CNS drugs最新文献

{"title":"Effect of Cenobamate on Cognition in Patients with Drug-Resistant Epilepsy with Focal Onset Seizures: An Exploratory Study.","authors":"Pedro J Serrano-Castro, Teresa Ramírez-García, Pablo Cabezudo-Garcia, Guillermina Garcia-Martin, Juan De La Parra","doi":"10.1007/s40263-024-01063-6","DOIUrl":"10.1007/s40263-024-01063-6","url":null,"abstract":"<p><strong>Background and objective: </strong>Most second and third generation antiseizure medications (ASMs) are associated with cognitive adverse events, which are a major concern for patients. However, the profile of cognitive adverse events differs between ASMs. This study investigated the effects of cenobamate on cognition in patients with drug-resistant epilepsy (DRE) within the Spanish Expanded Access Program (EAP).</p><p><strong>Methods: </strong>This was a retrospective, observational study. Inclusion criteria were age ≥ 18 years, DRE with focal seizures, and availability of cognition assessments and EAP authorization. Data were sourced from the clinical records of patients who took part in the Spanish cenobamate EAP. Primary endpoints included cognition (based on 20 neuropsychological outcomes, including verbal and visuospatial episodic memory, verbal fluency, executive function, working memory, attention, and speed of processing), seizure frequency, and concomitant antiseizure medication (ASM) usage at 6 months.</p><p><strong>Results: </strong>The study included 20 patients; 10 patients (50%) had daily seizures, 7 (35%) had weekly seizures and 3 (15%) had monthly seizures. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 10 and 3, respectively. Mean cenobamate doses were 12.5 mg/day at baseline and 191.2 mg/day at 6 months. There was a statistically significant improvement in cognitive scores between baseline and 6 months for two measures of verbal episodic memory (p = 0.0056 and p = 0.0013) and one measure of visuospatial episodic memory (p = 0.011), and a significant worsening in cognitive score for attention (p = 0.030). At 6 months, 14 patients (70%) had a ≥ 50% reduction in seizure frequency, 3 patients (15%) had a ≥ 90% reduction, and 1 patient (5%) was seizure free. There were significant decreases in the mean number of concomitant ASMs (p = 0.0009), the sum of the ratios of prescribing daily dose/daily defined dose (total ratio of DDD) for concomitant ASMs (p < 0.0001), and concomitant ASM drug load (p = 0.038) between baseline and 6 months. Total ratio of DDD was significantly lower at 6 months for perampanel (p = 0.0016), benzodiazepines (p = 0.035), and sodium channel blockers (p = 0.0005) compared with baseline. Based on analysis of covariance, cognitive tests related to verbal or visuospatial episodic memory (e.g., RT of FCSRT, or ROCFT), executive functions (e.g., TMT-B), and processing speed (some 5-Digit Test subtests) appeared to be closely related to the reduction in pharmacological burden rather than the improvement in seizure control.</p><p><strong>Conclusions: </strong>Significant improvements in cognition, seizure frequency, and concomitant ASM usage were observed after the introduction of cenobamate in patients with DRE in a real-world setting. Covariance analysis supports the reduction in concomitant ASMs as the most important factor driving cognitive improvements with cenobama","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"141-151"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541878","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":"Evaluating Monitoring Guidelines of Clozapine-Induced Adverse Effects: a Systematic Review.","authors":"Sarah Smessaert, Johan Detraux, Franciska Desplenter, Marc De Hert","doi":"10.1007/s40263-023-01054-z","DOIUrl":"10.1007/s40263-023-01054-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite the evidence that no other antipsychotic is effective as clozapine for the treatment of resistant schizophrenia, it is associated with various metabolic, neuroendocrine, cardiovascular, and gastrointestinal adverse effects. Guidelines aiming to address the monitoring of clozapine's (serious) adverse effects can be helpful to prevent and treat these effects. However, many of these guidelines seem to lack one or more important monitoring recommendations. We aimed to systematically review the content and quality of existing monitoring guidelines/recommendations for clozapine-induced adverse effects.</p><p><strong>Methods: </strong>A comprehensive and systematic literature search, using the MEDLINE, Embase, Web of Science, and Cochrane databases, was conducted for guidelines/recommendations on the monitoring of clozapine-induced adverse events, published between January 2004 and April 2023 (last search 16 April 2023). Only peer-reviewed published guidelines reporting on the comprehensive monitoring of all major clozapine-induced adverse effects and including evidence-based recommendations, developed after the year 2004, were included. Studies reporting on the monitoring of adverse effects of clozapine without being a formal guideline, guidelines reporting on the monitoring of one or a limited number of adverse effects of clozapine, guidelines that were not peer reviewed or published, expert opinion papers without formal consensus guideline development, or guidelines developed before the year 2004, were excluded. The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool was used to evaluate the guidelines/recommendations' quality.</p><p><strong>Results: </strong>Only one guideline met the inclusion criteria. This consensus statement made recommendations for hematological monitoring, and the monitoring of metabolic, cardiac, and three other adverse effects. Highest scores for the qualitative assessment were found for the domains \"scope and purpose\" (66.7%), \"clarity of presentation\" (44.4%), and \"editorial independence\" (66.7%). Lowest scores were found for \"rigor of development\" (14.6%) and \"applicability\" (0%).</p><p><strong>Conclusions: </strong>Future guidelines should develop more comprehensive recommendations about specific clozapine-induced adverse effects, including constipation, myocarditis, tachycardia, and seizures, as well as include a rechallenge policy. There is an urgent need for well-developed, methodologically stringent, guidelines.</p><p><strong>Registration: </strong>PROSPERO registration number, CRD42023402480.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"105-123"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485278","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 Pannexin-1 Channels: Addressing the 'Gap' in Chronic Pain.","authors":"Brendan B McAllister, Sierra Stokes-Heck, Erika K Harding, Nynke J van den Hoogen, Tuan Trang","doi":"10.1007/s40263-024-01061-8","DOIUrl":"10.1007/s40263-024-01061-8","url":null,"abstract":"<p><p>Chronic pain complicates many diseases and is notoriously difficult to treat. In search of new therapeutic targets, pannexin-1 (Panx1) channels have sparked intense interest as a key mechanism involved in a variety of chronic pain conditions. Panx1 channels are transmembrane proteins that release ions and small molecules, such as adenosine triphosphate (ATP). They are expressed along important nodes of the pain pathway, modulating activity of diverse cell types implicated in the development and progression of chronic pain caused by injury or pathology. This review highlights advances that have unlocked the core structure and machinery controlling Panx1 function with a focus on understanding and treating chronic pain.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"77-91"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729177","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":"Benzodiazepines for the Treatment of Seizure Clusters.","authors":"Patricia E Penovich, Vikram R Rao, Lucretia Long, Enrique Carrazana, Adrian L Rabinowicz","doi":"10.1007/s40263-023-01060-1","DOIUrl":"10.1007/s40263-023-01060-1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Patients with epilepsy may experience seizure clusters, which are described by the US Food and Drug Administration (FDA) as intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. Untreated seizure clusters may increase the risk for status epilepticus, as well as decrease quality of life and increase burden on patients and care partners. Benzodiazepine therapies are the mainstay for acute treatment of seizure clusters and are often administered by nonmedical care partners outside a healthcare facility. Three rescue therapies are currently FDA-approved for this indication, with diazepam rectal gel being the first in 1997, for patients aged ≥  2 years. Limitations of rectal administration (e.g., positioning and disrobing the patient, which may affect ease of use and social acceptability; interpatient variation in bioavailability) led to the investigation of the potential for nasal administration as an alternative. Midazolam nasal spray (MDS) was approved by the FDA in 2019 for patients aged ≥  12 years and diazepam nasal spray (DNS) in 2020 for patients aged ≥  6 years; these two intranasal therapies have differences in their formulations [e.g., organic solvents (MDS) vs. Intravail and vitamin E for absorption and solubility (DNS)], effectiveness (e.g., proportion of seizure clusters requiring only one dose), and safety profiles. In clinical studies, the proportion of seizure clusters for which only one dose of medication was used varied between the three approved rescue therapies with the highest single-dose rate for any time period for DNS; however, although studies for all three preparations enrolled patients with highly intractable epilepsy, inclusion and exclusion criteria varied, so the three cannot be directly compared. Treatments that have been used off-label for seizure clusters in the USA include midazolam for injection as an intranasal spray (indicated for sedation/anxiolysis/amnesia and anesthesia) and tablet forms of clonazepam (indicated for treatment for seizure disorders) and lorazepam (indicated for anxiety). In the European Union, buccal and intranasal midazolam are used for treating the indication of prolonged, acute convulsive seizures and rectal diazepam solution for the indication of epileptic and febrile convulsions; duration of effectiveness for these medications for the treatment of seizure clusters has not been established. This paper examines the literature context for understanding seizure clusters and their treatment and provides effectiveness, safety, and administration details for the three FDA-approved rescue therapies. Additionally, other medications that are used for rescue therapy in the USA and globally are discussed. Finally, the potential benefits of seizure action plans and candidates for their use are addressed. This paper is intended to provide details about the unique characteristics of rescue therapies for seizure clusters to help clar","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"125-140"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10881644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734651","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":"Trends in Pregabalin Use and Prescribing Patterns in the Adult Population: A 10-Year Pharmacoepidemiologic Study","authors":"","doi":"10.1007/s40263-024-01064-5","DOIUrl":"https://doi.org/10.1007/s40263-024-01064-5","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Background and Objective</h3> <p>Pregabalin is steadily gaining popularity worldwide, with epidemiological studies indicating an increase in labeled, off-labeled, and recreational uses. In Israel, pregabalin prescriptions are not regulated by the controlled substances legislations, prompting a need to examine its usage trends for potential policy adjustments. The objective of this study was to assess trends in pregabalin prescribing during a 10-year period, to characterize demographic and clinical characteristics of individuals prescribed pregabalin, and to identify risk factors associated with high-intensity pregabalin use.</p> </span> <span> <h3>Methods</h3> <p>This retrospective, longitudinal study examined trends in pregabalin prescribing from 2010 to 2019 based on data extracted from the Clalit Health Services (CHS) electronic database. Annual pregabalin prescribing rate was calculated individually for each reporting year. A univariable analysis was conducted to compare the demographic and clinical characteristics of pregabalin users in 2019 with those in 2010. Multivariable regression analysis was performed to assess dose-related patterns by specific demographic and clinical characteristics.</p> </span> <span> <h3>Results</h3> <p>Pregabalin prescription rate more than doubled over 10 years [odds ratio (OR) 2.3, <em>p</em> = 0.001], reaching 7.2 [95% confidence interval (CI) 7.18–7.28] prescriptions per 100 CHS members in 2019. The highest prescription rates were observed among the elderly population (13.2 and 24.1 prescriptions per 100 CHS members for those aged 55–74 and over 75 years old, respectively). Same-year administration of pregabalin with opioids, benzodiazepines, and Z-drugs was common; however, the percentage of patients using these drugs together declined in 2019 compared with 2010 (<em>p</em> &lt; 0.001). Males, patients with low socioeconomic status, patients aged 35–54 years, and those who consumed opioids, benzodiazepines, and Z-drugs received higher pregabalin doses.</p> </span> <span> <h3>Conclusion</h3> <p>Pregabalin use has increased significantly in the Israeli adult-based CHS population, consistent with worldwide data. A growing use over time may indicate overprescription. More studies are needed on misuse patterns to identify populations most susceptible to high-dose and high-intensity pregabalin use.</p> </span>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"31 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139560564","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":"Treatment of Sleep, Motor and Sensory Symptoms with the Orexin Antagonist Suvorexant in Adults with Idiopathic Restless Legs Syndrome: A Randomized Double-Blind Crossover Proof-of-Concept Study.","authors":"Diego Garcia-Borreguero, Alba Garcia Aragón, Brian Moncada, Sofia Romero, Juan José Granizo, Sonia Quintas, María Castillo","doi":"10.1007/s40263-023-01055-y","DOIUrl":"10.1007/s40263-023-01055-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Current treatment guidelines for restless legs syndrome (RLS) recommend treatment be initiated with non-dopaminergic drugs. Given the potential role of orexins in the pathophysiology of RLS, we performed a pilot, proof-of-concept study to investigate the therapeutic effects of suvorexant, a dual orexin receptor antagonist (DORA), on sleep and sensory/motor symptoms in individuals with idiopathic RLS.</p><p><strong>Methods: </strong>This was a randomized, double-blind, crossover and placebo-controlled study. Inclusion criteria were diagnosis with idiopathic RLS, an International RLS Study Group Severity Rating Scale (IRLS) score > 15, and the absence of significant RLS symptoms before 9 pm. Following washout from any previous central nervous system (CNS)-active drugs, patients were randomized to receive either suvorexant or placebo for two consecutive 2-week treatment periods. Treatment was administered at 9 pm at a fixed dose of 10 mg/day during the first week, and 20 mg during the second week. Primary and coprimary endpoints were wake after sleep onset (WASO) and total sleep time (TST), respectively, while IRLS rating scale score, multiple suggested immobilization tests (m-SIT), and periodic limb movements (PLMs) were secondary endpoints. RLS severity was measured weekly using the IRLS and Clinical Global Improvement (CGI) scales. m-SIT were also performed between 8 pm and midnight at the end of each treatment phase and were followed by a sleep study.</p><p><strong>Results: </strong>A total of 41 participants were randomized, 40 of whom completed the study. Compared with placebo, treatment with suvorexant significantly improved RLS symptoms (according to IRLS total score, CGI, and the m-SIT), PLM during sleep, and PLM with arousal. Improvement of RLS symptoms was greater in those who had not been exposed to dopaminergic agents in the past. Sleep architecture also improved with significant changes in TST, WASO, sleep onset latency, sleep efficiency, non rapid-eye movement stage 1 (N1) %, non rapid-eye movement stage 2 (N2) %, and rapid eye movement (REM) %. Suvorexant was well tolerated in RLS, with few and mild adverse events.</p><p><strong>Conclusions: </strong>Our results provide the first proof of evidence of the therapeutic efficacy of DORAs in improving sleep and sensory and motor symptoms in RLS. Given orexin's role in pain and sensory processing, potential mechanisms of action are discussed.</p><p><strong>Classification of evidence: </strong>The study provides class II evidence supporting the therapeutic efficacy of suvorexant in patients with RLS with sleep disturbance.</p><p><strong>Trial registration: </strong>EudraCT#: 2017-004580-12.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"45-54"},"PeriodicalIF":6.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511942","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":"Factors Associated with Symptom Stabilization that Allow for Successful Transition from Once-Monthly Paliperidone Palmitate to Three-Monthly Paliperidone Palmitate: A Post Hoc Analysis Examined Clinical Characteristics in Chinese Patients with Schizophrenia.","authors":"Xin Li, Chong Ye, Wanyi Zhang, Miaomiao Jia, Gang Wang","doi":"10.1007/s40263-023-01056-x","DOIUrl":"10.1007/s40263-023-01056-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Identifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score &lt; 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, Z&lt;sub&gt;PANSS&lt;/sub&gt; = -2.21, p = 0.028; Z&lt;sub&gt;CGI-S&lt;/sub&gt; = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"55-65"},"PeriodicalIF":7.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377310","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":"Myasthenia Gravis Treatment: From Old Drugs to Innovative Therapies with a Glimpse into the Future.","authors":"Salvatore Crisafulli, Brigida Boccanegra, Massimo Carollo, Emanuela Bottani, Paola Mantuano, Gianluca Trifirò, Annamaria De Luca","doi":"10.1007/s40263-023-01059-8","DOIUrl":"10.1007/s40263-023-01059-8","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is a rare autoimmune disease that causes debilitating muscle weakness due to impaired neuromuscular transmission. Since most (about 80-90%) MG patients present autoantibodies against the acetylcholine receptor, standard medical therapy consists of symptomatic treatment with acetylcholinesterase inhibitors (e.g., pyridostigmine). In addition, considering the autoimmune basis of MG, standard therapy includes immunomodulating agents, such as corticosteroids, azathioprine, cyclosporine A, and cyclophosphamide. New strategies have been proposed for the treatment of MG and include complement blockade (i.e., eculizumab, ravulizumab, and zilucoplan) and neonatal Fc receptor antagonism (i.e., efgartigimod and rozanolixizumab). The aim of this review is to provide a detailed overview of the pre- and post-marketing evidence on the five pharmacological treatments most recently approved for the treatment of MG, by identifying both preclinical and clinical studies registered in clinicaltrials.gov. A description of the molecules currently under evaluation for the treatment of MG is also provided.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"15-32"},"PeriodicalIF":6.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424463","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":"Thrombolysis with Recombinant Human Prourokinase 4.5-6 h After Acute Ischemic Stroke: A Phase IIa, Randomized, and Open-Label Multicenter Clinical Trial.","authors":"Haiqing Song, Yuan Wang, Qingfeng Ma, Huisheng Chen, Bo Liu, Yi Yang, Jianguo Zhu, Shigang Zhao, Xiaoping Jin, Yongqiu Li, Yanyong Wang, Runxiu Zhu, Liandong Zhao, Junyan Liu, Wuwei Feng, Rui Liu, Xunming Ji, Yuping Wang","doi":"10.1007/s40263-023-01051-2","DOIUrl":"10.1007/s40263-023-01051-2","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a major cause of disability and death worldwide. A narrow therapeutic window profoundly constrained the utilization of alteplase.</p><p><strong>Objectives: </strong>To investigate therapeutic effects and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke (AIS) in the 4.5-6 h therapeutic time windows.</p><p><strong>Methods: </strong>We conducted a phase IIa, randomized, and open-label multicenter clinical trial. Between 4.5 and 6 h after the onset of AIS, patients were randomly administrated to receive intravenous rhPro-UK at a 50 mg or 35 mg dose. The primary endpoint was excellent functional outcome defined as modified Rankin scale (mRS) score of 1 or less at 90 days. The secondary outcome was the treatment response, which was based on an at least 4-point improvement from baseline National Institutes of Health stroke scale (NIHSS) score at 24 h after drug administration. Safety endpoints included death, symptomatic intracerebral hemorrhage (sICH), and other serious adverse events.</p><p><strong>Results: </strong>We enrolled 80 patients in the 4.5-6 h therapeutic time windows at 17 medical centers in China from December 2016 to November 2017. A total of 39 patients were treated with 50 mg rhPro-UK, and 39 were treated with 35 mg rhPro-UK. Compared with the baseline, the NIHSS score at 24 h and days 7, 14, 30, and 90 was decreased significantly among patients treated with either rhPro-UK 50 mg or 35 mg. The mean reduction in the NIHSS from baseline to 90 days after the onset was 3.56 and 5.79 in the rhPro-UK 50 mg group and the rhPro-UK 35 mg group, respectively. The rates of functional independence at 90 days of rhPro-UK 50 mg and 35 mg were 61.54% and 69.23%, respectively (P = 0.475), and the proportion of patients with functional response to treatment at 24 h were 28.21% and 33.33% (P = 0.624). No sICH occurred in the two groups, and death occurred in only one patient in the rhPro-UK 50 mg group. There was no significant difference in mortality at 90 days and the rate of other serious adverse events between two groups.</p><p><strong>Conclusion: </strong>In the 4.5-6 h time window, more than 60% of patients at either dose of rhPro-UK (50 mg or 35 mg) achieved functional independence at 90 days without increased mortality and sICH risk. Thus, intravenous rhPro-UK was effective and safe for patients with AIS within 4.5-6 h after stroke onset. While no significant differences were identified between different dosages of rhPro-UK regarding clinical outcomes, it is a logical step to further test the safety and efficacy of the low dose of rhPro-UK in a well-powered phase III study.</p><p><strong>Trial registration: </strong>http://www.chictr.org.cn . Identifier: ChiCTR1800016519. Date of registration: 6 June 2018.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"67-75"},"PeriodicalIF":7.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10811005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458296","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":"Effect of Levetiracetam on Cognition: A Systematic Review and Meta-analysis of Double-Blind Randomized Placebo-Controlled Trials","authors":"Chia-Yen Lin, Meng-Chia Chang, Hong-Jie Jhou","doi":"10.1007/s40263-023-01058-9","DOIUrl":"https://doi.org/10.1007/s40263-023-01058-9","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was reported in patients with amnestic mild cognitive impairment, schizophrenia, and Alzheimer’s disease. However, the specific cognitive domains affected and the degree of evidence supporting these effects remain unclear. This systematic review and meta-analysis aimed to explore the effects of levetiracetam on different cognitive domains.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We defined our inclusion criteria for the systematic review as: (1) randomized placebo-controlled trials (RCTs) involving human subjects, (2) double-blinded RCTs, and (3) RCTs evaluating the quantitative differences in cognitive function between levetiracetam and placebo. We excluded: (1) non-RCT studies, (2) open-label studies, and (3) RCTs lacking cognitive assessments for either intervention. Two authors independently searched electronic databases, including PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until 2 July 2023. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Meta-analytic techniques were applied to examine the impact of levetiracetam on cognitive domain tests, with Hedges’ &lt;i&gt;g&lt;/i&gt; facilitating the comparison with placebo. The domains analyzed comprised multi-domain, executive function, processing speed, working memory, verbal memory/learning (verbal ML), visuospatial memory/learning (visuospatial ML), and language. We used odds ratios to compare the incidence of treatment-emergent adverse events between the groups, including somnolence, fatigue, dizziness, headache, irritability, and cognitive adverse events.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;A random-effects model was utilized to perform a meta-analysis of 16 RCTs including 545 participants. Compared with a placebo, levetiracetam was associated with improved executive function [Hedges’&lt;i&gt;g&lt;/i&gt; = − 0.390, 95% confidence interval (CI) = − 0.609 to − 0.172, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 24.0%]. Subgroup analysis showed that levetiracetam outperformed placebo in patients without epilepsy (Hedges’ &lt;i&gt;g&lt;/i&gt; = − 0.419, 95% CI = − 0.647 to − 0.191, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 26.2%). Meanwhile, low-dose levetiracetam showed a moderate favorable effect over placebo (Hedges’ &lt;i&gt;g&lt;/i&gt; = −0.544, 95% CI = − 1.085 to − 0.003, &lt;i&gt;p&lt;/i&gt; = 0.049, &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 65.3%). In patients without epilepsy, low-dose levetiracetam was associated with improved executive function (Hedges’&lt;i&gt;g&lt;/i&gt; = − 0.544, 95% CI = − 1.085 to − 0.003, &lt;i&gt;p&lt;/i&gt; = 0.049, &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 65.3%). Concurrently, levetiracetam was associated with mor","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"244 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685975","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}