CNS drugs最新文献

{"title":"Motor and Non-motor Complications Following Different Early Therapies in Parkinson's Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort.","authors":"Aymeric Lanore, Edouard Januel, Nathalie Bertille, Margherita Fabbri, Louise-Laure Mariani, Graziella Mangone, Sara Sambin, Poornima Jayadev Menon, Melissa Tir, Matthieu Bereau, Wassilios G Meissner, Claire Thiriez, Ana Marques, Philippe Remy, Gwendoline Dupont, Elena Moro, Luc Defebvre, Jean Luc Houeto, Stéphane Thobois, Jean-Philippe Azulay, Christian Geny, Solène Frismand, Philippe Damier, Caroline Giordana, Giovanni Castelnovo, Solène Ansquer, Anne Doe De Maindreville, Sophie Drapier, David Maltête, Christine Tranchant, Olivier Rascol, Florence Tubach, Yann De Rycke, Jean-Christophe Corvol","doi":"10.1007/s40263-025-01193-5","DOIUrl":"https://doi.org/10.1007/s40263-025-01193-5","url":null,"abstract":"<p><strong>Background: </strong>Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.</p><p><strong>Methods: </strong>NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.</p><p><strong>Results: </strong>We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.</p><p><strong>Conclusions: </strong>In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT04888364. Registered June 2021.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Safety Profile of Pridopidine, a Novel Sigma-1 Receptor Agonist for the Treatment of Huntington's Disease.","authors":"Yigal Paul Goldberg, Leehee Navon-Perry, Andrés Cruz-Herranz, Kelly Chen, Gabriele Hecker-Barth, Katrin Spiegel, Yael Cohen, Martin Niethammer, Andrew M Tan, Henk Schuring, Michal Geva, Michael R Hayden","doi":"10.1007/s40263-025-01171-x","DOIUrl":"10.1007/s40263-025-01171-x","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is a rare, fatal, chronic progressive neurodegenerative disorder with a significant unmet medical need for effective treatments. Pridopidine is a novel, first-in-class, highly selective and potent sigma-1 receptor (S1R) agonist in development for HD. Pridopidine has been extensively studied in adult HD across the full spectrum of disease severity and age ranges, and its safety profile has been characterized in approximately 1600 participants across multiple studies and a broad range of doses. The specific objective of this study was to gain an in-depth understanding of pridopidine's safety profile at the recommended human dose of 45 mg twice daily (bid) in patients with HD.</p><p><strong>Methods: </strong>An integrated safety analysis of pooled data from 1067 patients with HD enrolled in four double-blind, placebo-controlled studies was performed. The safety profile of pridopidine was compared with placebo.</p><p><strong>Results: </strong>Pridopidine was found to be generally safe and well tolerated with an adverse event (AE) profile comparable to that of placebo. Moreover, there were no significant differences observed in the safety profile of pridopidine compared with placebo when analyzed by age, sex, baseline total functional capacity (TFC), cytosine-adenine-guanine (CAG) repeat length, use of antidopaminergic medications (ADMs), and region.</p><p><strong>Conclusions: </strong>The integrated analysis replicated and corroborated the good safety profile observed in the individual studies. Despite the larger sample size, no new safety signals emerged. Long-term exposure to pridopidine, up to 6.5 years in open-label extension studies, revealed no new safety concerns, supporting its potential for long-term use in patients with HD.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"485-498"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is the Effect of Intensive Antihypertensive Treatment in Acute Intracerebral Hemorrhage Dependent on Hematoma Volume? A Traditional Meta-analysis of the Effect of Antihypertensive Regimens, a Bayesian Network Meta-analysis of the Mortality of Antihypertensive Drugs and Systematic Review.","authors":"Cong Li, Lishuai Li, Zhi Li, Kunhang Li, Xin Shi, Yijun Bao","doi":"10.1007/s40263-025-01174-8","DOIUrl":"10.1007/s40263-025-01174-8","url":null,"abstract":"<p><p>BACKGROUND AND OBJECTIVES: Intensive or conventional antihypertensive treatment for acute intracerebral hemorrhage is still controversial. This study aimed to compare those antihypertensive regimens and analyze the efficacy of antihypertensive drugs.</p><p><strong>Methods: </strong>Retrieval was conducted through four databases. Meta-analysis and Bayesian network meta-analysis were performed to evaluate the safety of antihypertensive treatments and the efficacy of antihypertensive drugs.</p><p><strong>Results: </strong>A total of 9271 patients were included. Intensive strategy showed an advantage in 24-h hematoma enlargement (relative risk, RR = 0.76; 95% confidence intervals, CI = 0.67-0.87; P < 0.0001) and 90-day intracranial rebleeding (RR = 0.71, 95% CI = 0.52-0.96, P = 0.03) compared with conventional strategy. Meanwhile, the 90-day renal insufficiency (RR = 2.31, 95% CI = 1.05-5.05, P = 0.04) and renal failure (RR = 2.42, 95% CI = 1.20-4.86, P = 0.01) were increased. When cerebral hematoma volume was less than 15 ml, intensive strategy had a protective effect on 24-h hematoma enlargement (RR = 0.77, 95% CI = 0.67-0.89, P = 0.0003), but it increased 90-day renal failure (RR = 2.33, 95% CI = 1.07-5.04, P = 0.03). For the volume greater than 15 ml, it enhanced 90-day functional independence (RR = 0.78, 95% CI = 0.65-0.94, P = 0.01) and decreased intracranial rebleeding (RR = 0.68, 95% CI = 0.49-0.94, P = 0.02). Labetalol was the best, with the mortality risk probability of 0.09 and the surface under the cumulative ranking curve of 0.33.</p><p><strong>Conclusions: </strong>This meta-analysis suggests that for intracerebral hematoma volume greater than 15 ml, intensive antihypertensive treatment can improve functional independence and reduce intracranial bleeding. Labetalol has the best effect among the four antihypertensive regimens studied.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"443-456"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Effectiveness of Adjunctive Cenobamate in Focal Epilepsy: A Time-Based Analysis.","authors":"Roberta Roberti, Gianfranco Di Gennaro, Vittoria Cianci, Alfredo D'Aniello, Carlo Di Bonaventura, Giancarlo Di Gennaro, Francesco Fortunato, Edoardo Fronzoni, Alessandra Morano, Angelo Pascarella, Eleonora Rosati, Ilaria Sammarra, Emilio Russo, Simona Lattanzi","doi":"10.1007/s40263-025-01166-8","DOIUrl":"10.1007/s40263-025-01166-8","url":null,"abstract":"<p><strong>Background: </strong>A growing body of evidence supports the effectiveness of cenobamate (CNB). This study aimed to assess the clinical response to add-on CNB through a time-to-event approach and explore the potential contribution of the concomitant classes of antiseizure medications (ASMs) to improve CNB clinical use.</p><p><strong>Patients and methods: </strong>This study is a subgroup analysis of a larger retrospective, multicenter study on adults with focal-onset seizures participating in the Italian Expanded Access Program at five pre-established centers. The primary endpoint was the time-to-baseline seizure count; secondary endpoints included the rates of seizure response, seizure freedom (defined as no seizures' occurrence since at least the previous follow-up visit), treatment discontinuation, and adverse events (AEs).</p><p><strong>Results: </strong>Data on 92 participants were extracted, with a median age of 44 (first quartile (Q₁)-third quartile (Q₃): 29.25-50.75) years. The number of seizures recorded during the 90-day baseline was reached by 59/92 (64.1%) subjects during the 12-month follow-up. A higher, but not statistically significant probability of reaching the baseline seizures count was shown in the subgroups of subjects taking CNB with sodium channel blockers (SCBs) (hazard ratio [HR] 2.75; 95% confidence interval [CI] 0.79-9.61, p = 0.112) and both SCBs and GABAergics (HR 1.48; 95% CI 0.43-5.09, p = 0.536) compared with subjects taking GABAergics without SCBs. At 12 months, the rates of seizure response, seizure-freedom, and treatment discontinuation were 42.0%, 13.6%, and 23.9%, respectively. A total of 47/92 (51.1%) subjects experienced AEs (mainly somnolence, dizziness, and balance disorders) at a median time of 61 (Q₁-Q₃: 30-101) days. There was a higher, but not statistically significant risk of AEs occurrence in subjects treated with both SCBs and GABAergics and in those taking SCBs without GABAergics (HR 2.24; 95% CI 0.51-9.82, p = 0.286 and HR 1.40; 95% CI 0.31-6.39, p = 0.661, respectively) compared with those taking GABAergics without SCBs. The main limitations are the retrospective design and the small sample size.</p><p><strong>Conclusions: </strong>This time-to-event analysis added new insights to the currently available evidence about the real-world effectiveness of add-on CNB. Explorative estimates suggested favorable trends for subjects treated with concomitant GABAergics and without SCBs, who seemed to reach baseline seizure count and experience AEs less frequently and later than subjects treated with other concomitant ASMs. Further studies are needed to identify the best combinations of CNB with other ASMs to maximize seizure control and tolerability.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"513-523"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522553","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":"ADHD and Alcohol Use Disorder: Optimizing Screening and Treatment in Co-occurring Conditions.","authors":"Mariely Hernández, Frances R Levin, Aimee N C Campbell","doi":"10.1007/s40263-025-01168-6","DOIUrl":"10.1007/s40263-025-01168-6","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is notably overrepresented in substance use treatment centers, with an estimated prevalence of 21-23% when screening practices are implemented. Many adults in these settings receive an ADHD diagnosis for the first time, highlighting the frequent underdiagnosis of ADHD among individuals seeking treatment for alcohol and substance use issues. Additionally, those entering treatment programs represent only a small fraction of the broader population with problematic alcohol use. This review explores the research on the prevalence and treatment of co-occurring ADHD and substance use disorders (SUD), with a particular emphasis on alcohol use disorders (AUD) as the most common SUD. It also provides clinical guidelines for the screening and diagnosis of ADHD in patients with active alcohol and substance use and offers recommendations to enhance screening practices and improve access to treatment for individuals with co-occurring ADHD and AUD.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"457-472"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on Neuroprotection after Traumatic Brain Injury.","authors":"Aaron M Cook, Morgan Michas, Blake Robbins","doi":"10.1007/s40263-025-01173-9","DOIUrl":"10.1007/s40263-025-01173-9","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a prevalent cause of morbidity and mortality worldwide. A focus on neuroprotective agents to prevent the secondary injury cascade that follows moderate-to-severe TBI has informed the field greatly but has not yielded any viable therapeutic options to date. New strategies and pharmacotherapy options for neuroprotection continue to be evaluated, including tranexamic acid, progesterone, cerebrolysin, cyclosporin A, citicholine, memantine, and lactate. Biomarkers of injury that can aid in diagnosis and prognosis have also been elucidated and are incrementally being used in clinical practice. The spectrum of TBI severity has also gained increasing attention as it relates to mild TBI or concussion, blast injury, and subacute or chronic subdural hematomas. In this review, we review the pathophysiology, recent clinical trials, and future directions for acute TBI.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"473-484"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early High-Risk Opioid Prescribing and Persistent Opioid Use in Australian Workers with Workers' Compensation Claims for Back and Neck Musculoskeletal Disorders or Injuries: A Retrospective Cohort Study.","authors":"Yonas Getaye Tefera, Shannon Gray, Suzanne Nielsen, Michael Di Donato, Alex Collie","doi":"10.1007/s40263-025-01169-5","DOIUrl":"10.1007/s40263-025-01169-5","url":null,"abstract":"<p><strong>Background: </strong>Opioid prescribing to injured workers has increased despite evidence demonstrating that risks often outweigh the benefits. High-risk prescribing and persistent opioid use are often associated with harm. However, there are limited data on what predicts early high-risk and persistent opioid prescribing in Australian workers with back and neck-related injuries or disorders.</p><p><strong>Objective: </strong>The purpose of this study was to determine the prevalence and identify determinants of early high-risk and persistent opioid prescribing in Australian workers with back and neck conditions.</p><p><strong>Methods: </strong>A retrospective cohort study was carried out with injured workers with workers' compensation claims for back and neck conditions who filled at least one opioid prescription within the first 90 days after injury from 1 January 2010 to 31 December 2019. High-risk opioid prescribing practices in the first 90 days were measured using one of four indicators of risk (high-total opioid volume on first dispensing occasion-exceeding 350 mg oral morphine equivalent in the first week, average high-dose over 90 days-higher than 50 mg oral morphine equivalent, early supply with long-acting opioids, and concurrent psychotropic prescriptions). Persistent opioid use was determined using group-based trajectory modeling over the subsequent 1-year. Multivariable logistic regression was used to identify predictors of high-risk opioid prescribing in the first 90 days and persistent opioid use in the subsequent year.</p><p><strong>Results: </strong>A total of 6278 injured workers prescribed opioids were included. At least one indicator of high-risk opioid prescribing was identified in 67.1% of the sample in the first 3 months. Persistent opioid use was identified in 22.8% of the sample over the subsequent year. Early high-risk opioid prescribing was associated with double the odds of persistent use (aOR 2.19, 95% CI 1.89-2.53). Injured workers residing in rural areas (inner regional and outer regional/remote Australia) had higher odds of high-risk prescribing (aOR 1.26, 95% CI 1.11-1.44) and (aOR 1.43, 95% CI 1.10-1.87), respectively, compared with those in major cities. Similarly, workers residing in areas with most disadvantaged and advantaged socioeconomic quintile had higher (aOR 1.18, 95% CI 1.01-1.39) and lower (aOR 0.68, 95% CI 0.56-0.82) odds of persistent opioid use, respectively, compared with those in the middle socioeconomic quintiles.</p><p><strong>Conclusions: </strong>A total of two-thirds of injured workers receiving opioids in the first 90 days show evidence of high-risk prescribing, with nearly one-quarter exhibiting persistent opioid use over the subsequent year. Early high-risk opioid prescribing doubles the odds of opioid persistence. There is a need for further research and careful scrutiny of opioid prescribing in this population.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"499-512"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Antiseizure Medications and Sudden Unexpected Death in Epilepsy: An Updated Review.","authors":"Anemoon T Bosch, Josemir W Sander, Roland D Thijs","doi":"10.1007/s40263-025-01176-6","DOIUrl":"10.1007/s40263-025-01176-6","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"525"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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":"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}