CNS drugs最新文献

{"title":"Peripheral Immune-Inflammatory Pathways in Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: Exploring Their Potential as Treatment Targets.","authors":"Abbas F Almulla, Michael Maes","doi":"10.1007/s40263-025-01195-3","DOIUrl":"10.1007/s40263-025-01195-3","url":null,"abstract":"<p><p>Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are major mental disorders linked to substantial morbidity. Traditional monoamine-based pharmacotherapies frequently produce inadequate outcomes for many patients. The elevated levels of treatment resistance require the exploration of new pharmacological targets. Evidence indicates that peripheral immune-inflammatory dysregulation, characterized by an imbalance between immunological responses and compensatory immune-regulatory systems (IRS/CIRS), together with increased oxidative and nitrosative stress (O&NS), significantly contributes to the pathogenesis of these disorders. This review examines IRS/CIRS/O&NS pathways as new drug targets and highlights novel pharmacological trials. Antiinflammatory drugs have been repurposed as augmentation strategies for the treatment of MDD/BD and SCZ, including nonsteroidal antiinflammatory medications, such as cyclooxygenase-2 (COX-2) inhibitors; cytokine-targeting biologics, such as tumor necrosis factor-α monoclonal antibodies; and minocycline, an antibiotic that attenuates neuroinflammation. N-acetylcysteine, curcumin, and omega-3 polyunsaturated fatty acids demonstrate some efficacy as augmentation therapies in MDD, likely by diminishing IRS activation and O&NS. Strategies aimed at the gut-brain axis and gut dysbiosis, including fecal microbiota transplantation, are under investigation for their capacity to restore immunological homeostasis by improving gut barrier integrity and microbiome composition. This review examines new potential therapeutic targets arising from recent discoveries in neuro-immune interactions and oxidative stress, including particular lymphocyte surface markers, the CIRS, and intracellular network molecules in both affective and psychotic disorders. The evidence underscores the clinical importance of immune-targeted augmentation treatments in psychiatric disorders and supports the ongoing development of these novel pharmacotherapies within a precision medicine paradigm.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"739-762"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293420","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":"Pharmacokinetics and Pharmacodynamics of Intranasal Diacetylmorphine in Heroin-Assisted Treatment for Severe Opioid Use Disorder.","authors":"Adrian Guessoum, Severin B Vogt, Maximilian Meyer, Jean Nicolas Westenberg, Benjamin Klemperer, Kenneth M Dürsteler, Matthias E Liechti, Jan Thomann, Dino Luethi, Urs Duthaler, Marc Vogel","doi":"10.1007/s40263-025-01189-1","DOIUrl":"10.1007/s40263-025-01189-1","url":null,"abstract":"<p><strong>Background: </strong>Intranasal diacetylmorphine (IN DAM) represents a promising new route of administration, which is currently under investigation as a novel treatment approach for opioid use disorder in Switzerland. This study characterized the pharmacokinetics and pharmacodynamics of therapeutically relevant intranasal doses of DAM and its metabolites in patients with severe opioid use disorder.</p><p><strong>Methods: </strong>In this prospective observational study, patients on intranasal heroin-assisted treatment (HAT) in Basel, Switzerland, self-administered their usual dose of IN DAM before receiving their daily maintenance dose. Inclusion criteria were age ≥ 18 years and current participation in IN HAT. Plasma concentrations of diacetylmorphine, 6-monoacetylmorphine (6-MAM), morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured using liquid chromatography-tandem mass spectrometry at baseline and at 2, 5, 10, 15, 20, 30, 40, 50, 60, 120, and 180 min. Acute subjective effects and cravings were assessed repeatedly using visual analog scales, withdrawal symptoms were measured using the Short Opiate Withdrawal Scale, and autonomic responses were recorded over the 3 h after IN DAM administration.</p><p><strong>Results: </strong>In total, 14 patients were included in the study. The mean self-administered IN DAM dose was 346 mg (range 190-700 mg) delivered over a mean time of 3.8 min (range 1-9 min). IN DAM elicited moderate-to-strong peak drug effects, with marked reductions in heroin craving and withdrawal symptoms. No clinically relevant respiratory depression or decrease in oxygenation saturation was observed. Subjective effects occurred rapidly within the first 2 min after the start of administration. These effects gradually increased and peaked at 30-35 min, which paralleled the rising plasma concentrations of DAM and 6-MAM, while the sustained heroin-like effects best correlated with morphine and morphine-6-glucuronide plasma concentrations. Plasma half-lives of diacetylmorphine and 6-monoacetylmorphine were longer, and time to maximal plasma concentration was later than previously reported, suggesting saturated absorption at high intranasal doses and volumes.</p><p><strong>Conclusions: </strong>IN DAM has a good safety profile and should be considered as an effective alternative for patients in HAT, offering rapid onset of effects without significant side effects. Optimization of intranasal delivery may further improve absorption and clinical utility.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"807-817"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246800","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":"Subclinical Augmentation in Relation to Previous Dopaminergic Treatment in Patients with Restless Legs Syndrome: A Post Hoc Analysis of Two Randomized, Placebo-Controlled, Crossover Trials.","authors":"Diego Garcia-Borreguero, David Anguizola, Catalina Carvallo, Alejandro Lopez, Alba Garcia Aragón, Brian Moncada, Sergi Ferré","doi":"10.1007/s40263-025-01192-6","DOIUrl":"10.1007/s40263-025-01192-6","url":null,"abstract":"<p><strong>Background and objectives: </strong>Augmentation, a long-term complication of dopamine agonist treatment for restless legs syndrome (RLS), is preceded by a gradual loss of response. We investigated whether prior long-term dopaminergic treatment affects current and future responses to dopaminergic and non-dopaminergic drugs, which would suggest broader changes in RLS pathophysiology.</p><p><strong>Methods: </strong>We retrospectively analysed two previously published, double-blind, randomized, crossover, placebo-controlled studies with the adenosine transport inhibitor dipyridamole and the orexin receptor antagonist suvorexant. Post hoc analyses compared responses between dopaminergic (DA)-naïve and dopaminergic (DA)-treated patients with RLS. None of these patients met the diagnostic criteria for augmentation. After a 2-week washout, patients received active treatment (10-20 mg suvorexant or 200-300 mg dipyridamole) or placebo for 2 weeks, followed by crossover. Efficacy was assessed using the International RLS Rating Scale (IRLS), Clinical Global Impressions-Severity scale (CGI-S), multiple suggested immobilization test (m-SIT), periodic leg movements of sleep (PLMS) and other polysomnographic measures.</p><p><strong>Results: </strong>A total of 28 patients participated in the dipyridamole study (DA-pretreated, n = 10; DA-naïve group, n = 18), and 40 participated in the suvorexant study (DA-pretreated, n = 9; DA-naïve group, n = 31). Compared with DA-naïve patients, DA-pretreated patients responded significantly worse to both treatments on the basis of the IRLS, CGI-S, m-SIT, PLMS indices. There were no differences in sleep parameters.</p><p><strong>Conclusions: </strong>Our results suggest that previous long-term dopaminergic treatment, even before clinical augmentation is reached, induces pathophysiological changes in RLS that impair future responses to both dopaminergic and non-dopaminergic therapies. Our findings confirm previous results with gabapentin enacarbil and suggest that these changes develop well before clinical augmentation appears. Pathophysiological implications for the understanding of dopaminergic augmentation are discussed. Our results support the American Academy of Sleep Medicine (AASM) recommendation against using dopamine agonists as the initial choice for RLS treatment.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"779-793"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224591","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":"Investigational Gene Therapies for Parkinson's Disease.","authors":"Nicolas Phielipp, Claire Henchcliffe","doi":"10.1007/s40263-025-01203-6","DOIUrl":"10.1007/s40263-025-01203-6","url":null,"abstract":"<p><p>Since the publication of the first gene therapy clinical trial in Parkinson's disease (PD) in 2007, rapid advances have resulted in escalating interest in applying this technology to manipulate various cellular processes altered in PD. There is now a rich literature describing the various approaches taken, including modulating aberrant networks, restoring dopamine, and mitigating deleterious effects of known gene mutations or as a restorative therapy. Evidence has accrued supporting feasibility, safety, and tolerability of initial gene therapy approaches, as well as providing initial indications of efficacy in several cases. However, there have also been unexpected challenges, and technology is still evolving, making this an important time point to evaluate what has been learned and to place it in context to support ongoing and future efforts. In this review, we focus on the potential of gene therapy to ameliorate symptoms and modify disease progression in PD. We critically review previous clinical research, we address potential benefits and predicted limitations, and we address pipeline approaches aiming to bring a gene therapy approach to the clinic.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"725-737"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607672","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":"Efficacy and Safety of Once-Monthly Paliperidone Palmitate Long-Acting Injections in Chinese Patients with Early-, Mid-, and Late-Phase Schizophrenia: A Post-Hoc Analysis of Three Phase 4 Studies.","authors":"Qian Li, Yang Li, Yishen Yang, Jianmin Zhuo, Miaomiao Jia, Chong Ye, Tianmei Si","doi":"10.1007/s40263-025-01194-4","DOIUrl":"10.1007/s40263-025-01194-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Long-acting injectable (LAI) antipsychotics have improved treatment adherence and continuity compared with oral antipsychotics. However, evidence gaps persist in the endorsement of LAIs for early-phase schizophrenia in China. This post-hoc analysis evaluated the efficacy and safety of once-monthly paliperidone palmitate (PP1M), an LAI antipsychotic, following early-, mid-, and late-phase use in Chinese patients with schizophrenia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data from three phase 4 studies (NCT01527305, NCT01947803, and NCT01685931) were used. Chinese patients with schizophrenia (disease duration early: ≤ 2 years; mid: &gt; 2 to ≤ 5 years; late: &gt; 5 years) who received 13 weeks of PP1M treatment were included. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 13, and the secondary and exploratory endpoints included change in Clinical Global Impression of Severity scale (CGI-S), PANSS responder rate relative to baseline PANSS total scores (≤ 70, 70-90 [exclusive], and ≥ 90), and treatment-emergent adverse events (TEAEs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 1053 patients (early: 383; mid: 290; late: 380) were included. Following PP1M, improvements in efficacy outcomes were observed in all phases of schizophrenia including PANSS total score from baseline to week 13 (least square [LS]-mean change early: - 31.6; mid: - 28.4; late: - 25.6; p = 0.0003 across three groups) and CGI-S (median reduction early: - 2.0; mid: - 1.0; late: - 1.0). The greatest improvements in efficacy outcomes were consistently seen in early-phase patients, indicated by differences in PANSS total score (baseline to week 13 LS-mean differences mid versus early: 3.2 [p = 0.2175], late versus mid: 2.8 [p = 0.2783], and late versus early: 6.0 [p = 0.0011]), and nominal significant differences in CGI-S (mid versus early: p = 0.0015 and late versus early: p = 0.0180). Earlier administration of PP1M results in greater efficacy outcomes regardless of the initial disease severity. For patients with a PANSS score ≤ 70 at baseline, reductions of ≥ 30% were observed in 71.4%, 60.0%, and 50.0% (p = 0.0003 across three groups), and for patients with a PANSS score ≥ 90 at baseline, reductions of ≥ 30% were observed in 76.4%, 72.5%, and 69.6% (p = 0.0003 across three groups) of patients in the early-, mid-, and late-phase, respectively. The proportion of patients experiencing ≥ 1 TEAE (early: 44.3%; mid: 38.4%; late: 39.8%) was numerically higher in the early phase. Incidences of serious TEAEs (early: 2.8%; mid: 4.0%; late: 4.2%) and TEAEs leading to death (early: 0.3%; mid: 0.0%; late: 1.6%) were observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Treatment with PP1M improves efficacy outcomes in Chinese adult patients with schizophrenia. However, when PP1M was used in earlier phases of schizophrenia, consistently greater improvements in efficacy outcomes were observed compared with later phases, r","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"795-805"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301262","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":"Management of Bipolar Disorder in Pregnancy and Postpartum: A Clinicians' Guide.","authors":"Veerle Bergink, Mariella Suleiman, Mary-Anne Hennen, Thalia Robakis","doi":"10.1007/s40263-025-01202-7","DOIUrl":"10.1007/s40263-025-01202-7","url":null,"abstract":"<p><p>Medication management in women with bipolar disorder (BD) in the perinatal period is challenging, given that many patients taper or stop medication during pregnancy, and the postpartum period is an extremely high-risk period for relapse. The objective of this narrative review was to investigate the perinatal efficacy as well as potential adverse effects on the child of common treatments for bipolar disorder. These treatments include lithium, lamotrigine, other antiepileptics, quetiapine, olanzapine, aripiprazole, other antipsychotics, antidepressants, benzodiazepines, Z-drugs, and other sleep medication. Despite the worldwide decline in lithium use, it remains the gold standard for acute and maintenance treatment of BD, and we continue to advise its use in women of reproductive age. In contrast, medications with a high risk for teratogenicity such as valproate and carbamazepine should be avoided in women of childbearing potential. Women with bipolar disorder are at very high risk of relapse after delivery, but this risk is more than twofold lower with adequate pharmacological prophylaxis. We advise to make a written perinatal bipolar relapse prevention plan in collaboration with the patient, family, and healthcare professionals, which includes a description of: (1) maintenance treatment during pregnancy, (2) preferred mode of delivery, (3) medication immediately after delivery and the first months postpartum for relapse prevention, (4) preferred plan for feeding (breast-feeding versus bottle-feeding), (5) strategies to assist women in ensuring adequate sleep and stable circadian rhythm in the first weeks after delivery, and (6) how to recognize the first symptoms of relapse and which intervention strategies to take.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"763-777"},"PeriodicalIF":7.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539296","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":"Strategies for Switching between Oral Postsynaptic Antidopaminergic Antipsychotics in Patients with Schizophrenia: A Systematic Review.","authors":"Christoph U Correll","doi":"10.1007/s40263-025-01206-3","DOIUrl":"https://doi.org/10.1007/s40263-025-01206-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Antipsychotic switching is common in the treatment of schizophrenia. Pharmacokinetic and pharmacodynamic properties of antipsychotics can inform switch strategies, as switching from shorter to longer half-life antipsychotics and switching from more antagonistic to less antagonistic or partial agonist agents at dopaminergic, histaminergic, and cholinergic receptors can lead to withdrawal or rebound symptoms, potentially complicating switch results. This systematic literature review of studies investigated switching strategies between oral antipsychotics. Pharmacokinetic and pharmacodynamic characteristics of antipsychotics that can influence switch outcomes were also extracted from publications and prescribing information.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PubMed databases were queried (last search 13 May 2024) for articles published from 1 June 2010 to 1 April 2024, with keywords (schizophr* OR schizoaff*) AND (antipsychotic*) AND (switch*). Randomized controlled trials, open-label studies, meta-analyses, and reviews of oral antipsychotic switching were included. Records were excluded if they investigated a disease other than schizophrenia or schizoaffective disorder or focused on long-acting injectable or non-approved antipsychotics. Data on switch strategies investigated and study outcomes were manually extracted from randomized controlled trials and open-label switch studies of oral antipsychotics in schizophrenia or schizoaffective disorder. Meta-analyses and review articles were summarized. There was no assessment for risk of bias or specific method to synthesize results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the 579 records identified during the systematic review, 80 articles investigated switching of oral antipsychotics in adult patients with schizophrenia, including 58 randomized and non-randomized studies (9 of which investigated ≥ 1 antipsychotic) and 22 review articles or meta-analyses. The antipsychotics investigated during this period were: aripiprazole (studies = 18); paliperidone, ziprasidone, olanzapine, and risperidone (studies = 7 each); brexpiprazole, clozapine and lurasidone (studies = 4 each); amisulpride, (studies = 3); quetiapine and iloperidone (studies = 2 each); and asenapine and lumateperone (1 study each). Most studies that reported a switch method employed cross-titration switching (studies = 39; 69.6%), while abrupt switching (studies = 10; 17.9%) and switching at investigator's discretion (studies = 7; 12.5%) were rare. A total of 24 studies (N = 3440 patients) had statistical comparisons between treatment groups, but few studies specifically statistically compared outcomes between different switch strategies (1 trial each for aripiprazole, clozapine, iloperidone, and ziprasidone; N = 666 patients), with mixed outcomes. Frequencies of sedative rescue treatments, which could have attenuated potential withdrawal symptoms, w","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689108","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":"Barriers to Safely Discontinuing Duloxetine: An Urgent Call to Action.","authors":"Bryan Shapiro, Daniel Cohrs","doi":"10.1007/s40263-025-01208-1","DOIUrl":"https://doi.org/10.1007/s40263-025-01208-1","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667346","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 Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial.","authors":"Alpesh Shah, Alvin Estilo, Pamela L Sheridan, Uwa Kalu, Dalei Chen, Denise Chang, Mary Slomkowski, Daniel Lee, Nanco Hefting, Mary Hobart, Saloni Behl, Pedro Such, Malaak Brubaker, George T Grossberg","doi":"10.1007/s40263-025-01200-9","DOIUrl":"https://doi.org/10.1007/s40263-025-01200-9","url":null,"abstract":"<p><strong>Background and objective: </strong>Older adults with dementia are particularly vulnerable to antipsychotic side effects. Brexpiprazole, an atypical antipsychotic, is approved in a number of countries for the treatment of agitation associated with dementia due to Alzheimer's disease. This pooled analysis aimed to evaluate the safety and tolerability of brexpiprazole in this patient population.</p><p><strong>Methods: </strong>Data were included from three Phase 3, 12-week, randomized, double-blind, placebo-controlled trials and a Phase 3, 12-week, active-treatment extension trial in participants with agitation associated with dementia due to Alzheimer's disease. Safety outcomes included treatment-emergent adverse events (TEAEs), weight change, suicidality, extrapyramidal symptoms, and cognitive dysfunction. Two datasets were considered: a 12-week dataset that pooled data from the three randomized trials for brexpiprazole 0.5-3 mg/day and placebo, and a 24-week dataset that combined data from the parent randomized trial and the extension trial for brexpiprazole 2-3 mg/day.</p><p><strong>Results: </strong>Over 12 weeks, 335/655 (51.1%) participants on brexpiprazole and 178/388 (45.9%) participants on placebo reported ≥ 1 TEAE, which led to discontinuation in 41 (6.3%) and 13 (3.4%) participants, respectively. Headache was the only TEAE with incidence ≥ 5% (brexpiprazole, 50 [7.6%] participants; placebo, 36 [9.3%] participants). The incidences of cerebrovascular TEAEs (brexpiprazole, 0.5%; placebo, 0.3%), cardiovascular TEAEs (3.7%; 2.3%), extrapyramidal symptom-related TEAEs (5.3%; 3.1%), and somnolence/sedation TEAEs (3.7%; 1.8%) were generally similar between treatment groups. Six (0.9%) participants on brexpiprazole and 1 (0.3%) participant on placebo died; causes of death were not considered related to brexpiprazole and were generally in line with those expected in Alzheimer's disease. Over 24 weeks, 110/226 (48.7%) participants on brexpiprazole reported ≥ 1 TEAE, which led to discontinuation in 19 (8.4%) participants. Headache was the only TEAE with incidence ≥ 5% (18 [8.0%] participants). No participants died during the extension trial. Over 12 and 24 weeks, mean changes in weight, suicidality, and extrapyramidal symptoms were minimal, with no worsening of cognition.</p><p><strong>Conclusions: </strong>Considering pooled data from > 1000 participants on brexpiprazole or placebo, brexpiprazole appears to be generally well tolerated for up to 24 weeks in participants with agitation associated with dementia due to Alzheimer's disease.</p><p><strong>Study registration: </strong>ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584, NCT03594123.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667347","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":"Multiple Sclerosis in People of Diverse Racial and Ethnic Backgrounds: Presentation, Disease Course, and Interactions with Disease-Modifying Therapy.","authors":"Julia Li, Nandita Vas, Lilyana Amezcua, Dalia L Rotstein","doi":"10.1007/s40263-025-01205-4","DOIUrl":"https://doi.org/10.1007/s40263-025-01205-4","url":null,"abstract":"<p><p>Multiple sclerosis (MS) affects people of all racial and ethnic backgrounds, with greatest prevalence noted in Black and white individuals living in Europe and North America. Age of MS onset seems to be earlier in Black, Latino/Hispanic, and South Asian people living with MS in North America and the United Kingdom. Additionally, Black and Latino/Hispanic people with MS in the USA are more likely to have severe initial presentations and earlier accumulation of disability compared with white people with MS. Evidence is sparse concerning how efficacy and safety of disease-modifying therapies for MS may vary with race and ethnicity, largely due to underrepresentation of racial and ethnic diversity in clinical trials. Social determinants of health such as sex, income, education, and the built environment interact with race and ethnicity to affect delays in MS diagnosis, use of therapy, and disease outcomes. In general, considering earlier disability progression, barriers to treatment access and adherence, and existing drug efficacy data, there may be even greater reason to consider early high efficacy therapy in underrepresented populations. More research and targeted interventions are needed to improve outcomes for people of diverse racial and ethnic backgrounds living with MS.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658550","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}