CNS drugs最新文献

{"title":"Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.","authors":"Savannah E Quigley, Kellen H Quigg, Stephen A Goutman","doi":"10.1007/s40263-025-01217-0","DOIUrl":"10.1007/s40263-025-01217-0","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons. ALS is classically characterized by painless progressive weakness, causing impaired function of limbs, speech, swallowing, and respiratory function. The disease is fatal within 2-4 years, often the result of respiratory failure. The pathologic hallmark for a majority of ALS cases is aberrant cytoplasmic accumulations of the nuclear protein TAR-DNA binding protein (TDP-43). A total of 10-15% of ALS can be attributed to a single gene mutation, known as genetic or \"familial\" ALS, while the remainder of cases are termed nongenetic or \"sporadic\" although heritability has been measured in up to 37% in this population. Complex interactions between genetics, environment, and physiologic susceptibility are thought to contribute to disease. Management is primarily supportive in nature, though there are several approved treatments worldwide. This review details the mechanisms and evidence of approved disease-modifying treatments, relevant measures to track disease burden and progression used in clinical trials, and approaches to pharmacologic management of common symptoms in ALS. As there is not currently a cure for ALS, research into the complex pathophysiologic and genetic alterations contributing to disease is of great interest. This review further discusses the current understanding of genetic etiologies and altered physiology leading to disease, such as neuroinflammation, integrated stress response, aberrant proteostasis and mitochondrial dysfunction, among others. The translation of preclinical discoveries into current investigational therapeutics, novel therapeutic categories such as antisense oligonucleotides and stem cell transplantation, as well as future horizons harnessing the power of artificial intelligence in drug development and clinical trials are discussed.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"949-993"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945578","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":"Antipsychotic-Related Prolactin Changes: A Systematic Review and Dose-Response Meta-analysis.","authors":"Xiao Lin, Spyridon Siafis, Jing Tian, Hui Wu, Mengchang Qin, Christoph U Correll, Johannes Schneider-Thoma, Stefan Leucht","doi":"10.1007/s40263-025-01218-z","DOIUrl":"10.1007/s40263-025-01218-z","url":null,"abstract":"<p><strong>Background: </strong>Prolactin increase is a common and potentially problematic adverse event of antipsychotics. We aimed to discover the relationship between antipsychotic doses and changes in prolactin levels.</p><p><strong>Objective: </strong>To examine the relationship between antipsychotic doses and changes in prolactin levels in adults with acutely exacerbated schizophrenia.</p><p><strong>Methods: </strong>We searched the Cochrane Schizophrenia Group register (last search 26 July 2024) and previous reviews for fixed-dose, randomized controlled trials (RCTs) that investigated monotherapy of 21 antipsychotics in adults with acutely exacerbated schizophrenia. The primary outcome was mean prolactin change from baseline to study endpoint adopting mean differences (MD) in ng/mL as the effect size measure. The dose-response curves were estimated by conducting random-effects dose-response meta-analyses using the restricted cubic spline method.</p><p><strong>Results: </strong>Among 165 eligible studies, 68 studies with 238 dose arms (23,128 participants, 35% female) reported on prolactin and were meta-analyzed. Of these, 94% lasted ≤ 3 months, and 90% of the studies used oral formulations. Participants in one study experienced their first episode, while all other studies also included multiepisode participants. The dose-response curves indicated that with aripiprazole, higher doses were significantly associated with lower prolactin levels than lower doses. Brexpiprazole, cariprazine, lumateperone, and quetiapine carried negligible risks for prolactin increase across examined doses. During treatment with most other antipsychotics, i.e., asenapine, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, risperidone, and ziprasidone, prolactin levels rose with increasing doses and then continued to increase or plateaued. The shape of the dose-response curves was similar in males and females, with generally larger amplitudes of the curves in females.</p><p><strong>Conclusions: </strong>The prolactin-increasing property varies among antipsychotics, is dose-related, and is greater in females. These findings in adults with acutely exacerbated schizophrenia can help clinicians titrate and adapt antipsychotic doses and consider patients' sex in treatment decisions. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration no. CRD42020181467.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"937-947"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882351","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":"Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials.","authors":"Nicola Specchio, Stéphane Auvin, Teresa Greco, Lieven Lagae, Charlotte Nortvedt, Sameer M Zuberi","doi":"10.1007/s40263-025-01201-8","DOIUrl":"10.1007/s40263-025-01201-8","url":null,"abstract":"<p><strong>Background and objective: </strong>In clinical trials of patients with Lennox-Gastaut syndrome (LGS), a ≥ 50% reduction in drop seizure frequency is generally accepted as a key endpoint. However, smaller reductions (< 50%) may yet be impactful for patients in real-world settings. This exploratory analysis evaluated the threshold for a clinically important response in drop seizures that is associated with the Caregiver Global Impression of Change (CGIC) scale score in patients with LGS treated with cannabidiol (CBD) oral solution and assessed the suitability of CGIC as an anchor for meaningful change.</p><p><strong>Methods: </strong>This exploratory post hoc analysis included patients with LGS (N = 215, age 2-55 years) receiving CBD (Epidiolex^® [USA]/Epidyolex^® [EU]; 100 mg/mL oral solution) in two phase 3 randomized placebo-controlled trials (NCT02224690, April-October 2015, and NCT02224560, June- December 2015). Reduction in drop seizures (involving sudden loss of muscle tone) was anchored to CGIC scores of \"slightly improved\" or better or \"much improved\" or better, to determine the threshold at which seizure reduction can be considered clinically meaningful to patients. Spearman's correlation indicated suitability of anchors (absolute value ≥ 0.30 deemed appropriate).</p><p><strong>Results: </strong>In the 215 patients receiving CBD with a CGIC score recorded, CGIC was \"slightly improved\" or better in 60% of patients, and \"much improved\" or better in 31% after 14 weeks of treatment. With a CGIC rating of \"slightly improved\" or better, the best threshold for a clinically important response in drop seizure reduction was - 30.6% (57.7% of patients). Mean and median percentage reductions in drop seizures were - 46.9% and - 58.6%, respectively. Using \"much improved\" or better, the best threshold was - 49.6% (40.5% of patients). Mean and median percentage reductions in drop seizures were - 57.6% and - 66.0%, respectively. Spearman's correlation was 0.47.</p><p><strong>Conclusion: </strong>Anchoring to CGIC of \"slightly improved\" or better, the threshold for a clinically meaningful reduction in drop seizure frequency was 31%, suggesting that a 50% cutoff may overlook patients with meaningful improvements in their overall condition, as perceived by their caregivers. CGIC scores, although potentially less nuanced than other standardized clinical assessments, were appropriate anchors to determine thresholds. This exploratory analysis may help contextualize clinical trial data to better understand potential patient benefit attained by reductions in drop seizure frequency observed in real-world settings that are < 50%.</p><p><strong>Clinical trials registration numbers: </strong>NCT02224560 and NCT02224690.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1025-1036"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798372","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":"Nonseizure Outcomes in Dravet Syndrome: Potential Impact of Pharmacotherapy.","authors":"Adriana Swindler, Alexander Harper, Kirsty Hendry, Adam Strzelczyk, Colin Reilly, Andreas Brunklaus","doi":"10.1007/s40263-025-01212-5","DOIUrl":"10.1007/s40263-025-01212-5","url":null,"abstract":"<p><p>Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by drug-resistant seizures and multiple nonseizure comorbidities. While disease management has mainly focused on seizure control, there is growing recognition of the importance of nonseizure outcomes in treatment evaluation. This review examines evidence for treatment effects on key nonseizure domains including cognitive functioning, adaptive behavior, speech and language, neurobehavior, sleep, motor outcomes, orthopedic sequelae, nutrition/growth, and quality of life. There is limited evidence following anti-seizure medication trials suggesting improvements in executive function, particularly in preschool-aged children, though findings are inconsistent across studies. Sodium channel blockers are contraindicated, with evidence linking their use to cognitive decline and reduced quality of life. For neurobehavioral symptoms, pharmacological and nonpharmacological treatments show promise in reducing ADHD and behavioral difficulties. Sleep disturbances affect most patients, but evidence for melatonin efficacy is limited. Motor impairments are common, including delayed development, gait abnormalities, and decreased mobility and limited evidence suggests improvements with pharmacological treatment for parkinsonian symptoms. Orthopedic complications include scoliosis, while feeding difficulties may necessitate gastrostomy tube placement. Quality of life measures indicate significant impact from nonseizure symptoms, with evidence of improvement with anti-seizure medication treatment. Overall, findings are limited by small sample sizes, heterogeneous outcome measures, and over-reliance on caregiver reporting. There is a significant knowledge gap regarding disease comorbidities, and future research should investigate nonseizure outcomes alongside seizure control in interventional studies. Dravet syndrome research will benefit from the development of standardized tools validated in the DS population, and establish a core set of outcome measures, prioritized by families, clinicians and researchers to enable meaningful comparison across studies.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"995-1009"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945553","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":"Effectiveness and Tolerability of Vortioxetine Oral Drops Versus Oral Tablets in Major Depressive Disorder: An Analysis of a Real-World Cohort Study in Switzerland.","authors":"Barbara Hochstrasser, Gregor Hasler, Axel Baumann, Rohini Bose, Elin Reines, Martin Kammerer, Alexandra Sousek","doi":"10.1007/s40263-025-01207-2","DOIUrl":"10.1007/s40263-025-01207-2","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and tolerability of vortioxetine tablets for depression is established, but prospective data for the oral drop formulation were unavailable. This analysis compared the effectiveness, tolerability and dosing patterns of vortioxetine tablet and drop formulations for the treatment of major depressive episodes in Swiss real-world practice.</p><p><strong>Methods: </strong>A post hoc analysis of a prospective, non-interventional study in adults experiencing a major depressive episode (MDE) was conducted. Depression symptoms, functioning, dosing patterns and tolerability were assessed using unanchored Montgomery-Åsberg Depression Rating Scale items, the Clinical Global Impression-Severity (CGI-S) scale, a four-point functioning scale, and incidence of adverse drug reactions (ADRs). Statistical tests included two-sample t-tests, Fisher's exact test, Chi-square test and general linear modelling.</p><p><strong>Results: </strong>Of 225 patients, 60 (26.7%) initiated drops. Drops were more often prescribed for first MDE than tablets (65.0% [n = 39] versus 46.1% [n = 76]; p = 0.012) and shorter MDE duration at baseline (2.9 versus 4.8 months; p = 0.02). Mean CGI-S baseline scores were similar (drops: 5.0; tablets: 4.8). Both formulations improved depressive symptoms and functioning similarly. Drops were used in lower initial doses (4.2 mg/day) versus tablets (7.7 mg/day) (p < 0.001) but in higher doses (> 10 mg/day) earlier during treatment (35% versus 13%, day 15). 'No or little effect' was significantly less frequent with drops (5.0%; n = 3) versus tablets (23.6%; n = 39) (p < 0.001). ADR-related discontinuations were comparable (drops: 3.3%; tablets: 4.2%).</p><p><strong>Conclusions: </strong>This real-world analysis suggests that vortioxetine drops provide comparable control of depressive symptoms to tablets. The greater capacity for dose individualisation may be beneficial to patients.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1047-1059"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728385","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":"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":"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":"1011-1023"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423206/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Antiseizure Medications on Lipid Profile and Weight in Patients with Epilepsy: A Systematic Review with Meta-analysis.","authors":"Paweł Chochoł, Natalia Arturo, Paweł Marek Łajczak, Aisha Rizwan Ahmed, Aishwarya Koppanatham, Thomas C Varkey","doi":"10.1007/s40263-025-01231-2","DOIUrl":"https://doi.org/10.1007/s40263-025-01231-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Antiseizure medications (ASMs) are often taken long term by patients with epilepsy yet may be associated with differing metabolic and cardiovascular risks, including hyperlipidemia and weight changes. This systematic review and meta-analysis evaluated the effects of individual ASMs on lipid profiles and weight changes in patients with epilepsy. This paper also provides detailed insights into safety profiles across different patient subgroups and the impact of treatment duration, which was previously underrepresented in individual studies that showed conflicting results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed, Scopus, and Cochrane Central databases were searched from inception until June 2024 for studies reporting lipid derangements after ≥ 3 months of ASM monotherapy in patients with epilepsy in comparison with healthy controls. Primary outcomes were total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels. Secondary endpoints were high-density lipoprotein cholesterol, triglycerides, and body mass index (BMI). Mean difference (MD) and standardized mean difference (SMD) were computed using a random-effects model. Further subgroup analyses were performed for adult and pediatric populations, as well as for the duration of treatment, and sensitivity, when feasible.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 28 studies, totaling 2231 patients and 1582 healthy controls, were included in this meta-analysis. Significant TC and LDL alterations were observed soon after introducing carbamazepine {TC SMD 1.23 [95% confidence interval (CI) 0.93-1.54]; LDL SMD 1.00 [95% CI 0.70-1.30]} and oxcarbazepine [TC SMD 1.0 (95% CI 0.67-1.34)] in all patient subgroups, as well as phenytoin [TC 0.72 (95% CI 0.37-1.06); LDL SMD 0.41 (95% CI 0.03-0.79)] and valproate in long-term therapy in adult patients. Lamotrigine reduces LDL levels over time [MD - 5.15 (95% CI - 9.51 to - 0.80)] in adults. Levetiracetam has a neutral effect on lipid profile. BMI increases on valproate treatment in the pediatric population [MD 0.58 (95% CI 0.01-1.16)] and adults, commonly seen with long-term therapy [MD 2.73 (95% CI 1.77-3.69)]. Insufficient data existed to assess most other approved ASMs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Individual ASMs may contribute to the overall metabolic and cardiovascular risk profile in patients with epilepsy. This systematic review and meta-analysis identified the need for TC and LDL monitoring in the early stages of treatment for patients taking carbamazepine or oxcarbazepine, as well as adults on phenytoin and long-term valproate therapy. Lamotrigine was associated with a reduction in LDL levels over time in adults, whereas levetiracetam had a neutral effect on the lipid profile. Furthermore, weight gain was commonly observed in both children and adults undergoing long-term treatment with valproate. Regularly ordering lipid tests could play an important role in evaluating and mitigating the ","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198494","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":"Dual Antiplatelet Therapy Versus Alteplase for Mild Stroke with Admission NIHSS Score 0-3 Versus 4-5: A Secondary Analysis of the ARAMIS Randomized Trial.","authors":"Zhao-Xia Fei, Yue Yin, Yu Cui, Thanh N Nguyen, Hui-Sheng Chen","doi":"10.1007/s40263-025-01211-6","DOIUrl":"10.1007/s40263-025-01211-6","url":null,"abstract":"<p><strong>Background: </strong>The ARAMIS trial demonstrated the non-inferiority of dual antiplatelet therapy (DAPT) to alteplase in patients with minor nondisabling ischemic stroke. We aimed to investigate whether the degree of neurological deficit can affect the benefit of DAPT versus alteplase.</p><p><strong>Methods: </strong>On the basis of the as-treated analysis set, eligible patients with acute minor nondisabling stroke were divided into NIHSS 0-3 and NIHSS 4-5 groups, which was further subdivided into DAPT and alteplase groups. The primary outcome was excellent functional outcome, defined as a mRS score of 0-1 at 90 days, and the safety outcome was symptomatic intracerebral hemorrhage (sICH).</p><p><strong>Results: </strong>A total of 719 patients were enrolled, including 585 in the NIHSS 0-3 group and 134 in the NIHSS 4-5 group. In the NIHSS score 0-3 group, the proportion of patients with mRS of 0-1 at 90 days was 95.5% (277/290) in the DAPT group and 92.2% (272/295) in the alteplase group. In the NIHSS score 4-5 group, the proportion of patients with mRS of 0 or 1 at 90 days was 82.7% (43/52) in the DAPT group and 90.2 % (74/82) in the alteplase group. A significant interaction effect was identified between the baseline NIHSS and treatment for the primary outcome (P = 0.048). There was no patient with sICH in the DAPT group. In the alteplase group, there were three and one patients with sICH in the NIHSS score 0-3 group and 4-5 group, respectively.</p><p><strong>Conclusions: </strong>Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 h of symptom onset, the benefit of DAPT versus alteplase may be affected by the degree of neurological deficit on admission. DAPT may be favored in patients with a mild neurologic deficit, while alteplase is favored in patients with a higher degree of neurologic deficit. Trial Registration ClinicalTrials.gov Identifier: NCT03661411.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1037-1046"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783586","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":"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":"913-935"},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423258/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating Changes in Clinical Outcomes after Discontinuation of Anti-CGRP Targeting Therapy for Migraine Prophylaxis: A Systematic Review and Meta-analysis.","authors":"Luana Miyahira Makita, Thales Pardini Fagundes, Pedro Henrique Reginato, Lucca Passow Carpinelli, Giovanna de Freitas Morais, Renata Trinkel Montanarin, Rafael de Freitas Kleimmann, Rafael Eduardo Streit, Aishwarya Koppanatham, Andressa Christine Sales Rodrigues, Elcio Juliato Piovesan","doi":"10.1007/s40263-025-01233-0","DOIUrl":"https://doi.org/10.1007/s40263-025-01233-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-calcitonin gene-related peptide (CGRP) therapies have significantly improved migraine prevention, but the long-term impact of discontinuation remains unclear. This systematic review and meta-analysis aimed to evaluate clinical outcomes following the cessation of anti-CGRP therapy.</p><p><strong>Methods: </strong>PubMed, Embase, and Cochrane databases were searched up to September 2024 for randomized or observational studies reporting post-discontinuation effects in patients with episodic or chronic migraine who had been preventively treated with anti-CGRP monoclonal antibodies or gepants. The primary outcome was the mean change in monthly migraine days from baseline to post-discontinuation. Secondary outcomes included acute headache medication use, the mean change in migraine frequency from active therapy to treatment cessation, and ≥ 50% responder rates. Heterogeneity was assessed with prediction intervals (PIs) for binary outcomes and I² statistics for continuous data. Random-effects models pooled mean differences (MDs) and risk ratios (RRs), with subgroup analyses based on follow-up duration, study design, and individuals with chronic migraine.</p><p><strong>Results: </strong>Eight studies (n = 1012) evaluating anti-CGRP monoclonal antibodies interruption were included. No studies on gepant cessation were found. Monthly migraine days decreased significantly post-discontinuation compared with baseline (MD -3.78; 95% CI -4.89, -2.67; I² = 57%; p < 0.05), with reductions of - 5.70 days at 1 month and - 3.62 days at 3 months. Patients with chronic migraine showed sustained reductions (MD - 6.54; 95% CI - 8.64, - 4.43; I² = 68%; p < 0.05) in the days per month with migraine between cessation and pre-treatment periods. Monthly acute headache medication days declined from baseline (MD - 1.74; 95% CI - 2.84, - 0.64; I² = 0%; p < 0.05). Monthly migraine days increased at 3 months after discontinuation compared with just before discontinuation (MD 4.43; 95% CI 2.61, 6.25; I² = 86%; p < 0.05), with monthly acute headache drug usage rising by 3.22 days. Responder rates of ≥ 50% declined (RR 0.42; 95% CI 0.33, 0.53; PI 0.17, 1.03; p < 0.05).</p><p><strong>Conclusions: </strong>Migraine burden worsened after discontinuation of anti-CGRP targeting therapies but remained lower than pretreatment levels. Further research is needed to explore disease-modifying potential and optimal discontinuation strategies. PROSPERO registration number CRD42024595771.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198526","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}