Methods: </strong>We conducted a multicenter, retrospective study using prospectively collected data from 23 multiple sclerosis (MS) and NMOSD centers (22 in Italy, 1 in Switzerland). The study cohort included patients with AQP4-IgG-positive NMOSD who had completed rituximab induction therapy, with data collected up to May 2024. Two maintenance strategies were used-fixed 6-monthly infusions or reinfusions guided by flow cytometry-on the basis of CD19⁺ or CD27⁺ memory B-cell repopulation thresholds. Clinical outcomes included annualized relapse rate (ARR), time to first relapse (TTFR), and Expanded Disability Status Scale (EDSS) worsening, which was assessed both overall and between relapses to indirectly evaluate the possibility of inter-attack disability progression. Safety outcomes encompassed infusion-related reactions and adverse events.</p><p><strong>Results: </strong>A total of 138 patients were analyzed. ARR significantly decreased from 1.54 (95% confidence interval (CI) 1.34-1.75) before rituximab to 0.15 (95% CI 0.12-0.19) over the 5-year follow-up. Approximately 33% of patients experienced at least one relapse during treatment, after a median time of 5.21 months. Higher pre-rituximab relapse rates were associated with shorter TTFR. Subtle increases of 0.5-1 points in EDSS between relapses were observed in one third of patients. Mild infections were common, and 21% of patients experienced infusion-related reactions. In addition, six patients developed malignancies.</p><p><strong>Conclusions: </strong>Over 5 years, rituximab consistently reduced the incidence of relapses in patients with NMOSD, though 33% of them still experienced a relapse during this period, generally within the first 6 months of treatment. No unexpected adverse events were identified. While safety monitoring remains crucial, further studies are needed to better understand rituximab's impact on NMOSD management.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"693-705"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cenobamate: A Review in Focal-Onset Seizures.","authors":"Tina Nie, Sheridan M Hoy","doi":"10.1007/s40263-025-01178-4","DOIUrl":"10.1007/s40263-025-01178-4","url":null,"abstract":"<p><p>Cenobamate (Ontozry^®) is a once-daily oral antiseizure medication (ASM) approved in the EU for the adjunctive treatment of focal-onset seizures, with or without secondary generalisation, in adults with epilepsy that have not been adequately controlled despite previous treatment with ≥ 2 anti-epileptic drugs. In clinical studies, its short-term use significantly reduced seizure frequency and was associated with significantly higher odds of achieving a ≥ 50% reduction in seizure frequency in adults with uncontrolled focal-onset seizures despite treatment with 1-3 concomitant ASMs. Seizure freedom rates were also improved. All these benefits were sustained over up to 48 months. Cenobamate was generally well tolerated across both the short- and longer-term (up to 94 months) clinical studies, with its low starting dosage (12.5 mg/day) and slow (12-week) titration schedule appearing to result in fewer severe treatment-emergent adverse events (TEAEs) during the titration period. Somnolence, dizziness and fatigue were the most frequently reported TEAEs. The effectiveness and adverse events of cenobamate in real-world studies were consistent with those seen in the clinical studies. Thus, cenobamate continues to represent a useful adjunctive treatment option in adults with uncontrolled focal-onset seizures.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"707-719"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Escitalopram Combined with Tandospirone Citrate in Treating Patients with Vascular Depression and Chronic Insomnia: A Randomized Controlled Trial.","authors":"Hongbin Chen, Guiying Zeng, Shufang Wu, Sengpei Xie, Xinyan Chen, Weiwei Wu, Hui Chen, Ronghua Chen, Yingchun Xiao","doi":"10.1007/s40263-025-01190-8","DOIUrl":"10.1007/s40263-025-01190-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Chronic sleeplessness is a primary clinical symptom of vascular depression (VaDep). We investigated the efficacy and safety of escitalopram plus tandospirone citrate for patients with VaDep and chronic insomnia and the potential correlation of insomnia severity with neurotransmitter indexes, including serotonin (5-HT), serotonin 2C receptor (5-HT&lt;sub&gt;2C&lt;/sub&gt;R), serotonin 7 receptor (5-HT&lt;sub&gt;7&lt;/sub&gt;R) in platelets, and plasma 5-HT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This double-blind, randomized controlled study randomized patients with VaDep and chronic insomnia [Hamilton depression rating scale (HAMD) &gt; 17 points] into a monotherapy group [escitalopram (10 mg once daily) plus placebo] or combined group [escitalopram (10 mg once daily) plus tandospirone citrate (10 mg three times daily)] by using a 1:1 assignment algorithm generated by SPSS 25.0 software. The primary endpoint was the change in sleep quality from baseline to week 12, evaluated by the Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG), Epworth Sleepiness Scale, and Asen Self-Rating Insomnia Scale (AIS). Secondary outcomes were the changes in depression and anxiety assessment and the levels of peripheral blood neurotransmitters from baseline to week 12, including HAMD, the Hamilton anxiety scale (HAMA), 5-HT, 5-HT&lt;sub&gt;2C&lt;/sub&gt;R, 5-HT&lt;sub&gt;7&lt;/sub&gt;R in platelets, and plasma 5-HT. The levels of 5-HT, 5-HT&lt;sub&gt;2C&lt;/sub&gt;R, and 5-HT&lt;sub&gt;7&lt;/sub&gt;R were detected with the enzyme-linked immunosorbent assay kits. The safety assessment included the Treatment-Emergent Symptom Scale and clinical and laboratory variables. The therapeutic improvement was analyzed by a generalized estimation equation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 123 subjects (30.89% male) were included, with a mean age of 70.56 ± 6.37 (mean ± standard deviation, SD) years. In the monotherapy group, the baseline HAMD and PSQI scores (n = 61 for both) were 28.84 ± 2.49 and 14.16 ± 1.86, respectively. In the combined group, the baseline HAMD and PSQI scores (n = 62 for both) were 28.81 ± 2.51 and 14.21 ± 1.87, respectively. The HAMA and HAMD scores in both groups were significantly lower at weeks 4, 8, and 12 after treatment than before treatment (P &lt; 0.001). Compared with the monotherapy counterpart, the combined group displayed significantly lower PSQI and AIS scores at weeks 4, 8, and 12 and improved PSG sleep macrostructure at week 12, including total sleep time (TST), sleep latency, sleep efficiency, sleep maintenance rate (SMT), wake time after sleep onset, and percentage of sleep in each phase. Platelet 5-HT, plasma 5-HT, and platelet 5-HT&lt;sub&gt;7&lt;/sub&gt;R decreased in both groups at the end of weeks 4, 8, and 12 of treatment. Platelet 5-HT&lt;sub&gt;7&lt;/sub&gt;R was moderately negatively correlated with the percentage of nonrapid eye movement 3 sleep time (N3). Plasma 5-HT was moderately positively correlated with PSQI and AIS and negatively with TST, SMT, nonrapid eye moveme","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"669-683"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Frontiers: The Rise of Selective Na_V1.8 Inhibition for Pain Management.","authors":"Ali H Eid","doi":"10.1007/s40263-025-01186-4","DOIUrl":"10.1007/s40263-025-01186-4","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"633-635"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between Tranexamic Acid Use and Safety in Patients with Acute Brain Injury: A Systematic Review and Meta-analysis of Mortality and Thromboembolic Events.","authors":"Seungjoo Lee, Moinay Kim, Sae Min Kwon, Min-Yong Kwon, Chang-Hyun Kim, Nak-Hoon Son, Jae Hyun Kim","doi":"10.1007/s40263-025-01185-5","DOIUrl":"10.1007/s40263-025-01185-5","url":null,"abstract":"<p><strong>Background: </strong>Tranexamic acid (TXA) is widely used to manage acute brain injuries, including subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. Despite its common usage, there is limited evidence on its safety in these conditions. We aimed to evaluate the impact of TXA on mortality and thromboembolic events in patients with acute brain injury.</p><p><strong>Methods: </strong>A systematic search of MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted from inception to May 2024. We included randomized controlled trials (RCTs) comparing TXA with placebo in patients aged 15 years or older with confirmed acute brain injury. Two reviewers independently assessed study quality using the revised Cochrane Risk of Bias tool and extracted data on patient demographics, intervention details, and outcomes, including mortality, thromboembolic events, and seizures. Meta-analyses were performed using random effects models.</p><p><strong>Results: </strong>Twenty-five RCTs with 16,677 participants (8584 TXA, 8093 control) were included. The relative risk (RR) for overall mortality was 0.96 (95% confidence interval (CI) 0.91-1.03, p = 0.2433), indicating a nonsignificant difference between the groups, with no substantial heterogeneity (I² = 0% [0-45%]). Additionally, no significant differences were observed in 30-, 90-, or 180-day mortality. The RR for total thromboembolic events was 1.11 (95% CI 0.97-1.28, p = 0.1236), indicating a nonsignificant difference between the groups, with low heterogeneity (I² = 15% [0-51%]). Similarly, no significant differences were observed in the incidences of deep vein thrombosis or pulmonary embolism, ischemic stroke or transient ischemic attack, acute coronary syndrome or myocardial infarction, or seizures. However, the administration of TXA for more than 1 day was associated with a significant increase in thromboembolic events (RR 1.22, 95% CI 1.03-1.44). Administering TXA beyond 8 h of injury was also associated with a significant increase in thromboembolic events (RR 1.16, 95% CI 1.02-1.33).</p><p><strong>Conclusions: </strong>TXA administration does not significantly affect overall mortality or increase the risk of thromboembolic events in patients with acute brain injuries. However, prolonged use or delayed administration may be associated with an increased risk of thromboembolic events. These findings highlight the need for careful consideration of the duration and timing of TXA administration in clinical practice.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"637-650"},"PeriodicalIF":7.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolution of Anti-CD20 Treatment for Multiple Sclerosis: Optimization of Antibody Characteristics and Function.","authors":"Bruce A C Cree, Joseph R Berger, Benjamin Greenberg","doi":"10.1007/s40263-025-01182-8","DOIUrl":"10.1007/s40263-025-01182-8","url":null,"abstract":"<p><p>B-cell depletion with CD20-targeted agents is commonly used for treatment of multiple sclerosis (MS), other autoimmune diseases, and certain hematologic malignancies. Initial apparent success with rituximab in MS and neuromyelitis optica spurred development of the anti-CD20 monoclonal antibody (mAb) therapies ocrelizumab, ofatumumab, and ublituximab as well as the anti-CD19 mAb inebilizumab. While each are effective at targeting and depleting B cells, structural differences translate into different mechanisms of action affecting maintenance of B-cell depletion and safety and tolerability. Although the anti-CD20 mAbs differ in degree of human versus mouse sequences as well as target CD20 epitope, these properties do not appear to substantially affect activity or tolerability. In contrast, an antibody-dependent cell-mediated cytotoxicity (ADCC) versus a complement-dependent cytotoxicity mechanism of action as well as subcutaneous versus intravenous administration may provide improved tolerability. Glycoengineering of the mAbs ublituximab and inebilizumab enhances ADCC and can overcome the reduced responses to mAb-mediated B-cell depletion associated with certain genetic polymorphisms. Other strategies for therapeutic targeting of CD20, including brain shuttle antibodies (e.g., RO7121932), bispecific antibodies, chimeric antigen receptor T-cell therapies, and antibody-drug conjugates, are in active clinical development and may be future treatment approaches in MS and other B-cell-mediated autoimmune diseases.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"545-564"},"PeriodicalIF":7.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}