CNS drugs最新文献

{"title":"Emerging Pharmacological Approaches for Psychosis and Agitation in Alzheimer's Disease.","authors":"Camillo Imbimbo, Matteo Cotta Ramusino, Silvia Leone, Federico Mazzacane, Valentino De Franco, Alberto Gatti, Giulia Perini, Alfredo Costa","doi":"10.1007/s40263-024-01133-9","DOIUrl":"10.1007/s40263-024-01133-9","url":null,"abstract":"<p><p>Psychosis and agitation are among the most distressing neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), linked to faster disease progression and earlier admission to nursing homes. While nonpharmacological treatments may alleviate mild behavioral symptoms, more severe syndromes often require pharmacological intervention. Brexpiprazole is the only medication approved for agitation in AD, although its limited clinical efficacy has raised criticism. No drugs have been approved for treating psychosis in AD, highlighting the critical need for new, effective, and safe treatments. Recent studies have elucidated part of the neurobiological basis of NPSs in the AD brain, offering insights for testing repurposed and novel drugs. We conducted a comprehensive nonsystematic literature review, aiming to provide a critical overview of both current treatments and emerging pharmacological interventions under clinical development for treating psychosis and agitation in AD. Additionally, we present strategies to optimize the clinical development of new drug candidates. We identify three promising compounds that are currently in phase 3 trials: xanomeline-trospium for AD psychosis, and dextromethorphan-bupropion and dexmedetomidine for agitation in AD. We propose that biomarkers linked to the neuropsychiatric traits of AD patients should be identified in dedicated studies and then included in phase 2 dose-range-finding studies with novel compounds to establish biological engagement. Furthermore, phase 3 placebo-controlled studies should be carried out in AD biomarker-confirmed subjects with narrower cognitive impairment ranges and precise NPS severity at screening. Alternative study designs, such as sequential phase approaches, may also be adopted.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"143-160"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766960","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: 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/s40263-024-01147-3","DOIUrl":"https://doi.org/10.1007/s40263-024-01147-3","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074108","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 Complex Relationship Between Cannabis Use and Mental Health: Considering the Influence of Cannabis Use Patterns and Individual Factors.","authors":"Kelly A Sagar, Staci A Gruber","doi":"10.1007/s40263-024-01148-2","DOIUrl":"10.1007/s40263-024-01148-2","url":null,"abstract":"<p><p>The relationship between cannabis use and mental health is complex, as studies often report seemingly contradictory findings regarding whether cannabis use results in more positive or negative treatment outcomes. With an increasing number of individuals using cannabis for both recreational (i.e., non-medical) and medical purposes, it is critical to gain a deeper understanding of the ways in which cannabis may be helpful or harmful for those diagnosed with psychiatric disorders. Although cannabis is composed of hundreds of compounds, studies assessing the effects of \"cannabis\" most often report the impact of delta-9-tetrahydrocannabinol (d9-THC), the primary intoxicating constituent of the plant. While d9-THC has documented therapeutic properties, negative clinical outcomes commonly associated with cannabis are generally related to d9-THC exposure. In contrast, non-intoxicating cannabinoids such as cannabidiol (CBD) show promise as potential treatment options for psychiatric symptoms. In this article, findings from studies and reviews examining the relationship between mental health conditions (mood, anxiety, psychosis, and post-traumatic stress disorder [PTSD]) and cannabis use are summarized to highlight critical variables that are often overlooked, including those associated with cannabis use patterns (e.g., frequency of use, amount used, cannabinoid exposure, product choice, and route of administration). Further, this article explores individual factors (e.g., age, sex, genetics/family history) that likely impact cannabis-related outcomes. Research to date suggests that youth and those with a family history or genetic liability for psychiatric disorders are at higher risk for negative outcomes, while more research is needed to fully understand unique effects related to sex and older age.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"113-125"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926678","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 Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.","authors":"Samuel Frank, Claudia M Testa, Jody Goldstein, Elise Kayson, Blair R Leavitt, David Oakes, Christine O'Neill, Jacquelyn Whaley, Nicholas Gross, Nayla Chaijale, Steve Barash, Mark Forrest Gordon","doi":"10.1007/s40263-024-01139-3","DOIUrl":"10.1007/s40263-024-01139-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This post hoc analysis was conducted to evaluate safety and efficacy among participants who received high-dosage deutetrabenazine treatment (&gt; 48 mg/d) in ARC-HD, an open-label study that assessed long-term safety and efficacy of deutetrabenazine for the treatment of chorea in HD in adults.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;ARC-HD was a single-arm, two-cohort, open-label study. Participants either successfully completed the First-HD study or switched overnight from tetrabenazine to deutetrabenazine. Participants were dosed with deutetrabenazine in a response-driven manner (maximum 72 mg/d allowed). For the current analysis, exposure-adjusted incidence rates (EAIRs) for adverse events of interest were analyzed according to daily dosage (≤ 48 mg/d versus &gt; 48 mg/d), and total maximal chorea (TMC) scores were analyzed by cohort during the stable-dose period.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 116 of the 119 participants enrolled in ARC-HD entered the stable-dose period, where no apparent differences were seen in EAIRs when receiving deutetrabenazine dosages ≤ 48 mg/d (exposure = 177.7 person-years) compared with &gt; 48 mg/d (exposure = 74.1 person-years). Similar results were found among the subset of participants who received deutetrabenazine dosages &gt; 48 mg/d at least once during the study (n = 49, 42%) when their dosage was ≤ 48 mg/d (exposure = 37.9 person-years) versus &gt; 48 mg/d (74.1 person-years). Efficacy analyses were conducted for participants who had TMC scores available (rollover cohort, n = 77; switch cohort, n = 35). For most participants, the lowest deutetrabenazine dosage needed to achieve a TMC response (≥ 30% improvement from baseline) was between 24 and 48 mg/d in both the rollover (n = 57, 74.0%) and switch (n = 16, 46.0%) cohorts. Whereas the dosage needed for a TMC response was independent of baseline TMC score in the rollover cohort, participants with higher baseline TMC scores in the switch cohort required higher dosages to achieve a TMC response during the trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this open-label, long-term study, some participants received deutetrabenazine dosing &gt; 48 mg/d to achieve adequate chorea control. There was no new safety concern or incremental change in the safety profile between dosages of ≤ 48 mg/d and &gt; 48 mg/d. These results include dosages that have not been approved for clinical use, however, they increase our understanding of safety and tolerability of deutetrabenazine doses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinica","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"185-195"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001320","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":"Treatment of Seizures in People with Intellectual Disability.","authors":"Lance Vincent Watkins, Michael Kinney, Rohit Shankar","doi":"10.1007/s40263-024-01149-1","DOIUrl":"10.1007/s40263-024-01149-1","url":null,"abstract":"<p><p>There is a synergistic relationship between epilepsy and intellectual disability (ID), and the approach to managing people with these conditions needs to be holistic. Epilepsy is the main co-morbidity associated with ID, and clinical presentation tends to be complex, associated with higher rates of treatment resistance, multi-morbidity and premature mortality. Despite this relationship, there is limited level 1 evidence to inform treatment choice for this vulnerable population. This review updates the current evidence base for anti-seizure medication (ASM) prescribing for people with ID. Recommendations are made on the basis of evidence and expert clinical opinion and summarised into a Traffic Light System for accessibility. This review builds on work developed through UK's Royal College of Psychiatrists, Faculty of Intellectual Disability Psychiatry and includes newer pragmatic data from the Cornwall UK Ep-ID Research Register, a national research register for England and Wales that has been in existence for the last 10 years. The Register acts as a source for an in-depth exploration of the evidence base for prescribing 'newer' (third generation, specifically post-2004) ASMs. Its findings are discussed and compared. A practical approach to prescribing and choosing ASMs is recommended on the based evidence. This approach considers the drug profile, including adverse effects and clinical characteristics. The review also details newer specialist ASMs restricted to certain epilepsy syndromes, and potential future ASMs that may be available soon. For completeness, we also explore non-pharmacological interventions, including surgeries, to support epilepsy management.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"161-183"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920795","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":"Comment on \"A Multicenter, Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder\"'.","authors":"Chenxi Wang, Huichuan Tian, Jin Shang","doi":"10.1007/s40263-024-01152-6","DOIUrl":"10.1007/s40263-024-01152-6","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"209-210"},"PeriodicalIF":7.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920791","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":"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;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":"Comment on: \"A Prospective Longitudinal Study of the Effects of Eslicarbazepine Acetate Treatment on Bone Density and Metabolism in Patients with Focal‑Onset Epilepsy\".","authors":"Zhongxing Liu, Mengzhe Tian, Lincheng Duan","doi":"10.1007/s40263-025-01157-9","DOIUrl":"https://doi.org/10.1007/s40263-025-01157-9","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064303","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":"Author's Reply to Liu et al.: \"A Prospective Longitudinal Study of the Effects of Eslicarbazepine Acetate Treatment on Bone Density and Metabolism in Patients with Focal‑Onset Epilepsy\".","authors":"Martin Hirsch","doi":"10.1007/s40263-025-01156-w","DOIUrl":"https://doi.org/10.1007/s40263-025-01156-w","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064230","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}