CNS drugs最新文献

{"title":"Relationship between Tranexamic Acid Use and Safety in Patients with Acute Brain Injury: A Systematic Review and Meta-analysis of Mortality and Thromboembolic Events.","authors":"Seungjoo Lee, Moinay Kim, Sae Min Kwon, Min-Yong Kwon, Chang-Hyun Kim, Nak-Hoon Son, Jae Hyun Kim","doi":"10.1007/s40263-025-01185-5","DOIUrl":"https://doi.org/10.1007/s40263-025-01185-5","url":null,"abstract":"<p><strong>Background: </strong>Tranexamic acid (TXA) is widely used to manage acute brain injuries, including subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. Despite its common usage, there is limited evidence on its safety in these conditions. We aimed to evaluate the impact of TXA on mortality and thromboembolic events in patients with acute brain injury.</p><p><strong>Methods: </strong>A systematic search of MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted from inception to May 2024. We included randomized controlled trials (RCTs) comparing TXA with placebo in patients aged 15 years or older with confirmed acute brain injury. Two reviewers independently assessed study quality using the revised Cochrane Risk of Bias tool and extracted data on patient demographics, intervention details, and outcomes, including mortality, thromboembolic events, and seizures. Meta-analyses were performed using random effects models.</p><p><strong>Results: </strong>Twenty-five RCTs with 16,677 participants (8584 TXA, 8093 control) were included. The relative risk (RR) for overall mortality was 0.96 (95% confidence interval (CI) 0.91-1.03, p = 0.2433), indicating a nonsignificant difference between the groups, with no substantial heterogeneity (I² = 0% [0-45%]). Additionally, no significant differences were observed in 30-, 90-, or 180-day mortality. The RR for total thromboembolic events was 1.11 (95% CI 0.97-1.28, p = 0.1236), indicating a nonsignificant difference between the groups, with low heterogeneity (I² = 15% [0-51%]). Similarly, no significant differences were observed in the incidences of deep vein thrombosis or pulmonary embolism, ischemic stroke or transient ischemic attack, acute coronary syndrome or myocardial infarction, or seizures. However, the administration of TXA for more than 1 day was associated with a significant increase in thromboembolic events (RR 1.22, 95% CI 1.03-1.44). Administering TXA beyond 8 h of injury was also associated with a significant increase in thromboembolic events (RR 1.16, 95% CI 1.02-1.33).</p><p><strong>Conclusions: </strong>TXA administration does not significantly affect overall mortality or increase the risk of thromboembolic events in patients with acute brain injuries. However, prolonged use or delayed administration may be associated with an increased risk of thromboembolic events. These findings highlight the need for careful consideration of the duration and timing of TXA administration in clinical practice.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957334","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":"Cenobamate: A Review in Focal-Onset Seizures.","authors":"Tina Nie, Sheridan M Hoy","doi":"10.1007/s40263-025-01178-4","DOIUrl":"https://doi.org/10.1007/s40263-025-01178-4","url":null,"abstract":"<p><p>Cenobamate (Ontozry^®) is a once-daily oral antiseizure medication (ASM) approved in the EU for the adjunctive treatment of focal-onset seizures, with or without secondary generalisation, in adults with epilepsy that have not been adequately controlled despite previous treatment with ≥ 2 anti-epileptic drugs. In clinical studies, its short-term use significantly reduced seizure frequency and was associated with significantly higher odds of achieving a ≥ 50% reduction in seizure frequency in adults with uncontrolled focal-onset seizures despite treatment with 1-3 concomitant ASMs. Seizure freedom rates were also improved. All these benefits were sustained over up to 48 months. Cenobamate was generally well tolerated across both the short- and longer-term (up to 94 months) clinical studies, with its low starting dosage (12.5 mg/day) and slow (12-week) titration schedule appearing to result in fewer severe treatment-emergent adverse events (TEAEs) during the titration period. Somnolence, dizziness and fatigue were the most frequently reported TEAEs. The effectiveness and adverse events of cenobamate in real-world studies were consistent with those seen in the clinical studies. Thus, cenobamate continues to represent a useful adjunctive treatment option in adults with uncontrolled focal-onset seizures.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971752","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 Naltrexone on Spinal and Supraspinal Pain Mechanisms and Functional Capacity in Women with Fibromyalgia: Exploratory Outcomes from the Randomized Placebo-Controlled FINAL Trial.","authors":"Karin Due Bruun, Robin Christensen, Kirstine Amris, Morten Rune Blichfeldt-Eckhardt, Lars Bye-Møller, Marius Henriksen, Tine Alkjaer, Palle Toft, Anders Holsgaard-Larsen, Henrik Bjarke Vaegter","doi":"10.1007/s40263-025-01183-7","DOIUrl":"https://doi.org/10.1007/s40263-025-01183-7","url":null,"abstract":"<p><strong>Background: </strong>The widespread pain and muscular fatigue characteristics of fibromyalgia are believed to be mediated by central mechanisms. Low-dose naltrexone (LDN) has emerged as a new treatment option for fibromyalgia, possibly modulating central mechanisms via glial or opioid receptors.</p><p><strong>Methods: </strong>In the randomized, placebo-controlled FINAL trial, 99 women with fibromyalgia were treated with LDN or placebo for 12 weeks. In this secondary analysis, we examined the potential effects of LDN versus placebo on changes from baseline in pain tolerance, temporal summation of pain, and conditioned pain modulation (CPM) in the complete case population (45 versus 47 participants). Measures of muscular fatigue were evaluated using the 30-s chair stand test and a shoulder abduction test.</p><p><strong>Results: </strong>Of the five examined outcomes, only change in CPM showed a significant between-group difference with greater enhancement following LDN treatment (2.0 kPa; 95% confidence interval (CI) 0.4-3.7 kPa) compared with placebo. Within-group changes in CPM showed an increase of 1.2 kPa (95% CI 0.05-2.4 kPa) in the LDN group and a possible decrease of 0.8 kPa (95% CI - 1.9 to 0.4 kPa) in the placebo group.</p><p><strong>Conclusions: </strong>We found a significant between-group difference in CPM change in favor of LDN. However, this difference was partly explained by a decrease in CPM in the placebo group. Sensitivity analyses showed no association between changes in CPM and clinical pain improvement, suggesting that the group-difference in CPM is a random finding.</p><p><strong>Study registration: </strong>ClinicalTrials.gov (NCT0427877; registered on 30 January 2020).</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969098","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}