CNS drugs最新文献

{"title":"Tofersen: A Review in Amyotrophic Lateral Sclerosis Associated with SOD1 Mutations.","authors":"Aisling McGuigan, Hannah A Blair","doi":"10.1007/s40263-025-01204-5","DOIUrl":"https://doi.org/10.1007/s40263-025-01204-5","url":null,"abstract":"<p><p>Tofersen (QALSODY^®) is the first drug approved for the treatment of amyotrophic lateral sclerosis (ALS) associated with superoxide dismutase 1 (SOD1) mutations. Tofersen is an antisense oligonucleotide that induces SOD1 mRNA degradation. In the 28-week, placebo-controlled, multinational, phase III VALOR trial, intrathecally administered tofersen reduced plasma concentrations of neurofilament proteins (biomarker for neuro-axonal injury) and total SOD1 protein in cerebrospinal fluid in patients with SOD1 mutation-associated ALS. These reductions were sustained in a long-term, open-label extension study. The decline in functional outcomes was not significantly reduced with tofersen treatment compared with placebo in the 28-week phase III trial, although in the longer-term open-label study, early tofersen initiation was associated with slowed functional decline versus delayed tofersen initiation. Tofersen had an acceptable tolerability profile in clinical trials with a favourable benefit-to-risk balance. In summary, tofersen is a new disease-modifying therapy for patients with ALS attributed to an SOD1 mutation, offering reductions in levels of a biomarker associated with neurodegeneration and disease progression, with an acceptable tolerability profile.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607674","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":"Psychedelics for Alcohol Use Disorder: A Narrative Review with Candidate Mechanisms of Action.","authors":"Eric A Miller, Christy Capone, Erica Eaton, Robert M Swift, Carolina L Haass-Koffler","doi":"10.1007/s40263-025-01199-z","DOIUrl":"https://doi.org/10.1007/s40263-025-01199-z","url":null,"abstract":"<p><p>Psychedelics have been studied since the 1950s as a potential treatment for alcohol use disorder (AUD), with over a dozen clinical trials of lysergic acid diethylamide (LSD), and several contemporary trials of psilocybin and ayahuasca for this indication. Herein, we characterize foundational studies from the 1950s to the present, with emphasis on key design factors that varied considerably between published studies. Critically, those design factors include pharmacological factors, such as presence or absence of a placebo control and the nature of the placebo (e.g., ephedrine, dextroamphetamine, diphenhydramine, or low-dose LSD), and non-pharmacological factors, such as the treatment setting and the presence or absence of psychotherapy. We found that observational studies nearly uniformly show promising results, but trials in which psychedelics were tested against placebo or standard of care control groups have been more inconsistent in both outcomes and methodologies. Given the inconsistency in published results, we review candidate mechanisms of action for psychedelics in the context of AUD. We take a biopsychosocial approach, reviewing mechanisms spanning several different hierarchical levels of analysis, including cellular neuroplasticity, cognitive neuroscience, subjective experience, and social connection. Taken together, this review highlights key findings on both the efficacy and potential mechanisms of psychedelics for the treatment of AUD, which could motivate future studies in this rapidly developing field.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607673","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":"Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial.","authors":"Stuart Madden, Issam Awad, Miguel A Lopez-Toledano, Leslie Morrison, Juan Gutierrez, Leock Y Ngo, Enrique Carrazana, Adrian L Rabinowicz","doi":"10.1007/s40263-025-01198-0","DOIUrl":"https://doi.org/10.1007/s40263-025-01198-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Cerebral cavernous malformations (CCMs) are vascular lesions of the brain that can lead to hemorrhage, focal neurologic deficits, and seizures. Rho-associated kinase (ROCK) overactivation plays a critical role in the development of CCMs, and a novel, selective ROCK2 inhibitor, NRL-1049, mitigated lesion burden and bleeding in mouse models of CCM. This study examined the safety, tolerability, and pharmacokinetics of NRL-1049 in healthy volunteers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this first-in-human, randomized, double-blind, single-ascending dose study, participants received a single, oral dose of NRL-1049 (25, 75, 150, or 250 mg) or placebo in a fasted state (period 1). In period 2, participants received 150 mg NRL-1049 or placebo 30 min after a standardized high-fat, high-calorie meal. Blood samples for pharmacokinetic analysis were collected pre-dose and at post-dose time points from 5 min to 48 h. Treatment-emergent adverse events (TEAEs) were recorded and pharmacokinetic parameters determined, including maximum drug concentration (C&lt;sub&gt;max&lt;/sub&gt;), time to C&lt;sub&gt;max&lt;/sub&gt; (t&lt;sub&gt;max&lt;/sub&gt;), and area under the concentration-time curve (AUC) from time 0 to last quantifiable concentration (AUC&lt;sub&gt;0-t&lt;/sub&gt;) and extrapolated to infinity (AUC&lt;sub&gt;0-∞&lt;/sub&gt;).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the 24 participants in period 1 who received NRL-1049 (fasted), 9 (37.5%) experienced ≥ 1 TEAE, with 8 (33.3%) reporting ≥ 1 treatment-related TEAE. TEAEs appeared to correlate with dose, and 150 mg was the maximum tolerated dose following single-dose administration in this study. The most common TEAEs (&gt; 5%) were dizziness (16.7%), headache (8.3%), and syncope (8.3%). In period 2 (n = 10), four (40.0%) participants who received 150 mg NRL-1049 (fed) reported ≥ 1 TEAE, and three (30.0%) reported a treatment-related TEAE. There were no reports of serious TEAEs or discontinuations due to a TEAE. NRL-1049 was rapidly absorbed in the fasted state, with median t&lt;sub&gt;max&lt;/sub&gt; ranging from 0.50 to 0.75 h. Mean C&lt;sub&gt;max&lt;/sub&gt; increased over the dose range of 25-250 mg (3.66-58.0 ng/mL). As NRL-1049 dose increased in a ratio of 1:3:6:10, mean C&lt;sub&gt;max&lt;/sub&gt; similarly increased (1:5:10:16), while AUC&lt;sub&gt;0-t&lt;/sub&gt; and AUC&lt;sub&gt;0-∞&lt;/sub&gt; increased in a greater-than-dose proportional manner (1:5:11:25 and 1:4:10:21, respectively; P &lt; 0.001). In the fed state (150 mg NRL-1049), mean C&lt;sub&gt;max&lt;/sub&gt; (18.5 ng/mL) was lower compared with the fasted state (34.9 ng/mL). For the active metabolite, NRL-2017, in the fasted state, median t&lt;sub&gt;max&lt;/sub&gt; was 0.88-1.63 h, and mean C&lt;sub&gt;max&lt;/sub&gt; increased over the dose range (54.2-1520 ng/mL). Mean C&lt;sub&gt;max&lt;/sub&gt; (1:6:14:28), AUC&lt;sub&gt;0-t&lt;/sub&gt; (1:4:7:14), and AUC&lt;sub&gt;0-∞&lt;/sub&gt; (1:3:6:13) of NRL-2017 increased in a greater-than-dose proportional manner (P &lt; 0.001). In the fed state, mean C&lt;sub&gt;max&lt;/sub&gt; was lower compared with the fasted state.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583276","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":"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":"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":"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}