CNS drugs最新文献

{"title":"Correction: Antiseizure Medications and Sudden Unexpected Death in Epilepsy: An Updated Review.","authors":"Anemoon T Bosch, Josemir W Sander, Roland D Thijs","doi":"10.1007/s40263-025-01176-6","DOIUrl":"https://doi.org/10.1007/s40263-025-01176-6","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691216","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":"Is the Effect of Intensive Antihypertensive Treatment in Acute Intracerebral Hemorrhage Dependent on Hematoma Volume? A Traditional Meta-analysis of the Effect of Antihypertensive Regimens, a Bayesian Network Meta-analysis of the Mortality of Antihypertensive Drugs and Systematic Review.","authors":"Cong Li, Lishuai Li, Zhi Li, Kunhang Li, Xin Shi, Yijun Bao","doi":"10.1007/s40263-025-01174-8","DOIUrl":"https://doi.org/10.1007/s40263-025-01174-8","url":null,"abstract":"<p><p>BACKGROUND AND OBJECTIVES: Intensive or conventional antihypertensive treatment for acute intracerebral hemorrhage is still controversial. This study aimed to compare those antihypertensive regimens and analyze the efficacy of antihypertensive drugs.</p><p><strong>Methods: </strong>Retrieval was conducted through four databases. Meta-analysis and Bayesian network meta-analysis were performed to evaluate the safety of antihypertensive treatments and the efficacy of antihypertensive drugs.</p><p><strong>Results: </strong>A total of 9271 patients were included. Intensive strategy showed an advantage in 24-h hematoma enlargement (relative risk, RR = 0.76; 95% confidence intervals, CI = 0.67-0.87; P < 0.0001) and 90-day intracranial rebleeding (RR = 0.71, 95% CI = 0.52-0.96, P = 0.03) compared with conventional strategy. Meanwhile, the 90-day renal insufficiency (RR = 2.31, 95% CI = 1.05-5.05, P = 0.04) and renal failure (RR = 2.42, 95% CI = 1.20-4.86, P = 0.01) were increased. When cerebral hematoma volume was less than 15 ml, intensive strategy had a protective effect on 24-h hematoma enlargement (RR = 0.77, 95% CI = 0.67-0.89, P = 0.0003), but it increased 90-day renal failure (RR = 2.33, 95% CI = 1.07-5.04, P = 0.03). For the volume greater than 15 ml, it enhanced 90-day functional independence (RR = 0.78, 95% CI = 0.65-0.94, P = 0.01) and decreased intracranial rebleeding (RR = 0.68, 95% CI = 0.49-0.94, P = 0.02). Labetalol was the best, with the mortality risk probability of 0.09 and the surface under the cumulative ranking curve of 0.33.</p><p><strong>Conclusions: </strong>This meta-analysis suggests that for intracerebral hematoma volume greater than 15 ml, intensive antihypertensive treatment can improve functional independence and reduce intracranial bleeding. Labetalol has the best effect among the four antihypertensive regimens studied.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669417","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":"Update on Neuroprotection after Traumatic Brain Injury.","authors":"Aaron M Cook, Morgan Michas, Blake Robbins","doi":"10.1007/s40263-025-01173-9","DOIUrl":"https://doi.org/10.1007/s40263-025-01173-9","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a prevalent cause of morbidity and mortality worldwide. A focus on neuroprotective agents to prevent the secondary injury cascade that follows moderate-to-severe TBI has informed the field greatly but has not yielded any viable therapeutic options to date. New strategies and pharmacotherapy options for neuroprotection continue to be evaluated, including tranexamic acid, progesterone, cerebrolysin, cyclosporin A, citicholine, memantine, and lactate. Biomarkers of injury that can aid in diagnosis and prognosis have also been elucidated and are incrementally being used in clinical practice. The spectrum of TBI severity has also gained increasing attention as it relates to mild TBI or concussion, blast injury, and subacute or chronic subdural hematomas. In this review, we review the pathophysiology, recent clinical trials, and future directions for acute TBI.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633657","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 Safety Profile of Pridopidine, a Novel Sigma-1 Receptor Agonist for the Treatment of Huntington's Disease.","authors":"Yigal Paul Goldberg, Leehee Navon-Perry, Andrés Cruz-Herranz, Kelly Chen, Gabriele Hecker-Barth, Katrin Spiegel, Yael Cohen, Martin Niethammer, Andrew M Tan, Henk Schuring, Michal Geva, Michael R Hayden","doi":"10.1007/s40263-025-01171-x","DOIUrl":"https://doi.org/10.1007/s40263-025-01171-x","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is a rare, fatal, chronic progressive neurodegenerative disorder with a significant unmet medical need for effective treatments. Pridopidine is a novel, first-in-class, highly selective and potent sigma-1 receptor (S1R) agonist in development for HD. Pridopidine has been extensively studied in adult HD across the full spectrum of disease severity and age ranges, and its safety profile has been characterized in approximately 1600 participants across multiple studies and a broad range of doses. The specific objective of this study was to gain an in-depth understanding of pridopidine's safety profile at the recommended human dose of 45 mg twice daily (bid) in patients with HD.</p><p><strong>Methods: </strong>An integrated safety analysis of pooled data from 1067 patients with HD enrolled in four double-blind, placebo-controlled studies was performed. The safety profile of pridopidine was compared with placebo.</p><p><strong>Results: </strong>Pridopidine was found to be generally safe and well tolerated with an adverse event (AE) profile comparable to that of placebo. Moreover, there were no significant differences observed in the safety profile of pridopidine compared with placebo when analyzed by age, sex, baseline total functional capacity (TFC), cytosine-adenine-guanine (CAG) repeat length, use of antidopaminergic medications (ADMs), and region.</p><p><strong>Conclusions: </strong>The integrated analysis replicated and corroborated the good safety profile observed in the individual studies. Despite the larger sample size, no new safety signals emerged. Long-term exposure to pridopidine, up to 6.5 years in open-label extension studies, revealed no new safety concerns, supporting its potential for long-term use in patients with HD.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584915","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":"Early High-Risk Opioid Prescribing and Persistent Opioid Use in Australian Workers with Workers' Compensation Claims for Back and Neck Musculoskeletal Disorders or Injuries: A Retrospective Cohort Study.","authors":"Yonas Getaye Tefera, Shannon Gray, Suzanne Nielsen, Michael Di Donato, Alex Collie","doi":"10.1007/s40263-025-01169-5","DOIUrl":"https://doi.org/10.1007/s40263-025-01169-5","url":null,"abstract":"<p><strong>Background: </strong>Opioid prescribing to injured workers has increased despite evidence demonstrating that risks often outweigh the benefits. High-risk prescribing and persistent opioid use are often associated with harm. However, there are limited data on what predicts early high-risk and persistent opioid prescribing in Australian workers with back and neck-related injuries or disorders.</p><p><strong>Objective: </strong>The purpose of this study was to determine the prevalence and identify determinants of early high-risk and persistent opioid prescribing in Australian workers with back and neck conditions.</p><p><strong>Methods: </strong>A retrospective cohort study was carried out with injured workers with workers' compensation claims for back and neck conditions who filled at least one opioid prescription within the first 90 days after injury from 1 January 2010 to 31 December 2019. High-risk opioid prescribing practices in the first 90 days were measured using one of four indicators of risk (high-total opioid volume on first dispensing occasion-exceeding 350 mg oral morphine equivalent in the first week, average high-dose over 90 days-higher than 50 mg oral morphine equivalent, early supply with long-acting opioids, and concurrent psychotropic prescriptions). Persistent opioid use was determined using group-based trajectory modeling over the subsequent 1-year. Multivariable logistic regression was used to identify predictors of high-risk opioid prescribing in the first 90 days and persistent opioid use in the subsequent year.</p><p><strong>Results: </strong>A total of 6278 injured workers prescribed opioids were included. At least one indicator of high-risk opioid prescribing was identified in 67.1% of the sample in the first 3 months. Persistent opioid use was identified in 22.8% of the sample over the subsequent year. Early high-risk opioid prescribing was associated with double the odds of persistent use (aOR 2.19, 95% CI 1.89-2.53). Injured workers residing in rural areas (inner regional and outer regional/remote Australia) had higher odds of high-risk prescribing (aOR 1.26, 95% CI 1.11-1.44) and (aOR 1.43, 95% CI 1.10-1.87), respectively, compared with those in major cities. Similarly, workers residing in areas with most disadvantaged and advantaged socioeconomic quintile had higher (aOR 1.18, 95% CI 1.01-1.39) and lower (aOR 0.68, 95% CI 0.56-0.82) odds of persistent opioid use, respectively, compared with those in the middle socioeconomic quintiles.</p><p><strong>Conclusions: </strong>A total of two-thirds of injured workers receiving opioids in the first 90 days show evidence of high-risk prescribing, with nearly one-quarter exhibiting persistent opioid use over the subsequent year. Early high-risk opioid prescribing doubles the odds of opioid persistence. There is a need for further research and careful scrutiny of opioid prescribing in this population.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566283","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":"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":"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":"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}

{"title":"Post-marketing Experience with Cenobamate in the Treatment of Focal Epilepsies: A Multicentre Cohort Study.","authors":"Adam Strzelczyk, Felix von Podewils, Hajo M Hamer, Susanne Knake, Felix Rosenow, Kerstin Alexandra Klotz, Gerhard Kurlemann, Nico Melzer, Elisa Buhleier, Catrin Mann, Laurent M Willems, Johann Philipp Zöllner, Bernadette Gaida, Jeanne Cuny, David Bellaire, Ilka Immisch, Leena Kämppi, Andreas Brunklaus, Susanne Schubert-Bast","doi":"10.1007/s40263-025-01158-8","DOIUrl":"10.1007/s40263-025-01158-8","url":null,"abstract":"<p><strong>Background: </strong>In randomised controlled trials, adjunctive cenobamate (CNB) has been shown to reduce seizure frequency in patients with drug-resistant focal epilepsy. Studies conducted in real-world settings provide valuable complementary data to further characterise the drug's profile.</p><p><strong>Objective: </strong>To assess the efficacy, retention and tolerability of adjunctive cenobamate (CNB), and to identify factors that might predict these outcomes in the clinical treatment of focal epilepsies.</p><p><strong>Methods: </strong>This multicentre, retrospective cohort study included all patients who began CNB treatment between October 2020 and April 2023 at seven participating epilepsy centres. Baseline and follow-up data were collected from patients' medical records, covering clinical characteristics and outcome data such as seizure frequency, dosing of CNB, physician-assessed Clinical Global Impression of Change, treatment-emergent adverse events (TEAEs), CNB retention and reasons for discontinuation.</p><p><strong>Results: </strong>A total of 234 patients [mean age 40.7 ± 14 years, median 40 years, range 11-82 years; five adolescents under 18 years; 99 (42.3%) males] were analysed. The mean epilepsy duration at study entry was 23.2 ± 14.5 years (median 21 years, range 0.75-63 years), with the average age of epilepsy onset being 17.5 ± 13.0 years (median 17 years, range 0.1-71 years). The patients were taking a mean of 2.6 ± 0.8 (median 3) anti-seizure medications (ASMs) before starting CNB, and had failed a mean of 6 ± 3.3 (median 6) of further ASMs in the past. CNB exposure ranged from 5 to 1162 days, amounting to a total exposure time of 264.7 years. The retention rate was 92.6% at 3 months, 87.2% at 6 months and 77.8% at 12 months. At 3 months, 52.6% achieved a 50% seizure reduction, with 14.5% reporting seizure freedom; by 12 months, 47.7% maintained a 50% response rate and 11.9% were seizure-free. No significant differences in responder rates were observed based on sex, aetiology, seizure localisation, number of ASMs or target dose. The mean maximum CNB dose was 236.7 ± 97.4 mg (median 200 mg, range 12.5-450 mg), with 28 patients (12.0%) titrated up to 400 mg or above. During CNB treatment, 43.6% of patients were able to discontinue, and a further 24.4% were able to reduce the dose of a concomitant ASM. During CNB treatment, 144 patients (61.5%) experienced TEAEs. The most common TEAEs were sedation (n = 84, 35.9%), dizziness (n = 58, 24.8%) and ataxia (n = 23, 9.8%).</p><p><strong>Conclusions: </strong>CNB showed a relatively high and clinically useful 50% responder rate of 47.7% and an overall retention of 77.8% at 1 year. We were unable to identify specific predictors for response and retention, indicating that CNB may be beneficial for patients with a history of multiple failed ASMs, a high number of concomitant ASMs and any localisation or aetiology of focal epilepsy.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"321-331"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425020","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}