CNS drugs最新文献

{"title":"Comparative Effectiveness of Different Opioid Regimens, in Daily Dose or Treatment Duration, Prescribed at Surgical Discharge: a Systematic Review and Meta-Analysis.","authors":"Masoud Jamshidi, Caitlin M P Jones, Aili V Langford, Asad E Patanwala, Chang Liu, Ian A Harris, Janney Wale, Mark Horsley, Sam Adie, Deanne E Jenkin, Chung-Wei Christine Lin","doi":"10.1007/s40263-025-01165-9","DOIUrl":"10.1007/s40263-025-01165-9","url":null,"abstract":"<p><strong>Background: </strong>Opioids are prescribed for postsurgical pain management, but a balance between achieving adequate pain control and minimising opioid-related harm is required. This study aimed to investigate the effectiveness of different opioid regimens, in daily dose or treatment duration, prescribed at surgical discharge.</p><p><strong>Methods: </strong>A systematic search of MEDLINE, EMBASE, CENTRAL, and ICTRP was performed from inception to 12 January 2025. Randomised controlled trials (RCTs) and non-RCTs comparing different daily doses or treatment durations of opioid analgesics were included. All surgeries were included, except those related to cancer treatment or palliative care. Eligible populations were adults (≥ 18 years) or individuals classified as adults according to the criteria of the respective studies. Data were extracted at immediate-term (≤ 3 days), short-term (> 3 to ≤ 7 days), medium-term (> 7 to ≤ 30 days), and long-term (> 30 days). Data from RCTs were pooled using a random-effects model. Risk of bias was assessed. Certainty of evidence from RCTs was evaluated with Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). The primary outcome was pain intensity. Adverse events were also measured.</p><p><strong>Results: </strong>A total of 8432 records were identified. In total, 12 RCTs with 7128 patients and 24 non-RCTs with 118,849 patients were included. Studies included orthopaedic, gynaecology and obstetric surgeries, ranging from minor to major procedures. Higher-doses of opioids were more effective than lower-doses in reducing immediate pain intensity (mean difference (MD) 4.36, 95% confidence interval (CI) 0.50-8.23, n = 364, three studies, I² = 0%, high certainty). No difference in pain was found between higher-doses and lower-doses at other time points (moderate to high certainty). Longer-durations of opioid treatment showed no difference in pain at any time point (low to moderate certainty). More adverse events were reported with higher doses of opioids.</p><p><strong>Conclusions: </strong>Higher-dose opioids provide a slight reduction in immediate post-discharge pain intensity but may lead to more adverse events. Longer durations of opioid treatment are probably not more effective in reducing pain than shorter treatment durations. Our findings suggest that clinicians may choose to prescribe lower doses of opioids or shorter durations of opioids without compromising pain control, even for major surgery.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"345-360"},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584911","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":"Maintaining Mobility and Balance in Multiple Sclerosis: A Systematic Review Examining Potential Impact of Symptomatic Pharmacotherapy.","authors":"Alyssa A Jones, Rudri Purohit, Tanvi Bhatt, Robert W Motl","doi":"10.1007/s40263-025-01159-7","DOIUrl":"10.1007/s40263-025-01159-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mobility disability (MD) manifests as walking dysfunction and postural instability in more than 90% of people with multiple sclerosis (MS) within 10 years of disease onset. Disease-modifying pharmacotherapies reduce rates of relapses and new lesions and slow disease progression, but ongoing decline in MD can persist or result from secondary, symptomatic pharmacotherapies. This systematic review focuses on symptomatic pharmacotherapies that potentially impact markers of MD in MS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed/Medline, Google Scholar, and Scopus were searched between January 1990 and December 2024. Eligible studies were included on the basis of the following criteria: (1) randomized, placebo-controlled trials (RCTs); (2) confirmed MS diagnosis; (3) one MD-related outcome; and (4) one symptomatic pharmacotherapy; OR (5) multiple doses of a symptomatic pharmacotherapy. Results were uploaded to Rayyan: Intelligent Systematic Review software and screened by two blinded reviewers for eligibility. Risk of bias was assessed using the PEDRo Scale for quality assessment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;This review included 23 RCTs (all RCTs scored good-to-excellent on PEDRo Scale); 13 RCTs examined fampridine (4-aminopyridine) for its direct effects on MD, and 10 RCTs assessed indirect effects of symptomatic pharmacotherapies, including cannabinoids (n = 9), and baclofen (n = 1) on MD. The MD outcomes included gait (25-foot walk [T25FW], kinetics, and kinematics), community mobility (12-item MS Walking Scale [MSWS-12]), endurance (6-min walk [6MW]), balance (Berg Balance Scale [BBS], Dynamic Gait Index [DGI], Six-Spot Step Test, posturography, and falls), and functional mobility (Timed Up and Go [TUG] and 5 Times Sit-to-Stand [5STS]). Fampridine significantly improved gait (T25FW, MSWS-12), endurance (6MW), and functional mobility (5STS, TUG), with the largest effect on gait speed; changes in balance were inconclusive. Indirect pharmacotherapies, specifically cannabinoids mainly reduced spasticity (Modified Ashworth Scale, nine out of nine studies), but rarely improved pain (Numerical Rating Scale, two out of nine studies) or MD outcomes (two out of nine studies). Both direct and indirect pharmacotherapies resulted in adverse effects, notably dizziness (n = 366), urinary tract infection (n = 216), and nausea (n = 150), potentially impacting MD in MS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Fampridine may improve gait and functional mobility in MS, but its effect on balance requires further investigation in RCTs. Cannabinoids and baclofen may alleviate spasticity and pain, but seemingly have limited secondary effect on markers of MD, such as gait and postural stability. Clinicians should consider the impact of symptomatic pharmacotherapies on MD in MS, including potential side effects. Future research should explore integrating rehabilitation (e.g., balance training) with symptomatic pharmacotherapies, as this might enhan","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"361-382"},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424867","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":"MDMA-Assisted Therapy for Post-Traumatic Stress Disorder: Regulatory Challenges and a Path Forward.","authors":"Balwinder Singh","doi":"10.1007/s40263-025-01162-y","DOIUrl":"10.1007/s40263-025-01162-y","url":null,"abstract":"<p><p>Trauma is prevalent, with lifetime estimates of traumatic exposure ranging from 70% for a single event to 31% for multiple events. While many recover, a subset develop post-traumatic stress disorder (PTSD), a debilitating condition characterized by distressing memories, avoidance behaviors, hyperarousal, and mood disturbances. The National Comorbidity Survey reports a lifetime PTSD prevalence of 6.8%, with higher rates among women and veterans. PTSD is strongly associated with suicidality, depression, and substance use, and its chronic nature can cause significant functional impairment. Despite extensive research, only two US Food and Drug Administration (FDA)-approved medications, the selective serotonin reuptake inhibitors paroxetine and sertraline, are available for PTSD. Psychotherapy, including trauma-focused cognitive behavioral therapy, prolonged exposure therapy, and eye movement desensitization and reprocessing (EMDR), has shown efficacy. Recent interest has grown in using psychedelics and entactogens such as 3,4-methylenedioxymethamphetamine (MDMA) for PTSD. Early-phase clinical trials of MDMA-assisted therapy (MDMA-AT) showed promising results, leading the FDA to grant breakthrough therapy status to MDMA-AT in 2017. Phase 3 randomized controlled trials demonstrated significant reductions in PTSD symptoms, with nearly 70% of participants no longer meeting diagnostic criteria. However, in 2024, the FDA voted against MDMA approval, citing concerns about trial design (including blinding failure and lack of certain safety assessments including QT prolongation and abuse liability assessments), as well as concerns about allegations of potential misconduct. Ongoing research must address key challenges, including blinding, long-term safety, and variability in psychotherapy, to better understand the therapeutic potential of MDMA in PTSD treatment. The FDA's recent guidance on psychedelic trials provides a framework for future research. The objective of this article is to explore the potential of MDMA-AT in PTSD treatment, evaluate regulatory challenges following the FDA's recent decision, and highlight the need for ongoing research to address safety, efficacy, and therapeutic implementation.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"339-343"},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424871","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":"Cardiovascular Effects of Antiseizure Medications for Epilepsy.","authors":"Maromi Nei, Jeremy Ho, Reginald T Ho","doi":"10.1007/s40263-025-01163-x","DOIUrl":"10.1007/s40263-025-01163-x","url":null,"abstract":"<p><p>Antiseizure medications (ASMs) are the primary treatment for epilepsy. However, adverse cardiac effects of ASMs can occur, related to their effects on lipid metabolism, raising ischemic heart disease risk; or specific actions on cardiac ion channels, increasing cardiac arrhythmia risk. Select ASMs, particularly enzyme inducers used at higher doses or for longer durations, can adversely affect lipids or cause metabolic changes, and thereby increase the risk for ischemic heart disease. These metabolic and potentially proarrhythmic actions may contribute to the increased cardiovascular morbidity and mortality that occur in epilepsy. Many ASMs block sodium channels or affect the QT interval, which can lead to proarrhythmia, particularly when used in combination with other medications or given to vulnerable populations. While ASMs are rarely reported to cause cardiac arrhythmias directly, population data raise concerns that cardiac arrhythmias and sudden cardiac death may be more common in epilepsy, and that sodium channel blocking ASMs in particular, might contribute. It is also possible that some cases of sudden cardiac death could be misclassified as sudden unexpected death in epilepsy (SUDEP), leading to an underestimation of the cardiovascular risk in this population. Cardiovascular risk factors, such as smoking and a sedentary lifestyle, are also associated with epilepsy, and should also be addressed. This summary is a narrative review of the literature, clarifies which ASMs tend to have more cardiovascular effects, and provides practical suggestions for medication management and monitoring from neurology and cardiology perspectives.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"383-401"},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413627","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":"Treatment De-escalation in Relapsing-Remitting Multiple Sclerosis: An Observational Study.","authors":"Jannis Müller, Sifat Sharmin, Johannes Lorscheider, Dana Horakova, Eva Kubala Havrdova, Sara Eichau, Francesco Patti, Pierre Grammond, Katherine Buzzard, Olga Skibina, Alexandre Prat, Marc Girard, Francois Grand'Maison, Raed Alroughani, Jeannette Lechner-Scott, Daniele Spitaleri, Michael Barnett, Elisabetta Cartechini, Maria Jose Sa, Oliver Gerlach, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, Tamara Castillo-Triviño, Bassem Yamout, Samia J Khoury, Özgür Yaldizli, Tobias Derfuss, Cristina Granziera, Jens Kuhle, Ludwig Kappos, Izanne Roos, Tomas Kalincik","doi":"10.1007/s40263-025-01164-w","DOIUrl":"10.1007/s40263-025-01164-w","url":null,"abstract":"<p><strong>Background: </strong>In relapsing-remitting multiple sclerosis (RRMS), extended exposure to high-efficacy disease modifying therapy may increase the risk of side effects, compromise treatment adherence, and inflate medical costs. Treatment de-escalation, here defined as a switch to a lower efficacy therapy, is often considered by patients and physicians, but evidence to guide such decisions is scarce. In this study, we aimed to compare clinical outcomes between patients who de-escalated therapy versus those who continued their therapy.</p><p><strong>Methods: </strong>In this retrospective analysis of data from an observational, longitudinal cohort of 87,239 patients with multiple sclerosis (MS) from 186 centers across 43 countries, we matched treatment episodes of adult patients with RRMS who underwent treatment de-escalation from either high- to medium-, high- to low-, or medium- to low-efficacy therapy with counterparts that continued their treatment, using propensity score matching and incorporating 11 variables. Relapses and 6-month confirmed disability worsening were assessed using proportional and cumulative hazard models.</p><p><strong>Results: </strong>Matching resulted in 876 pairs (de-escalators: 73% females, median [interquartile range], age 40.2 years [33.6, 48.8], Expanded Disability Status Scale [EDSS] 2.5 [1.5, 4.0]; non-de-escalators: 73% females, age 40.8 years [35.5, 47.9], and EDSS 2.5 [1.5, 4.0]), with a median follow-up of 4.8 years (IQR 3.0, 6.8). Patients who underwent de-escalation faced an increased hazard of future relapses (hazard ratio 2.36 and 95% confidence intervals [CI] [1.79-3.11], p < 0.001), which was confirmed when considering recurrent relapses (2.43 [1.97-3.00], p < 0.001). It was also consistent across subgroups stratified by age, sex, disability, disease duration, and time since last relapse.</p><p><strong>Conclusions: </strong>On the basis of this observational analysis, de-escalation may not be recommended as a universal treatment strategy in RRMS. The decision to de-escalate should be considered on an individual basis, as its safety is not clearly guided by specific patient or disease characteristics evaluated in this study.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"403-416"},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425050","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":"Disparities in Access to Reperfusion Therapy for Acute Ischemic Stroke (DARTS): A Comprehensive Meta-Analysis of Ethnicity, Socioeconomic Status, and Geographical Factors.","authors":"Raisa Biswas, Tissa Wijeratne, Kamil Zelenak, Bella B Huasen, Marta Iacobucci, Murray C Killingsworth, Roy G Beran, Mehari Gebreyohanns, Alakendu Sekhar, Dheeraj Khurana, Thanh N Nguyen, Pascal M Jabbour, Sonu M M Bhaskar","doi":"10.1007/s40263-025-01161-z","DOIUrl":"10.1007/s40263-025-01161-z","url":null,"abstract":"<p><strong>Background: </strong>Reperfusion therapies, such as intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are crucial for improving outcomes in patients with acute ischemic stroke (AIS). However, access to these treatments can vary significantly due to ethnicity, socioeconomic status (SES), and geographical location, impacting patient outcomes.</p><p><strong>Objectives: </strong>The Disparities in Access to Reperfusion Therapy for Acute Ischemic Stroke (DARTS) study aims to systematically assess disparities in access to IVT and EVT on the basis of ethnicity, SES, and geographical location.</p><p><strong>Methods: </strong>A comprehensive meta-analysis was conducted, incorporating data from 38 studies involving 5,256,531 patients with AIS. The analysis evaluated IVT and EVT utilization rates across ethnic groups, SES levels, and geographical locations.</p><p><strong>Results: </strong>The findings reveal substantial disparities in access to reperfusion therapies. IVT and EVT utilization rates varied significantly by ethnicity (9% ethnic, 11% non-ethnic for IVT; 7% ethnic, 6% non-ethnic for EVT), SES (13% low SES, 16% high SES for IVT; 7% low SES, 10% high SES for EVT), and geography (9% rural, 12% urban for IVT; 1% rural, 4% urban for EVT). Black patients had significantly lower odds of receiving IVT (OR 0.69, p = 0.001) and EVT (OR 0.87, p = 0.005) compared with white patients. Similarly, patients with low SES and those from rural areas faced reduced odds of receiving IVT (OR 0.74, p < 0.001; OR 0.72, p = 0.002) and EVT (OR 0.74, p < 0.001; OR 0.39, p < 0.001). Rural patients also had significantly lower odds of timely hospital arrival (p < 0.001), posing a barrier to accessing reperfusion therapies.</p><p><strong>Conclusions: </strong>The DARTS study (and this meta-analysis) reveals significant access disparities in AIS treatment related to ethnicity, geography, and SES, particularly affecting Black communities, low SES individuals, and rural populations. Despite advances in reperfusion therapies, suboptimal implementation rates persist. To address these issues, we recommend the EQUITY framework: Educate, Ensure Quality, provide Universal Access, Implement Inclusive Policy Reforms, Enhance Timely Data Collection, and Yield Culturally Sensitive Care Practices. Adopting these recommendations will improve access, reduce disparities, and enhance stroke management and outcomes globally. Equitable access is essential for all eligible patients to fully benefit from reperfusion treatments.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"417-442"},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424853","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":"Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy, Safety and Tolerability of Modified-Release Methylphenidate (MPH-MR) in Chinese Children and Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD).","authors":"Yi Zheng, Huaqing Liu, Xiuxia Wang, Haibo Li, Michaela Ruhmann, Anke Mayer, Oliver Dangel, Richard Ammer","doi":"10.1007/s40263-024-01136-6","DOIUrl":"10.1007/s40263-024-01136-6","url":null,"abstract":"<p><strong>Background and objectives: </strong>The efficacy and safety of modified-release methylphenidate (MPH-MR) in the treatment of attention-deficit/hyperactivity disorder (ADHD) have been shown in both pediatric and adult Caucasian patients. The objective of this study was to assess the efficacy and safety of MPH-MR in Chinese children and adolescents with ADHD.</p><p><strong>Methods: </strong>MICCA was a randomized, double-blind, placebo-controlled trial conducted at 19 sites in China from September 2018 to July 2021. The study enrolled children and adolescents aged 6 to < 18 years with a primary diagnosis of ADHD according to the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5). Patients were randomized 1:1 to once-daily MPH-MR (10-60 mg) or placebo. The study included an up-titration phase of up to 5 weeks and a dose maintenance phase of 4 weeks. The primary efficacy endpoint was the change in the ADHD Rating Scale-IV (ADHD-RS-IV) total score from baseline to the end of the maintenance phase (EoM). Secondary endpoints included the change from baseline to EoM in Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) total score, and Clinical Global Impression-Improvement (CGI-I) scores at EoM. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.</p><p><strong>Results: </strong>A total of 221 patients were randomized (MPH-MR: n = 110; placebo: n = 111). The change in the ADHD-RS-IV total score from baseline to EoM was significantly greater for MPH-MR versus placebo, with a least squares (LS) mean (95% confidence interval [CI]) treatment difference of - 4.6 (- 6.92, - 2.30) (p < 0.001). The mean (95% CI) treatment difference for the WFIRS-P total score change from baseline to EoM also significantly favored MPH-MR over placebo (- 6.46 [- 10.57, - 2.34]; p = 0.002). The CGI-I score at EoM was significantly lower in the MPH-MR group compared to the placebo group (2.2 vs 2.5; p = 0.002). Treatment-emergent adverse events were reported for 74 (67.3%) patients in the MPH-MR group and 55 (49.1%) patients in the placebo group. Most TEAEs were mild to moderate in severity. The most common TEAEs for MPH-MR were decreased appetite, nausea and upper respiratory tract infection. Treatment-emergent adverse events leading to study drug discontinuation/study withdrawal were reported in 4 (3.6%) patients in the MPH-MR group and 1 (0.9%) patient in the placebo group. No clinically relevant changes in vital signs were observed during the study.</p><p><strong>Conclusions: </strong>Modified-release methylphenidate was superior to placebo in improving ADHD symptoms and functioning in Chinese pediatric patients with ADHD. Modified-release methylphenidate had a good safety and tolerability profile. Trial Registration http://www.chinadrugtrials.org.cn/ Identifier: CTR20180056 (registered on 21 May 2018).</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"289-304"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817434","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":"Comment on: \"A Prospective Longitudinal Study of the Effects of Eslicarbazepine Acetate Treatment on Bone Density and Metabolism in Patients with Focal‑Onset Epilepsy\".","authors":"Zhongxing Liu, Mengzhe Tian, Lincheng Duan","doi":"10.1007/s40263-025-01157-9","DOIUrl":"10.1007/s40263-025-01157-9","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"333-334"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064303","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 of Once-Nightly Sodium Oxybate in Patients with Narcolepsy: Post Hoc Analyses of Sensitivity, Effect Size, and Numbers Needed to Treat from the Phase 3 REST-ON Trial.","authors":"Thomas Roth, Michael J Thorpy, Clete A Kushida, Jennifer Gudeman","doi":"10.1007/s40263-025-01160-0","DOIUrl":"10.1007/s40263-025-01160-0","url":null,"abstract":"<p><strong>Background: </strong>Once-nightly sodium oxybate (ON-SXB; LUMRYZ™; FT218) treatment significantly improved the coprimary endpoints of mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and number of weekly cataplexy episodes versus placebo in a randomized, placebo-controlled trial (REST-ON). The objective of these post hoc sensitivity analyses was to evaluate the robustness of treatment with ON-SXB, while accounting for missing participant data. Number needed to treat (NNT) and effect size analyses were conducted to quantify the treatment benefits.</p><p><strong>Methods: </strong>Participants ≥ 16 years of age with narcolepsy type 1 or 2 were randomized 1:1 to receive ON-SXB (4.5 g [week 1]; 6 g [weeks 2-3]; 7.5 g [weeks 4-8]; or 9 g [weeks 9-13]) or placebo. Sensitivity analyses included completer population, placebo-based multiple imputation (MI) with a missing-not-at-random assumption, analysis of covariance (ANCOVA), and tipping-point-based MI of worsening values until P > 0.05. Mean differences and P-values were calculated for the MWT and number of cataplexy episodes. For CGI-I, odds ratios and P-values were calculated for completers; mean differences (1-7 points; lower values indicate greater improvement) and P-values were calculated using ANCOVA. Effect sizes were calculated using Cohen's d; NNTs were calculated as the inverse of the absolute risk reduction.</p><p><strong>Results: </strong>In the completer population (ON-SXB, n = 69; placebo, n = 79), all ON-SXB doses demonstrated significant improvements versus placebo for all coprimary endpoints (P < 0.001). All ON-SXB doses demonstrated significant improvements (P < 0.001) versus placebo for all coprimary endpoints when missing values in both treatment arms were imputed from observed values in the placebo arm (i.e., missing data were replaced with placebo data) and when analyzed using ANCOVA. Tipping-point-based analysis on the change from baseline in mean sleep latency on the MWT demonstrated that implausible or nearly implausible baseline MWT assumptions were needed to render the differences between ON-SXB and placebo no longer statistically significant. All doses of ON-SXB had NNTs of three and effect sizes of 0.7-0.9 for MWT response. For the response in terms of number of cataplexy episodes, NNT was six for the 6 g dose and three for the 7.5 g and 9 g doses; the effect sizes were between -0.7 and -0.8. For the Epworth Sleepiness Scale (ESS) response, NNTs ranged from three to six, with a dose-response effect. Effect sizes were between -0.5 and -0.7 for all doses.</p><p><strong>Conclusions: </strong>These post hoc results demonstrate the robustness of the REST-ON clinical trial efficacy data.</p><p><strong>Clinical trial id: </strong>NCT02720744.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"61-70"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669414","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":"Targeting Kv7 Potassium Channels for Epilepsy.","authors":"Emilio Perucca, Maurizio Taglialatela","doi":"10.1007/s40263-024-01155-3","DOIUrl":"10.1007/s40263-024-01155-3","url":null,"abstract":"<p><p>Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.3 channels, play a critical role in modulating susceptibility to seizures, and mutations in genes that encode these channels cause heterogeneous epilepsy phenotypes. On the basis of this evidence, activation of Kv7.2 and Kv.7.3 channels has long been considered an attractive target in the search for novel antiseizure medications. Ezogabine (retigabine), the first Kv7.2/3 activator introduced in 2011 for the treatment of focal seizures, was withdrawn from the market in 2017 due to declining use after discovery of its association with pigmentation changes in the retina, skin, and mucosae. A novel formulation of ezogabine for pediatric use (XEN496) has been recently investigated in children with KCNQ2-related developmental and epileptic encephalopathy, but the trial was terminated prematurely for reasons unrelated to safety. Among novel Kv7.2/3 openers in clinical development, azetukalner has shown dose-dependent efficacy against drug-resistant focal seizures with a good tolerability profile and no evidence of pigmentation-related adverse effects in early clinical studies, and it is now under investigation in phase III trials for the treatment of focal seizures, generalized tonic-clonic seizures, and major depressive disorder. Another Kv7.2/3 activator, BHV-7000, has completed phase I studies in healthy subjects, with excellent tolerability at plasma drug concentrations that exceed the median effective concentrations in a preclinical model of anticonvulsant activity, but no efficacy data in patients with epilepsy are available to date. Among other Kv7.2/3 activators in clinical development as potential antiseizure medications, pynegabine and CB-003 have completed phase I safety and pharmacokinetic studies, but results have not been yet reported. Overall, interest in targeting Kv7 channels for the treatment of epilepsy and for other indications remains strong. Future breakthroughs in this area could come from exploitation of mechanistic differences in the action of Kv7 activators, and from the development of molecules that combine Kv7 activation with other mechanisms of action.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"263-288"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032514","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}