CNS drugs最新文献

{"title":"An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders","authors":"Nora Vanegas-Arroyave, Stanley N. Caroff, Leslie Citrome, Jovita Crasta, Roger S. McIntyre, Jonathan M. Meyer, Amita Patel, J. Michael Smith, Khody Farahmand, Rachel Manahan, Leslie Lundt, Samantha A. Cicero","doi":"10.1007/s40263-024-01078-z","DOIUrl":"https://doi.org/10.1007/s40263-024-01078-z","url":null,"abstract":"<p>Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that “extrapyramidal symptoms” is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"8 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140171498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and Non-pharmacological Approaches for the Management of Neuropathic Pain in Multiple Sclerosis.","authors":"Anastasiia D Shkodina, Mainak Bardhan, Hitesh Chopra, Onyekachi Emmanuel Anyagwa, Viktoriia A Pinchuk, Kateryna V Hryn, Anzhelina M Kryvchun, Dmytro I Boiko, Vinay Suresh, Amogh Verma, Mykhailo Yu Delva","doi":"10.1007/s40263-024-01072-5","DOIUrl":"10.1007/s40263-024-01072-5","url":null,"abstract":"<p><p>Multiple sclerosis is a chronic inflammatory disease that affects the central nervous system and can cause various types of pain including ongoing extremity pain, Lhermitte's phenomenon, trigeminal neuralgia, and mixed pain. Neuropathic pain is a major concern for individuals with multiple sclerosis as it is directly linked to myelin damage in the central nervous system and the management of neuropathic pain in multiple sclerosis is challenging as the options available have limited efficacy and can cause unpleasant side effects. The literature search was conducted across two databases, PubMed, and Google Scholar. Eligible studies included clinical trials, observational studies, meta-analyses, systematic reviews, and narrative reviews. The objective of this article is to provide an overview of literature on pharmacological and non-pharmacological strategies employed in the management of neuropathic pain in multiple sclerosis. Pharmacological options include cannabinoids, muscle relaxants (tizanidine, baclofen, dantrolene), anticonvulsants (benzodiazepines, gabapentin, phenytoin, carbamazepine, lamotrigine), antidepressants (duloxetine, venlafaxine, tricyclic antidepressants), opioids (naltrexone), and botulinum toxin variants, which have evidence from various clinical trials. Non-pharmacological approaches for trigeminal neuralgia may include neurosurgical methods. Non-invasive methods, physical therapy, and psychotherapy (cognitive behavioral therapy, acceptance and commitment therapy and mindfulness-based stress reduction) may be recommended for patients with neuropathic pain in multiple sclerosis. The choice of treatment depends on the severity and type of pain as well as other factors, such as patient preferences and comorbidities. There is a pressing need for healthcare professionals and researchers to prioritize the development of better strategies for managing multiple sclerosis-induced neuropathic pain.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"205-224"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989552","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 Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.","authors":"Michael D Nailor, Kellie J Goodlet, Omar Gonzalez, J Tyler Haller","doi":"10.1007/s40263-024-01065-4","DOIUrl":"10.1007/s40263-024-01065-4","url":null,"abstract":"<p><strong>Background: </strong>Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use.</p><p><strong>Objective: </strong>The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis.</p><p><strong>Methods: </strong>A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose.</p><p><strong>Results: </strong>Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation.</p><p><strong>Conclusions: </strong>Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"225-229"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545020","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 Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.","authors":"Yue Qiao, Jian Gu, Miao Yu, Yuewei Chi, Ying Ma","doi":"10.1007/s40263-024-01067-2","DOIUrl":"10.1007/s40263-024-01067-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Recent clinical trials of anti-Aβ monoclonal antibodies (mAbs) in the treatment of early Alzheimer's disease (AD) have produced encouraging cognitive and clinical results. The purpose of this network meta-analysis (NMA) was to compare and rank mAb drugs according to their efficacy and safety.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials testing various mAbs for the treatment of cognitive decline in patients with AD, up to March 31, 2023. R software (version 4.2.3) along with JAGS and STATA software (version 15.0) were used for statistical analysis. Odds ratio (OR) for binary variables, mean difference (MD) for continuous variables, and their 95% confidence intervals (CI) were utilized to estimate treatment effects and rank probabilities for each mAb in terms of safety and efficacy outcomes. We calculated the surface under the cumulative ranking area (SUCRA) to evaluate each mAb, with higher SUCRA values indicating better efficacy or lower likelihood of adverse events.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Thirty-three randomized controlled trials with a total of 21,087 patients were included in the current NMA, involving eight different mAbs. SUCRA values showed that aducanumab (87.01% and 99.37%, respectively) was the most likely to achieve the best therapeutic effect based on the changes of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores. Donanemab (88.50% and 99.00%, respectively) performed better than other therapies for Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Positron Emission Tomography-Standardized Uptake Value ratio (PET-SUVr). Lecanemab (87.24%) may be the most promising way to slow down the decrease of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score. In the analysis of the incidence of adverse events (subjects with any treatment-emergent adverse event), gantenerumab (89.12%) had the least potential for adverse events, while lecanemab (0.79%) may cause more adverse events. Solanezumab (95.75% and 80.38%, respectively) had the lowest incidence of amyloid-related imaging abnormalities characterized by edema and effusion (ARIA-E) and by cerebral microhemorrhages (ARIA-H) of the included immunotherapies. While SUCRA values provided a comprehensive measure of treatment efficacy, the inherent statistical uncertainty required careful analysis in clinical application.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Despite immunotherapies significantly increasing the risks of adverse events and ARIA, the data suggest that mAbs can effectively improve the cognitive function of patients with mild and moderate AD. According to the NMA, aducanumab was the most likely to achieve significant improvements in different cognitive and clinical assessments (statistically improved MMSE and CDR-SB), followed by donanemab (statistically impr","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"169-192"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012362","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":"Andexanet Alfa: What We Have Learned from Clinical Trials and Real-World Data.","authors":"Senta Frol, Janja Pretnar Oblak, Mišo Šabovič, Pawel Kermer","doi":"10.1007/s40263-024-01071-6","DOIUrl":"10.1007/s40263-024-01071-6","url":null,"abstract":"<p><p>Andexanet alfa is a specific reversal agent for factor Xa inhibitors with immediate reversal of their anticoagulant effect. Andexanet alfa is currently approved for use in patients treated with rivaroxaban and apixaban who have life-threatening or uncontrolled bleeding. New data from both controlled clinical trials and real-world experience are continuously being published, providing greater insight into the clinical characteristics of the drug, such as efficacy and safety. It is worth considering that andexanet alfa could be of benefit in a variety of different clinical scenarios where patients receiving treatment with apixaban and rivaroxaban (and endoxaban) have life-threatening conditions. These different clinical scenarios, which range from pre-treatment of urgent surgery, especially neurosurgical interventions, and concomitant use of andexanet alfa and prothrombin complex concentrate to onset of bleeding more than 6 h prior to admission, should be clarified as well as the issue of \"low/high\" dose of andexanet alfa and the need for baseline anti-Xa inhibitor levels measured by point-of-care testing. Finally, management of patients at high risk of thrombosis or recent arterial/venous thrombotic events needs to be further explored. In this current opinion, we address these urgent questions in the light of recent literature and clinical trial data.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"163-168"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939775","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":"Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.","authors":"Lucienne Costa-Frossard França, Virginia Meca Lallana, Andrés Labiano-Fontcuberta, Rosario Blasco, Enric Monreal, María Luisa Martínez Ginés, Clara Aguirre, Julia Sabin Muñoz, Susana Sainz de la Maza, Juan Pablo Cuello, Carolina Díaz-Pérez, Juan Luis Chico García, Alberto Lozano Ros, Fernando Rodríguez Jorge, Susana Martínez Martínez, José Manuel García Domínguez","doi":"10.1007/s40263-024-01066-3","DOIUrl":"10.1007/s40263-024-01066-3","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use.</p><p><strong>Objective: </strong>The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug.</p><p><strong>Methods: </strong>A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart.</p><p><strong>Results: </strong>ARR decreased from 1.9 (95% confidence interval 1.60-2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17-0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13-0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18-0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported.</p><p><strong>Conclusions: </strong>This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"231-238"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10920415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989553","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":"Unmet Needs in Psychodermatology: A Narrative Review.","authors":"Rachel E Christensen, Mohammad Jafferany","doi":"10.1007/s40263-024-01068-1","DOIUrl":"10.1007/s40263-024-01068-1","url":null,"abstract":"<p><p>Psychodermatology, the multidisciplinary field that explores the intricate interplay between the mind and the skin, has gained increasing recognition over the past decade. However, several knowledge gaps and unmet needs persist in the field. The objective of this narrative review was to investigate the unmet needs in the field of psychodermatology as they pertain to medical training, treatment, research, and care access. PubMed was searched from inception through December 2023 to identify articles related to psychodermatology. Findings revealed several unmet needs within the field of psychodermatology. First, there is a need for further investigation into the pathophysiology that links psychological stress to cutaneous disease including the development of novel therapies targeting key neuropeptides. Second, the existing literature focuses primarily on the pharmacologic treatment of body dysmorphic disorder and body-focused repetitive behaviors, as well as delusional parasitosis, for which the first-line agents are selective serotonin reuptake inhibitors and atypical antipsychotics, respectively. However, additional research into the efficacy and safety of the remaining psychotropic medications and the treatment of other common psychocutaneous diseases is required. Finally, there exists a significant gap in knowledge amongst clinicians tasked with treating psychocutaneous diseases. Dermatologists report low rates of training in psychodermatology and discomfort with prescribing psychotropic medications. In conclusion, increasing resources for dermatologist education on psychotropic agent use, development of new drugs targeting stress-induced skin conditions, and research on the psychocutaneous applications of current medications may greatly improve the quality and access of psychodermatology care.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"193-204"},"PeriodicalIF":6.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930372","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 Efficacy and Safety of Different Targeted Drugs for the Treatment of Generalized Myasthenia Gravis: A Systematic Review and Bayesian Network Meta-analysis.","authors":"Yongbo Ma, Xiangtao Nie, Geke Zhu, Wenjing Qi, Lei Hao, Xiuming Guo","doi":"10.1007/s40263-024-01062-7","DOIUrl":"10.1007/s40263-024-01062-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The treatment of generalized myasthenia gravis (gMG) has been transformed by the development and approval of new targeted therapies. This analysis aimed to rank and compare the new therapies for gMG using efficacy and safety data from randomized controlled trials (RCTs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (up to November 2022) for RCTs of targeted drugs for gMG. We used a Bayesian random-effects network meta-analysis (NMA) model and a Markov chain Monte Carlo (MCMC) model for statistical analysis. The primary outcome was the change in quantitative myasthenia gravis score (QMGS) from baseline, while the secondary outcome was the risk ratio (RR) of adverse events (AEs) during treatment. The surface under the cumulative ranking curve (SUCRA) was used to rank these targeted drugs, with higher SUCRA values indicating better efficacy or lower likelihood of AEs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 13 studies (872 subjects) were included in this analysis evaluating 10 targeted drugs (batoclimab, belimumab, CFZ533, eculizumab, efgartigimod, nipocalimab, rituximab, ravulizumab, rozanolixizumab, and zilucoplan). With regards to the primary outcome, batoclimab [standardized mean difference (SMD), - 1.61; 95% credible interval (CrI), - 2.78, - 0.43] significantly reduced QMGS in patients with gMG when compared with placebo and was ranked as the most efficacious drug. Ranked second and third were eculizumab (SMD, - 0.67; 95% CrI, 1.43, 0.01) and zilucoplan (SMD, - 0.54; 95% CrI, - 1.56, 0.46), respectively. Nipoclimab (SMD, - 0.02; 95% CrI, - 1.04, 1.00) had the worst efficacy and ranked last among all targeted drugs. In our study, except for batoclimab, there was no statistically significant difference in the reduction of patient QMGS for the remaining targeted agents compared with placebo. With regards to the secondary outcomes, only batoclimab (RR, 0.19; 95% CrI, 0, 0.97) led to a significant reduction in the incidence of AEs when compared with the placebo. Belimumab (RR, 0.85; 95% CrI, 0.57, 1.19), CFZ533 (RR, 0.95; 95% CrI, 0.72, 1.25), eculizumab (RR, 0.99; 95% CrI, 0.85, 1.21), and efgartigimod (RR, 0.93; 95% CrI, 0.76, 1.15) also led to a lower incidence of AEs, although these effects were not significantly different from the placebo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Batoclimab had the best efficacy and safety for the treatment of gMG and was ranked first out of the 10 targeted drugs included in this study. Eculizumab was ranked second, and nipocalimab had the worst efficacy. With the exception of batoclimab, the incidence of AEs for the remaining drugs was not statistically significantly different from placebo. We note, however, that wide CrIs reflect the uncertainty in this analysis owing to the small number of available studies and low numbers of study participants; moreover, batoclimab had the widest","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"93-104"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of 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":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;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).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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 &lt; 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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;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}