CNS drugs最新文献

{"title":"Adjunctive PCSK9 Inhibitor Evolocumab in the Prevention of Early Neurological Deterioration in Non-cardiogenic Acute Ischemic Stroke: A Multicenter, Prospective, Randomized, Open-Label, Clinical Trial.","authors":"Wen Tian, Hua Cao, Xidan Li, Xing Gong, Xinting Yu, Dongyun Li, Jing Xie, Ying Bai, Dawei Zhang, Xiaohong Li, Ping Xu, Jiahui Liu, Bingwei Zhang, Xiaofei Ji, Huijie Dong","doi":"10.1007/s40263-024-01145-5","DOIUrl":"10.1007/s40263-024-01145-5","url":null,"abstract":"<p><strong>Background: </strong>Early neurological deterioration (END) is associated with a poor prognosis in acute ischemic stroke (AIS). Effectively lowering low-density lipoprotein cholesterol (LDL-C) can improve the stability of atherosclerotic plaque and reduce post-stroke inflammation, which may be an effective means to lower the incidence of END. The objective of this study was to determine the preventive effects of evolocumab on END in patients with non-cardiogenic AIS.</p><p><strong>Methods: </strong>This was a multicenter, prospective, open-label, blinded-endpoint clinical trial. Participants with AIS within 24 h were randomly assigned to either the group receiving combination therapy of evolocumab and atorvastatin, which is a 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, i.e., a \"statin\" (PI group), or the group receiving atorvastatin monotherapy (AT group). The primary outcome was END within 7 days, defined as a 2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or a 1-point increase in motor function within 24 h-7 days from the onset of AIS. Secondary outcomes included LDL-C target achievement rate on day 7 (≤ 1.8 mmol/L with a reduction exceeding 50% from baseline), inflammatory factors (interleukin [IL]-6, IL-8, and tumor necrosis factor [TNF]-α) before and after 7 days of treatment, and stroke-related death with 7 days. Safety endpoints included any adverse events.</p><p><strong>Results: </strong>Patients with AIS (n = 272) were randomly assigned to the PI (n = 136) or AT (n = 136) groups. Within 7 days, 18 (13.2%) and 33 (24.3%) patients experienced END in the PI and AT groups, respectively (relative risk [RR] -0.90; 95% confidence interval [CI]: -1.59 to -0.22; p = 0.010). On the seventh day, LDL-C target achievement rate in the PI and AT groups was 74.3% and 14.7%, respectively (RR 3.27; 95% CI: 2.40-4.15; p = 0.001). Changes in IL-6 over 7 days were significantly lower in the PI group compared with the AT group, respectively (median 1.02 [range -1.91, 5.47] versus 2.54 [-0.83, 15.20]; p = 0.033). On the 90th day of follow-up, 83.1% and 65.4% of patients had a modified Rankin Scale score ≤ 2 in the PI and AT groups, respectively (RR 0.51; 95% CI: 0.66-2.66; p = 0.001). There was no significant difference in stroke recurrence between the two groups within 90 days (RR -1.72; 95% CI: -4.57 to 1.13; p = 0.237). Regarding adverse events, 15 and 22 patients in the PI and AT groups, respectively, experienced slight abnormalities in liver and kidney function laboratory values during the 7-day treatment period (odds ratio 0.62; 95% CI: 0.30-1.29; p = 0.203), but no serious adverse events were observed in either group.</p><p><strong>Conclusion: </strong>These results suggest that the combination therapy of evolocumab and atorvastatin within 24 h of AIS onset may effectively reduce the incidence of END compared with atorvastatin monotherapy. Additionally, in the early stages of AIS, th","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"197-208"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926677","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":"Safety and Efficacy of Ecopipam in Patients with Tourette Syndrome: A Systematic Review and Meta-analysis.","authors":"Prateek Kumar Panda, Pragnya Panda, Lesa Dawman, Anand Santosh Mishra, Vinod Kumar, Indar Kumar Sharawat","doi":"10.1007/s40263-024-01140-w","DOIUrl":"10.1007/s40263-024-01140-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ecopipam is a selective antagonist of the dopamine D1 receptor, and its efficacy and safety have recently been explored in several clinical trials involving patients with Tourette syndrome (TS). The objectives of this systematic review were to determine the pooled estimate for efficacy [in terms of reduction in tic Yale Global Tic Severity Scale (YGTSS) scores] and safety of oral ecopipam in subjects with TS.</p><p><strong>Methods: </strong>All clinical trials that explored the efficacy and/or safety of ecopipam in patients with TS were included to determine the pooled estimate for change in YGTSS, Clinical Global Impression (CGI)-TS, and the severity of comorbid attention-deficit hyperactive disorder (ADHD), obsessive compulsion disorder (OCD), and depressive symptoms, as well as the nature and frequency of adverse effects. Case-series, retrospective studies, and case reports were excluded. Databases, such as PUBMED, EMBASE, Cochrane Central Register of Controlled Trials, and SCOPUS were searched to identify these trials using suitable combination of MESH terms/keywords on 15 June 2024. ROB 2.0 and ROBINS-I tool were used to assess the risk of bias in included randomized-controlled trials (RCTs) and non-randomized intervention studies, respectively, and the GRADE system to determine the certainty of the collated evidence.</p><p><strong>Results: </strong>A total of 96 records were identified in the database search and 31 records were screened after removing duplicates. After excluding 23 irrelevant records, the full-text review included 8 records. Finally, six publications from three completed clinical trials (two RCTs, with one having an open-label extension) and one ongoing clinical trial were included. A total of 251 participants were included. The pooled estimate for mean change in YGTSS-TTS from baseline to the completion of the randomization period was statistically better in the ecopipam group compared with the placebo group [mean difference: - 3.0, 95% (confidence interval (CI) - 4.2 to - 1.9, I² = 55%, p < 0.0001]. The ecopipam group also fared statistically better in terms of YGTSS-motor tic score, phonic tic score, as well as CGI-TS-S (p < 0.0001). Changes in depressive and obsessive-compulsive symptoms were comparable in both groups, as well as the incidence of adverse effects.</p><p><strong>Conclusions: </strong>Ecopipam is effective in reducing the severity of tics in subjects with TS and has a good safety profile. However, only a limited number of studies were included in the review, with some having small sample sizes and short duration of follow-up.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"127-142"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892286","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":"Correction: Pharmacokinetic Characteristics of Long‑Acting Injectable Antipsychotics for Schizophrenia: An Overview.","authors":"Christoph U Correll, Edward Kim, Jennifer Kern Sliwa, Wayne Hamm, Srihari Gopal, Maju Mathews, Raja Venkatasubramanian, Stephen R Saklad","doi":"10.1007/s40263-024-01138-4","DOIUrl":"10.1007/s40263-024-01138-4","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"111-112"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715589","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":"Author's Reply to Zhou et al: Comment on \"Effectiveness of Anti-Calcitonin Gene-Related Peptide Medication in Vestibular Migraine: A Retrospective Cohort Study in an Asian Population\".","authors":"Toru Miwa","doi":"10.1007/s40263-024-01135-7","DOIUrl":"10.1007/s40263-024-01135-7","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"109-110"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686112","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 Role of GABA Receptors in Anesthesia and Sedation: An Updated Review.","authors":"Annlin Bejoy Philip, Janette Brohan, Basavana Goudra","doi":"10.1007/s40263-024-01128-6","DOIUrl":"10.1007/s40263-024-01128-6","url":null,"abstract":"<p><p>GABA (γ-aminobutyric acid) receptors are constituents of many inhibitory synapses within the central nervous system. They are formed by 5 subunits out of 19 various subunits: α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3. Two main subtypes of GABA receptors have been identified, namely GABAA and GABAB. The GABAA receptor (GABAAR) is formed by a variety of combinations of five subunits, although both α and β subunits must be included to produce a GABA-gated ion channel. Other subunits are γ, δ, ε, π, and ϴ. GABAAR has many isoforms, that dictate, among other properties, their differing affinities and conductance. Drugs acting on GABAAR form the cornerstone of anesthesia and sedation practice. Some such GABAAR agonists used in anesthesia practice are propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. Ketamine, nitrous oxide, and xenon are not GABAR agonists and instead inhibit glutamate receptors-mainly NMDA receptors. Inspite of its many drawbacks such as pain in injection, quick and uncontrolled conversion from sedation to general anesthesia and dose-related cardiovascular depression, propofol remains the most popular GABAR agonist employed by anesthesia providers. In addition, being formulated in a lipid emulsion, contamination and bacterial growth is possible. Literature is rife with newer propofol formulations, aiming to address many of these drawbacks, and with some degree of success. A nonemulsion propofol formulation has been developed with cyclodextrins, which form inclusion complexes with drugs having lipophilic properties while maintaining aqueous solubility. Inhalational anesthetics are also GABA agonists. The binding sites are primarily located within α⁺/β^- and β⁺/α^- subunit interfaces, with residues in the α⁺/γ^- interface. Isoflurane and sevoflurane might have slightly different binding sites providing unexpected degree of selectivity. Methoxyflurane has made a comeback in Europe for rapid provision of analgesia in the emergency departments. Penthrox (Galen, UK) is the special device designed for its administration. With better understanding of pharmacology of GABAAR agonists, newer sedative agents have been developed, which utilize \"soft pharmacology,\" a term pertaining to agents that are rapidly metabolized into inactive metabolites after producing desired therapeutic effect(s). These newer \"soft\" GABAAR agonists have many properties of ideal sedative agents, as they can offer well-controlled, titratable activity and ultrashort action. Remimazolam, a modified midazolam and methoxycarbonyl-etomidate (MOC-etomidate), an ultrashort-acting etomidate analog are two such examples. Cyclopropyl methoxycarbonyl metomidate is another second-generation soft etomidate analog that has a greater potency and longer half-life than MOC-etomidate. Additionally, it might not cause adrenal axis suppression. Carboetomidate is another soft analog of etom","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"39-54"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496460","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":"The Safety of Alcohol Pharmacotherapies in Pregnancy: A Scoping Review of Human and Animal Research.","authors":"Ebony Quintrell, Danielle J Russell, Sofa Rahmannia, Caitlin S Wyrwoll, Alexander Larcombe, Erin Kelty","doi":"10.1007/s40263-024-01126-8","DOIUrl":"10.1007/s40263-024-01126-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Alcohol pharmacotherapies pose unknown teratogenic risks in pregnancy and are therefore recommended to be avoided. This limits treatment options for pregnant individuals with alcohol use disorders (AUD). The information on the safety of these medications during pregnancy is uncertain, prompting a scoping review. The objective of this review was to investigate available information on the safety of alcohol pharmacotherapies in pregnancy.</p><p><strong>Methods: </strong>Studies published between January 1990 and July 2023 were identified through searches in BIOSIS, Embase, PsycINFO and MEDLINE databases, using terms related to pregnancy and alcohol pharmacotherapies. The alcohol pharmacotherapies investigated were naltrexone, acamprosate, disulfiram, nalmefene, baclofen, gabapentin and topiramate. Studies were screened by two independent reviewers. Covidence software facilitated the management, screening and extraction of studies.</p><p><strong>Results: </strong>A total of 105 studies were included in the review (naltrexone: 21, acamprosate: 4, disulfiram: 3, baclofen: 3, nalmefene: 0, topiramate: 55, gabapentin: 32) with some studies investigating multiple medications. Studies investigating naltrexone's safety in pregnancy focussed on opioid use disorders, with limited evidence regarding its safety in the context of AUD. Despite concerns about higher rates of some pregnancy complications, studies generally indicate naltrexone as a safer option compared with opioid agonists or alcohol during pregnancy. Acamprosate was not clearly associated with adverse effects of exposure in pregnancy, with two pre-clinical studies suggesting potential neuroprotective properties. Disulfiram has a high risk of congenital anomalies when used in pregnancy, believed to be due to its mechanism of action. Prenatal topiramate has also been associated with an increased risk of congenital anomalies, particularly oral clefts. There were mixed results concerning the safety of prenatal gabapentin and little to no literature investigating the safety of baclofen or nalmefene during pregnancy.</p><p><strong>Conclusions: </strong>There is insufficient research on the safety of alcohol pharmacotherapies in pregnancy. Despite this, given alcohol's teratogenic effects, naltrexone could be considered to help maintain abstinence in pregnant individuals with AUD, particularly when psychosocial treatments have failed.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"23-37"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399631","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":"Measuring Disease Progression in Multiple Sclerosis Clinical Drug Trials and Impact on Future Patient Care.","authors":"Floriana De Angelis, Riccardo Nistri, Sarah Wright","doi":"10.1007/s40263-024-01132-w","DOIUrl":"10.1007/s40263-024-01132-w","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterised by inflammation, demyelination and neurodegeneration. Although several drugs are approved for MS, their efficacy in progressive disease is modest. Addressing disease progression as a treatment goal in MS is challenging due to several factors. These include a lack of complete understanding of the pathophysiological mechanisms driving MS and the absence of sensitive markers of disease progression in the short-term of clinical trials. MS usually begins at a young age and lasts for decades, whereas clinical research often spans only 1-3 years. Additionally, there is no unifying definition of disease progression. Several drugs are currently being investigated for progressive MS. In addition to new medications, the rise of new technologies and of adaptive trial designs is enabling larger and more integrated data collection. Remote assessments and decentralised clinical trials are becoming feasible. These will allow more efficient and large studies at a lower cost and with less burden on study participants. As new drugs are developed and research evolves, we anticipate a concurrent change in patient care at various levels in the foreseeable future. We conducted a narrative review to discuss the challenges of accurately measuring disease progression in contemporary MS drug trials, some new research trends and their implications for patient care.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"55-80"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709415","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 Safety of Antipsychotic Medications and Mood Stabilizers During Pregnancy: A Systematic Review and Network Meta-analysis of Congenital Malformations and Prenatal Outcomes.","authors":"Enhui Wang, Yilin Liu, Yucheng Wang, Xinyu Han, Yifang Zhou, Lingli Zhang, Yanqing Tang","doi":"10.1007/s40263-024-01131-x","DOIUrl":"10.1007/s40263-024-01131-x","url":null,"abstract":"<p><strong>Background: </strong>A network meta-analysis was performed to evaluate the risk of congenital malformations and other prenatal outcomes in fetuses after exposure to antipsychotic medications and mood stabilizers during pregnancy.</p><p><strong>Methods: </strong>We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to 15 December 2023, to identify experimental and observational studies comparing antipsychotic and mood stabilizer treatments with control treatments (no exposure). The primary outcome of the study was the incidence of congenital malformations and the secondary outcomes were preterm birth and spontaneous abortion. Additionally, two authors independently assessed the risk of bias in each domain of the included studies using the ROBINS-I tool and evaluated the quality of evidence using the CINeMA rating tool.</p><p><strong>Results: </strong>The literature search identified 18,334 potential records, and 22 studies involving 3,042,997 pregnant women were ultimately included. Compared with the unexposed group, quetiapine [odds ratio (OR), 1.19; 95% credible interval (CrI), 1.01-1.39], aripiprazole (OR, 1.30; 95% CrI 1.10-1.65), olanzapine (OR, 1.33; 95% CrI 1.11-1.64), risperidone (OR, 1.43; 95% CrI 1.18-1.77), and lithium (OR, 1.61; 95% CrI 1.07-2.30) were associated with a slightly increased risk of congenital malformations. In contrast, lamotrigine (OR, 1.21; 95% CrI 0.86-1.64), ziprasidone (OR, 1.14; 95% CrI 0.73-1.72), and haloperidol (OR, 1.26; 95% CrI 0.90-1.75) did not show significant differences compared with the unexposed group, with narrower credible intervals.</p><p><strong>Conclusions: </strong>The evidence from this analysis suggests that, overall, quetiapine has the lowest teratogenic risk when used during pregnancy, making it the safer option for pregnant women. Lamotrigine and haloperidol follow closely behind. At the same time, the use of lurasidone and ziprasidone should be approached with caution, and further clinical studies are necessary to better assess their safety.</p><p><strong>Systematic review registration: </strong>PROSPERO CRD4201811373.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1-22"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615497","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":"Comment on \"Effectiveness of Anti-Calcitonin Gene-Related Peptide Medication in Vestibular Migraine: A Retrospective Cohort Study in an Asian Population\".","authors":"Xin Zhou, Aiping Zhang, Riyang Lin","doi":"10.1007/s40263-024-01134-8","DOIUrl":"10.1007/s40263-024-01134-8","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"107-108"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686118","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":"Effects of One-Year Anti-seizure Treatment with Add-On Cenobamate on Bone Density and Bone Turnover in Adults with Drug-Resistant Focal Epilepsy: An Observational Study.","authors":"Yulia Novitskaya, Andreas Schulze-Bonhage, Elisa Schütz, Martin Hirsch","doi":"10.1007/s40263-024-01137-5","DOIUrl":"10.1007/s40263-024-01137-5","url":null,"abstract":"<p><strong>Background and objective: </strong>Cenobamate is a novel anti-seizure medication (ASM) with unusually high responder rates even in patients with refractory epilepsy. Due to its enzyme-inducing properties, cenobamate could negatively affect bone metabolism, similar to other ASMs; however, effects of long-term cenobamate treatment on bone health have not yet been investigated. The aim of this longitudinal observational study was to assess the effects of 1 year of continuous, adjunctive cenobamate treatment on bone health in patients with drug-resistant, focal epilepsy.</p><p><strong>Methods: </strong>Adult patients from a tertiary epilepsy centre received cenobamate add-on to their concomitant anti-seizure medication. Bone mineral density at femoral neck and lumbar spine, as well as bone formation biomarkers, electrolytes and liver enzymes in serum were assessed at baseline and after 12 months of continuous cenobamate therapy.</p><p><strong>Results: </strong>Forty-seven patients (29 male, median age 40 years) were included in the study. Median daily dose of cenobamate at 12 months was 250 mg. Moderate, yet statistically significant reduction of the T-score at femoral neck but not lumbar spine was found after 1 year of cenobamate treatment, also in a subgroup of patients (n = 37) without enzyme inducers in the comedication. Additionally, we observed statistically significant changes in bone formation biomarkers: decreased serum level of osteocalcin and increased bone-specific alkaline phosphatase. Bone minerals (calcium and phosphorus) as well as vitamin D3 remained unchanged. Parathormone was statistically significantly reduced. There was a highly statistically significant increase in serum gamma-glutamyl transferase (GGT) levels after 12 months of treatment, reflecting an underlying hepatic enzyme induction by cenobamate.</p><p><strong>Conclusion: </strong>A statistically significant decrease of the T-score at femoral neck, as well as prominent alterations in the bone formation biomarkers, suggest an increase in bone turnover after 1 year of cenobamate treatment. The underlying mechanism is most likely attributed to the hepatic enzyme activation, indicated by a prominent elevation of serum GGT. The results alert for bone density control in susceptible patient groups.</p><p><strong>Trial registration number: </strong>DRKS00027568, March 2, 2022 retrospectively registered.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"95-106"},"PeriodicalIF":7.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784339","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}