CNS drugs最新文献

{"title":"Foslevodopa/Foscarbidopa: A Review in Advanced Parkinson's Disease.","authors":"Hannah A Blair","doi":"10.1007/s40263-025-01179-3","DOIUrl":"https://doi.org/10.1007/s40263-025-01179-3","url":null,"abstract":"<p><p>Foslevodopa/foscarbidopa [PRODUODOPA^® (EU); VYALEV^™ (USA, Canada, Japan)] is a soluble formulation of levodopa and carbidopa prodrugs for 24-h continuous subcutaneous (SC) infusion. It is approved for the treatment of motor fluctuations in patients with advanced Parkinson's disease (PD). Administered via an ambulatory infusion pump, it allows for personalized dosing based on individual needs. In a randomized, double-blind, double-dummy trial, continuous SC infusion of foslevodopa/foscarbidopa provided a significant and clinically meaningful increase in hours of 'on' time without troublesome dyskinesia and a reduction in hours of 'off' time compared with oral immediate-release levodopa/carbidopa. The benefits of foslevodopa/foscarbidopa were maintained over the longer term (up to 124 weeks). Continuous SC infusion of foslevodopa/foscarbidopa was generally well tolerated, including over the longer term. However, infusion site events were common, necessitating regular monitoring, cannula replacement, infusion site rotation and aseptic techniques. Although further long-term data are required, foslevodopa/foscarbidopa represents a promising non-surgical alternative to the available device-aided therapies for patients with advanced PD whose motor fluctuations are inadequately controlled by other oral PD medications.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810667","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":"https://doi.org/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":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"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":"Opioid Analgesics: Rise and Fall of Ligand Biased Signaling and Future Perspectives in the Quest for the Holy Grail.","authors":"Émile Breault, Rebecca L Brouillette, Terence E Hébert, Philippe Sarret, Élie Besserer-Offroy","doi":"10.1007/s40263-025-01172-w","DOIUrl":"https://doi.org/10.1007/s40263-025-01172-w","url":null,"abstract":"<p><p>Opioid analgesics have been used for more than 5000 years and remain the main pain medications prescribed today. Although morphine is considered the gold standard of pain relief, this selective µ-opioid receptor (MOP) agonist provides only moderate relief for many chronic pain conditions and produces a number of unwanted effects that can affect the patient's quality of life, prevent adherence to treatment or lead to addiction. In addition to the lack of progress in developing better analgesics, there have been no significant breakthroughs to date in combating the above-mentioned side effects. Fortunately, a better understanding of opioid pharmacology has given renewed hope for the development of better and safer pain medications. In this review, we describe how clinically approved opioids were initially characterized as biased ligands and what impact this approach might have on clinical practice. We also look at the preclinical and clinical development of biased MOP agonists, focusing on the history of oliceridine, the first specifically designed biased analgesic. In addition, we explore the discrepancies between ligands with low intrinsic efficacy and those with biased properties. Finally, we examine the rationale behind the development of biased ligands during the opioid crisis.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762746","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":"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":"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":"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":"Clozapine-Related Tachycardia: An Analysis of Incidence.","authors":"Susanna Every-Palmer, Korinne Northwood, James Tsakas, Matthew K Burrage, Dan Siskind","doi":"10.1007/s40263-025-01177-5","DOIUrl":"https://doi.org/10.1007/s40263-025-01177-5","url":null,"abstract":"<p><strong>Background and objectives: </strong>Sinus tachycardia commonly occurs at the start of clozapine treatment, often leading to discontinuation owing to perceived adverse cardiovascular effects. However, little evidence exists on its natural course after clozapine initiation. We aimed to determine the frequency and course of clozapine-induced tachycardia over the first month of treatment and to identify possible risk factors METHODS: In this cross-sectional study, we serially monitored heart rates (HRs) and other clinical variables of psychiatric inpatients commencing clozapine over the first 28 days. HRs were plotted over time and modelled by explanatory variables, including age group, sex, body mass index (BMI), smoking status and prescribed medications for HR.</p><p><strong>Results: </strong>In total, 123 consecutive inpatients undergoing clozapine titration were assessed daily, with 2901 HR measures collected. After starting clozapine, mean HR increased from 83.7 to 99.5 beats per minute (bpm). Almost all participants (93.5%) had at least one recorded HR > 100 bpm, and 68% had three consecutive days with HR > 100 bpm (being then defined as tachycardic). At least one HR > 120 bpm was recorded in 35.8%, and 8% had persistent HRs > 120 bpm. Tachycardia occurred early during clozapine titration, with a dose response effect at lower doses, which plateaued between 150 and 350 mg daily. Tachycardia spontaneously resolved for some but 44% remained tachycardic at day 28. Female sex was associated with early tachycardia at day 14 (p = 0.008) but not at day 28, while age, smoking status, and BMI were not significantly associated with tachycardia.</p><p><strong>Conclusions: </strong>Sinus tachycardia occurred in over two thirds of participants during the first month of clozapine titration. Spontaneous resolution of tachycardia in some suggests watchful monitoring may be appropriate prior to treatment with rate-controlling agents such as β-blockers or ivabradine. Long term follow-up is required to determine the effects of sinus tachycardia on cardiovascular outcomes in patients treated with clozapine.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691213","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}