CNS drugs最新文献

{"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":"10.1007/s40263-025-01156-w","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"335-336"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850453/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narcolepsy: Beyond the Classic Pentad.","authors":"Anne Marie Morse, Seung Yun Kim, Shelby Harris, Monica Gow","doi":"10.1007/s40263-024-01141-9","DOIUrl":"10.1007/s40263-024-01141-9","url":null,"abstract":"<p><p>Narcolepsy is a rare, disabling, chronic neurologic disorder that requires lifelong management of symptoms with pharmacologic and nonpharmacologic methods. The pentad symptoms of narcolepsy include excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, sleep paralysis, and hypnagogic/hypnopompic hallucinations. However, people with narcolepsy often experience additional symptoms and disability related to nonpentad symptoms and comorbidities, such as cognitive, psychiatric, metabolic, and sleep disturbances. Current treatment strategies have focused primarily on addressing two of the pentad symptoms, excessive daytime sleepiness, and cataplexy, mainly owing to medication options being approved by the US Food and Drug Administration for these specific indications, neglecting the full 24-h impact and spectrum of symptoms. Meanwhile, the burden of disease extends far beyond these symptoms, and optimal management should reflect a comprehensive, patient-specific approach that not only addresses the entire pentad, but also goes beyond it to include the complete clinical presentation and manifestations of the disease. Individualized treatment must consider the patient's age and stage of life, most debilitating symptoms, support system and structure, comorbid conditions, treatment goals, and overall health. This review discusses care considerations for people living with narcolepsy in the context of their clinical characteristics beyond the hallmark features of narcolepsy.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"9-22"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668765","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":"Sodium Oxybate: Practical Considerations and Patient Perspectives.","authors":"Maggie Lavender, Cecile Martin, Diana Anderson","doi":"10.1007/s40263-024-01144-6","DOIUrl":"10.1007/s40263-024-01144-6","url":null,"abstract":"<p><p>Narcolepsy is a rare, chronic sleep disorder with significant impacts on the quality of life of people affected by the disorder. People with narcolepsy (PWN) are a diverse patient population with evolving symptoms, comorbidities, and perspectives. As PWN have varying needs, clinicians should consider a more personalized approach to therapy, including active participation of PWN in their care and shared decision-making between patient and clinician to achieve optimal outcomes. In this review, we discuss the various characteristics and challenges of PWN, present illustrative clinical case scenarios of PWN, provide clinicians with a proposed framework to best address therapy for PWN, and demystify concerns with sodium oxybate.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"71-83"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668869","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":"Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review.","authors":"Frank M C Besag, Michael J Vasey, Sulagna Roy, Samuele Cortese","doi":"10.1007/s40263-024-01154-4","DOIUrl":"10.1007/s40263-024-01154-4","url":null,"abstract":"<p><strong>Background: </strong>Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature. The aim of this review is to evaluate the evidence in the published literature for Raynaud syndrome associated with medication for ADHD.</p><p><strong>Methods: </strong>We systematically searched PubMed and Embase from inception to 12 June 2024 for articles published in English describing cases of RS in individuals treated with stimulant medication, atomoxetine, guanfacine or clonidine. Identified cases were assessed against the Naranjo Adverse Drug Reaction Scale criteria to determine the probability of a causal relationship with the medication.</p><p><strong>Results: </strong>The initial search identified 197 articles. A total of 61 cases were identified from 15 case reports, 5 case series, 1 retrospective case-control study, and 1 retrospective cohort study. No randomised, controlled studies were identified. Implicated medications included methylphenidate, (dex)amfetamine and, more rarely, atomoxetine. Most cases were mild and resolved within weeks of discontinuation, dose reduction or switch to an alternative medication. A few cases associated with systemic disease were reported, leading to ulceration, gangrene and the need for amputation or revascularisation in some individuals. Assessment of 28 cases using the Naranjo criteria suggested a 'possible' causative role of ADHD medication in 13 cases, a 'probable' role in 13 cases and a 'definite' role in two cases.</p><p><strong>Conclusions: </strong>Due to the uncontrolled nature of all but one of the available studies, a causal relationship between medication for ADHD and RS could not be determined reliably. However, in view of the possibility of severe sequelae, albeit in rare cases, routine monitoring for signs of RS is recommended in individuals treated with CNS stimulants or atomoxetine, especially when initiating treatment or increasing the dose. Large database studies in which individuals act as their own controls should be conducted to clarify any association between treatment with these medications and RS, controlling for confounding factors.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"213-241"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058231","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":"Assessing Early Efficacy After Initiation of Once-Nightly Sodium Oxybate (ON-SXB; FT218) in Participants with Narcolepsy Type 1 or 2: A Post Hoc Analysis from the Phase 3 REST-ON Trial.","authors":"Lois Krahn, Asim Roy, John W Winkelman, Anne Marie Morse, Jennifer Gudeman","doi":"10.1007/s40263-024-01143-7","DOIUrl":"10.1007/s40263-024-01143-7","url":null,"abstract":"<p><strong>Background: </strong>Once-nightly sodium oxybate (LUMRYZ™; ON-SXB; FT218) significantly improved narcolepsy symptoms in the phase 3 REST-ON trial. The objective of this post hoc analysis was to investigate the early efficacy of ON-SXB at weeks 1 (4.5-g dose) and 2 (6-g dose).</p><p><strong>Methods: </strong>In REST-ON, participants (≥ 16 years) with narcolepsy type 1 or 2 were randomized 1:1 to ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or placebo. Protocol-prespecified efficacy assessments were conducted at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose). A post hoc analysis was conducted to assess the early efficacy of ON-SXB, defined as efficacy at weeks 1 (4.5-g dose) and 2 (6-g dose) on Epworth Sleepiness Scale (ESS) score, visual analog scale (VAS) sleep quality, and VAS refreshing nature of sleep. Least squares mean differences (LSMD) in change from baseline to weeks 1 and 2, 95% confidence intervals (CIs), and P values were calculated using mixed-effects models for repeated measures.</p><p><strong>Results: </strong>In the modified intent-to-treat population (n = 190; ON-SXB, n = 97; placebo, n = 93), baseline ESS scores were 16.6 and 17.5, sleep quality scores were 53.8 and 55.9, and refreshing nature of sleep scores were 46.5 and 49.9 with ON-SXB and placebo, respectively. At week 1 (4.5 g), numerical improvement in ESS score (LSMD [95% CI], - 0.7 [- 1.6 to 0.2]) and significant improvements in sleep quality (3.6 [1.1-6.1]; P < 0.01) and refreshing nature of sleep (3.2 [0.5-5.9]; P < 0.05) were observed with ON-SXB versus placebo. At week 2 (6 g), significant improvements with ON-SXB versus placebo were observed for ESS score (- 1.3 [- 2.4 to - 0.2]; P < 0.02), sleep quality (7.0 [3.8-10.1]; P < 0.001), and refreshing nature of sleep (5.8 [2.3-9.4]; P = 0.001).</p><p><strong>Conclusions: </strong>ON-SXB improved daytime sleepiness, sleep quality, and refreshing nature of sleep, with observable benefits beginning in the first week of treatment. These data may help clinicians set expectations with patients.</p><p><strong>Clinical trial id: </strong>NCT02720744.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"53-59"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669409","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":"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":"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":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>This post hoc analysis was conducted to evaluate safety and efficacy among participants who received high-dosage deutetrabenazine treatment (> 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.</p><p><strong>Methods: </strong>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 > 48 mg/d), and total maximal chorea (TMC) scores were analyzed by cohort during the stable-dose period.</p><p><strong>Results: </strong>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 > 48 mg/d (exposure = 74.1 person-years). Similar results were found among the subset of participants who received deutetrabenazine dosages > 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 > 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.</p><p><strong>Conclusions: </strong>In this open-label, long-term study, some participants received deutetrabenazine dosing > 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 > 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.</p><p><strong>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}