Pub Date : 2024-08-01Epub Date: 2024-05-28DOI: 10.1007/s40263-024-01096-x
Hui-Ling Qu, Xiao-Yu Sun, Chao He, Hui-Sheng Chen
Background and purpose: Sex is associated with clinical outcome in stroke. The present study aimed to determine the effect of sex on efficacy of dual antiplatelet (DAPT) versus alteplase in ischemic stroke based on Antiplatelet versus recombinant tissue plasminogen activator (R-tPA) for Acute Mild Ischemic Stroke (ARAMIS) trial.
Methods: In this secondary analysis of the ARAMIS study, eligible patients aged 18 years or older with minor nondisabling stroke who received dual antiplatelet therapy or intravenous alteplase within 4.5 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used.
Results: Of the 719 patients who completed the study, 31% (223) were women, and 69% (496) were men. There were no significant sex differences in excellent functional outcome (unadjusted p = 0.304 for men and p = 0.993 for women; adjusted p = 0.376 for men and p = 0.918 for women) and favorable functional outcome (mRS score of 0-2; unadjusted p = 0.968 for men and p = 0.881 for women; adjusted p = 0.824 for men and p = 0.881 for women). But for the secondary outcomes, compared with alteplase, DAPT was associated with a significantly decreased proportion of early neurological deterioration within 24 h in men {unadjusted odds ratio [OR] = 0.440 [95% confidence interval (CI), 0.221-0.878]; p = 0.020; adjusted OR = 0.436 [95% CI, 0.216-0.877]; p = 0.020}, but not in women [unadjusted OR = 0.636 (95% CI, 0.175-2.319), p = 0.490; adjusted OR = 0.687 (95% CI, 0.181-2.609), p = 0.581]. For the safety outcomes, compared with the DAPT group, alteplase was associated with a significantly increased proportion of any bleeding events in men [unadjusted OR = 3.110 (95% CI, 1.103-8.770); p = 0.032], but not in women [unadjusted OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; adjusted OR = 5.394 (95% CI, 0.592-49.112), p = 0.135].
Conclusion: Sex did not influence the effect of dual antiplatelet therapy versus intravenous alteplase in minor nondisabling stroke, but more early neurological deterioration and bleeding events occurred in men who received alteplase.
背景和目的:性别与中风的临床预后有关。本研究旨在根据急性轻度缺血性卒中抗血小板与重组组织纤溶酶原激活剂(R-tPA)试验(ARAMIS)确定性别对缺血性卒中双联抗血小板(DAPT)与阿替普酶疗效的影响:在这项 ARAMIS 研究的二次分析中,符合条件的 18 岁及以上非致残性轻微脑卒中患者在脑卒中发生后 4.5 小时内接受了双联抗血小板疗法或静脉注射阿替普酶后,被分为两组:男性组和女性组。主要终点是良好的功能预后,即 90 天时改良 Rankin 量表(mRS)为 0-1。研究采用了二元逻辑回归分析和广义线性模型:在完成研究的 719 名患者中,31%(223 人)为女性,69%(496 人)为男性。在优良功能预后(未经调整的男性 p = 0.304,女性 p = 0.993;调整后男性 p = 0.376,女性 p = 0.918)和良好功能预后(mRS 评分 0-2 分;未经调整的男性 p = 0.968,女性 p = 0.881;调整后男性 p = 0.824,女性 p = 0.881)方面没有明显的性别差异。但就次要结果而言,与阿替普酶相比,DAPT与男性24小时内早期神经功能恶化的比例显著降低相关{未经调整的几率比[OR] = 0.440 [95% 置信区间 (CI),0.221-0.878];p = 0.020;调整后 OR = 0.436 [95% CI,0.216-0.877];p = 0.020},但在女性中没有相关性[未调整 OR = 0.636 (95% CI,0.175-2.319),p = 0.490;调整 OR = 0.687 (95% CI,0.181-2.609),p = 0.581]。在安全性结果方面,与DAPT组相比,阿替普酶与男性[未调整OR = 3.110 (95% CI, 1.103-8.770); p = 0.032]显著增加的任何出血事件比例相关,但与女性[未调整OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; 调整OR = 5.394 (95% CI, 0.592-49.112), p = 0.135]无关:性别并不影响双联抗血小板疗法与静脉注射阿替普酶治疗轻度非致残性卒中的效果,但接受阿替普酶治疗的男性患者早期神经功能恶化和出血事件发生率更高。
{"title":"Sex Differences in the Dual Antiplatelet Therapy Versus Alteplase for Patients with Minor Nondisabling Acute Ischemic Stroke: A Secondary Analysis of the ARAMIS Study.","authors":"Hui-Ling Qu, Xiao-Yu Sun, Chao He, Hui-Sheng Chen","doi":"10.1007/s40263-024-01096-x","DOIUrl":"10.1007/s40263-024-01096-x","url":null,"abstract":"<p><strong>Background and purpose: </strong>Sex is associated with clinical outcome in stroke. The present study aimed to determine the effect of sex on efficacy of dual antiplatelet (DAPT) versus alteplase in ischemic stroke based on Antiplatelet versus recombinant tissue plasminogen activator (R-tPA) for Acute Mild Ischemic Stroke (ARAMIS) trial.</p><p><strong>Methods: </strong>In this secondary analysis of the ARAMIS study, eligible patients aged 18 years or older with minor nondisabling stroke who received dual antiplatelet therapy or intravenous alteplase within 4.5 h of stroke onset were divided into two groups: men and women. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) 0-1 at 90 days. Binary logistic regression analyses and generalized linear models were used.</p><p><strong>Results: </strong>Of the 719 patients who completed the study, 31% (223) were women, and 69% (496) were men. There were no significant sex differences in excellent functional outcome (unadjusted p = 0.304 for men and p = 0.993 for women; adjusted p = 0.376 for men and p = 0.918 for women) and favorable functional outcome (mRS score of 0-2; unadjusted p = 0.968 for men and p = 0.881 for women; adjusted p = 0.824 for men and p = 0.881 for women). But for the secondary outcomes, compared with alteplase, DAPT was associated with a significantly decreased proportion of early neurological deterioration within 24 h in men {unadjusted odds ratio [OR] = 0.440 [95% confidence interval (CI), 0.221-0.878]; p = 0.020; adjusted OR = 0.436 [95% CI, 0.216-0.877]; p = 0.020}, but not in women [unadjusted OR = 0.636 (95% CI, 0.175-2.319), p = 0.490; adjusted OR = 0.687 (95% CI, 0.181-2.609), p = 0.581]. For the safety outcomes, compared with the DAPT group, alteplase was associated with a significantly increased proportion of any bleeding events in men [unadjusted OR = 3.110 (95% CI, 1.103-8.770); p = 0.032], but not in women [unadjusted OR = 5.333 (95% CI, 0.613-46.407), p = 0.129; adjusted OR = 5.394 (95% CI, 0.592-49.112), p = 0.135].</p><p><strong>Conclusion: </strong>Sex did not influence the effect of dual antiplatelet therapy versus intravenous alteplase in minor nondisabling stroke, but more early neurological deterioration and bleeding events occurred in men who received alteplase.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"649-659"},"PeriodicalIF":7.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161441","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}
Pub Date : 2024-08-01Epub Date: 2024-06-23DOI: 10.1007/s40263-024-01099-8
Liliana Patarroyo-Rodriguez, Stefanie Cavalcanti, Jennifer L Vande Voort, Balwinder Singh
Anhedonia, a complex symptom rooted in deficits across reward processes, is primarily linked to depression and schizophrenia but transcends diagnostic boundaries across various mental disorders. Its presence correlates with poorer clinical outcomes, including an increased risk of suicide and diminished response to treatment. The neurobiological underpinnings of anhedonia remain incompletely understood despite advancements in biomarkers and imaging that contribute to deeper insights. Ketamine, known for its rapid-acting antidepressant properties, appears to possess antianhedonic effects through a mechanism of action not fully elucidated. This effect appears to be independent of its antidepressant properties. Explorations into alternative antianhedonic treatments have been underway, yet lingering questions persist, underscoring the imperative need for ongoing research to advance the field.
{"title":"The Use of Ketamine for the Treatment of Anhedonia in Depression.","authors":"Liliana Patarroyo-Rodriguez, Stefanie Cavalcanti, Jennifer L Vande Voort, Balwinder Singh","doi":"10.1007/s40263-024-01099-8","DOIUrl":"10.1007/s40263-024-01099-8","url":null,"abstract":"<p><p>Anhedonia, a complex symptom rooted in deficits across reward processes, is primarily linked to depression and schizophrenia but transcends diagnostic boundaries across various mental disorders. Its presence correlates with poorer clinical outcomes, including an increased risk of suicide and diminished response to treatment. The neurobiological underpinnings of anhedonia remain incompletely understood despite advancements in biomarkers and imaging that contribute to deeper insights. Ketamine, known for its rapid-acting antidepressant properties, appears to possess antianhedonic effects through a mechanism of action not fully elucidated. This effect appears to be independent of its antidepressant properties. Explorations into alternative antianhedonic treatments have been underway, yet lingering questions persist, underscoring the imperative need for ongoing research to advance the field.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"583-596"},"PeriodicalIF":7.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442259","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}
Pub Date : 2024-07-01Epub Date: 2024-06-05DOI: 10.1007/s40263-024-01097-w
Michael H Rosenbloom, Tricia O'Donohue, Domi Zhou-Clark, Deepashni Mala, Andrew Frazier, Michael Tarrant, Michelle Modrijan, Melora Riveira, Darla Chapman, Yvonne Griffin, Lauren Shakalis, Thomas J Grabowski
The US Food and Drug Administration (FDA) approval of lecanemab for early-stage Alzheimer's disease (AD) represents an exciting new chapter in the management of neurodegenerative disease, but likewise presents numerous clinical, technical, and financial logistical challenges for both academic and non-academic medical institutions hoping to administer this drug. Minimal resources exist that provide guidance for establishing and maintaining a lecanemab treatment program at the institutional level. The current report aims to provide healthcare institutions a framework for the planning, onboarding, and longitudinal treatment of AD with anti-amyloid monoclonal antibody treatments. We present an implementation study involving three stages: (1) feasibility assessment, (2) operations and going live, and (3) monitoring assessment. We found that implementation of lecanemab in clinical practice was feasible due to the assignment of an enterprise-wide project manager to facilitate the planning phase, a cost analysis showing that lecanemab was financially sustainable, and the development of electronic medical record tools to support operational efficiency.
{"title":"A Framework for the Administration of Anti-amyloid Monoclonal Antibody Treatments in Early-Stage Alzheimer's Disease.","authors":"Michael H Rosenbloom, Tricia O'Donohue, Domi Zhou-Clark, Deepashni Mala, Andrew Frazier, Michael Tarrant, Michelle Modrijan, Melora Riveira, Darla Chapman, Yvonne Griffin, Lauren Shakalis, Thomas J Grabowski","doi":"10.1007/s40263-024-01097-w","DOIUrl":"10.1007/s40263-024-01097-w","url":null,"abstract":"<p><p>The US Food and Drug Administration (FDA) approval of lecanemab for early-stage Alzheimer's disease (AD) represents an exciting new chapter in the management of neurodegenerative disease, but likewise presents numerous clinical, technical, and financial logistical challenges for both academic and non-academic medical institutions hoping to administer this drug. Minimal resources exist that provide guidance for establishing and maintaining a lecanemab treatment program at the institutional level. The current report aims to provide healthcare institutions a framework for the planning, onboarding, and longitudinal treatment of AD with anti-amyloid monoclonal antibody treatments. We present an implementation study involving three stages: (1) feasibility assessment, (2) operations and going live, and (3) monitoring assessment. We found that implementation of lecanemab in clinical practice was feasible due to the assignment of an enterprise-wide project manager to facilitate the planning phase, a cost analysis showing that lecanemab was financially sustainable, and the development of electronic medical record tools to support operational efficiency.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"493-505"},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247885","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}
Pub Date : 2024-07-01Epub Date: 2024-06-05DOI: 10.1007/s40263-024-01092-1
Orwa Albitar, Sabariah Noor Harun, Siti Maisharah Sheikh Ghadzi
BACKGROUND AND OBJECTIVES: Clozapine is the medication of choice for treatment-resistant schizophrenia. However, it has a complex metabolism and unexplained interindividual variability. The current work aims to develop a pharmacokinetic model of clozapine and norclozapine in non-smokers and assess the impact of demographic and genetic predictors.
Methods: Healthy volunteers were recruited in a population pharmacokinetic study. Blood samples were collected at 30 min and 1, 2, 3, 5 and 8 h following a single flat dose of clozapine (12.5 mg). The clozapine and norclozapine concentrations were measured via high-performance liquid chromatography-ultraviolet method. A semi-physiological pharmacokinetic model of clozapine and norclozapine was developed using nonlinear mixed-effects modeling. Clinical and genetic predictors were evaluated, including CYP1A2 (rs762551) and ABCB1 (rs2032582), using restriction fragment length polymorphism.
Results: A total of 270 samples were collected from 33 participants. The data were best described using a two-compartment model for clozapine and a two-compartment model for norclozapine with first-order absorption and elimination and pre-systemic metabolism. The estimated (relative standard error) clearance of clozapine and norclozapine were 27 L h-1 (31.5 %) and 19.6 L h-1 (30%), respectively. Clozapine clearance was lower in sub-Saharan Africans (n = 4) and higher in Caucasians (n = 9) than Asians (n = 20). Participants with CYP1A2 (rs762551) (n = 18) and ABCB1 (rs2032582) (n = 12) mutant alleles had lower clozapine clearance in the univariate analysis.
Conclusions: This is the first study to develop a semi-physiological pharmacokinetic model of clozapine and norclozapine accounting for the pre-systemic metabolism. Asians required lower doses of clozapine as compared with Caucasians, while clozapine pharmacokinetics in sub-Saharan Africans should be further investigated in larger trials.
{"title":"Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.","authors":"Orwa Albitar, Sabariah Noor Harun, Siti Maisharah Sheikh Ghadzi","doi":"10.1007/s40263-024-01092-1","DOIUrl":"10.1007/s40263-024-01092-1","url":null,"abstract":"<p><p>BACKGROUND AND OBJECTIVES: Clozapine is the medication of choice for treatment-resistant schizophrenia. However, it has a complex metabolism and unexplained interindividual variability. The current work aims to develop a pharmacokinetic model of clozapine and norclozapine in non-smokers and assess the impact of demographic and genetic predictors.</p><p><strong>Methods: </strong>Healthy volunteers were recruited in a population pharmacokinetic study. Blood samples were collected at 30 min and 1, 2, 3, 5 and 8 h following a single flat dose of clozapine (12.5 mg). The clozapine and norclozapine concentrations were measured via high-performance liquid chromatography-ultraviolet method. A semi-physiological pharmacokinetic model of clozapine and norclozapine was developed using nonlinear mixed-effects modeling. Clinical and genetic predictors were evaluated, including CYP1A2 (rs762551) and ABCB1 (rs2032582), using restriction fragment length polymorphism.</p><p><strong>Results: </strong>A total of 270 samples were collected from 33 participants. The data were best described using a two-compartment model for clozapine and a two-compartment model for norclozapine with first-order absorption and elimination and pre-systemic metabolism. The estimated (relative standard error) clearance of clozapine and norclozapine were 27 L h<sup>-1</sup> (31.5 %) and 19.6 L h<sup>-1</sup> (30%), respectively. Clozapine clearance was lower in sub-Saharan Africans (n = 4) and higher in Caucasians (n = 9) than Asians (n = 20). Participants with CYP1A2 (rs762551) (n = 18) and ABCB1 (rs2032582) (n = 12) mutant alleles had lower clozapine clearance in the univariate analysis.</p><p><strong>Conclusions: </strong>This is the first study to develop a semi-physiological pharmacokinetic model of clozapine and norclozapine accounting for the pre-systemic metabolism. Asians required lower doses of clozapine as compared with Caucasians, while clozapine pharmacokinetics in sub-Saharan Africans should be further investigated in larger trials.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"571-581"},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247951","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}
Pub Date : 2024-07-01Epub Date: 2024-05-31DOI: 10.1007/s40263-024-01091-2
Nazia Karsan, Peter J Goadsby
Migraine is a common brain condition characterised by disabling attacks of headache with sensory sensitivities. Despite increasing understanding of migraine neurobiology and the impacts of this on therapeutic developments, there remains a need for treatment options for patients underserved by currently available therapies. The first specific drugs developed to treat migraine acutely, the serotonin-5-hydroxytryptamine [5-HT1B/1D] receptor agonists (triptans), seem to require headache onset in order to have an effect, while early treatment during mild pain before headache escalation improves short-term and long-term outcomes. Some patients find treating in the early window once headache has started but not escalated difficult, and migraine can arise from sleep or in the early hours of the morning, making prompt treatment after pain onset challenging. Triptans may be deemed unsuitable for use in patients with vascular disease and in those of older age and may not be effective in a proportion of patients. Headache is also increasingly recognised as being just one of the many facets of the migraine attack, and for some patients it is not the most disabling symptom. In many patients, painless symptoms can start prior to headache onset and can reliably warn of impending headache. There is, therefore, a need to identify therapeutic targets and agents that may be used as early as possible in the course of the attack, to prevent headache onset before it starts, and to reduce both headache and non-headache related attack burden. Early small studies using domperidone, naratriptan and dihydroergotamine have suggested that this approach could be useful; these studies were methodologically less rigorous than modern day treatment studies, of small sample size, and have not since been replicated. The emergence of novel targeted migraine treatments more recently, specifically calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), has reignited interest in this strategy, with encouraging results. This review summarises historical and emerging data in this area, supporting use of the premonitory phase as an opportunity to intervene as early as possible in migraine to prevent attack-related morbidity.
{"title":"Intervening in the Premonitory Phase to Prevent Migraine: Prospects for Pharmacotherapy.","authors":"Nazia Karsan, Peter J Goadsby","doi":"10.1007/s40263-024-01091-2","DOIUrl":"10.1007/s40263-024-01091-2","url":null,"abstract":"<p><p>Migraine is a common brain condition characterised by disabling attacks of headache with sensory sensitivities. Despite increasing understanding of migraine neurobiology and the impacts of this on therapeutic developments, there remains a need for treatment options for patients underserved by currently available therapies. The first specific drugs developed to treat migraine acutely, the serotonin-5-hydroxytryptamine [5-HT<sub>1B/1D</sub>] receptor agonists (triptans), seem to require headache onset in order to have an effect, while early treatment during mild pain before headache escalation improves short-term and long-term outcomes. Some patients find treating in the early window once headache has started but not escalated difficult, and migraine can arise from sleep or in the early hours of the morning, making prompt treatment after pain onset challenging. Triptans may be deemed unsuitable for use in patients with vascular disease and in those of older age and may not be effective in a proportion of patients. Headache is also increasingly recognised as being just one of the many facets of the migraine attack, and for some patients it is not the most disabling symptom. In many patients, painless symptoms can start prior to headache onset and can reliably warn of impending headache. There is, therefore, a need to identify therapeutic targets and agents that may be used as early as possible in the course of the attack, to prevent headache onset before it starts, and to reduce both headache and non-headache related attack burden. Early small studies using domperidone, naratriptan and dihydroergotamine have suggested that this approach could be useful; these studies were methodologically less rigorous than modern day treatment studies, of small sample size, and have not since been replicated. The emergence of novel targeted migraine treatments more recently, specifically calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), has reignited interest in this strategy, with encouraging results. This review summarises historical and emerging data in this area, supporting use of the premonitory phase as an opportunity to intervene as early as possible in migraine to prevent attack-related morbidity.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"533-546"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183872","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}
Pub Date : 2024-07-01Epub Date: 2024-05-07DOI: 10.1007/s40263-024-01089-w
Megan Galbally, Karen Wynter, Dan Siskind, Christoph U Correll, Korinne Northwood, Susanna Every-Palmer
Background and objective: Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability.
Methods: This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters.
Results: There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reported weight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or other laboratory indicators were found.
Conclusions: While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia.
{"title":"Sex Differences Between Female and Male Individuals in Antipsychotic Efficacy and Adverse Effects in the Treatment of Schizophrenia.","authors":"Megan Galbally, Karen Wynter, Dan Siskind, Christoph U Correll, Korinne Northwood, Susanna Every-Palmer","doi":"10.1007/s40263-024-01089-w","DOIUrl":"10.1007/s40263-024-01089-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability.</p><p><strong>Methods: </strong>This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters.</p><p><strong>Results: </strong>There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reported weight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or other laboratory indicators were found.</p><p><strong>Conclusions: </strong>While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"559-570"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852893","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}
Pub Date : 2024-07-01Epub Date: 2024-06-03DOI: 10.1007/s40263-024-01093-0
Adrián Gucký, Slávka Hamuľaková
Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.
人体的许多生理过程,包括大脑的发育和功能,都需要铁、铜和锌等生物金属离子的参与。然而,它们的失衡可能会导致阿尔茨海默病(AD)和其他潜在的神经退行性疾病的发生。因此,螯合生物金属离子是一种针对阿尔茨海默病的治疗策略。本综述对目前或可能用于针对 AD 金属假说的天然和合成螯合剂进行了调查。由于金属失衡并不是 AD 的唯一病理方面,而且这种疾病的性质非常复杂,具有多因素性,因此最有效的治疗方法应尽可能多地针对神经毒性因素。各种香豆素衍生物符合这一描述,除了能够螯合金属离子外,它们还具有抑制胆碱酯酶(ChEs)和单胺氧化酶 B(MAO-B)的能力,同时还具有抗氧化、抗炎和许多其他有益作用。因此,基于香豆素支架的化合物是一类理想的抗逆转录酶治疗药物。
{"title":"Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.","authors":"Adrián Gucký, Slávka Hamuľaková","doi":"10.1007/s40263-024-01093-0","DOIUrl":"10.1007/s40263-024-01093-0","url":null,"abstract":"<p><p>Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"507-532"},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199629","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}
Pub Date : 2024-06-01Epub Date: 2024-05-09DOI: 10.1007/s40263-024-01090-3
Nouf Alfaidi, Salama Karmastaji, Alexandria Matic, Vera Bril
In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies are engineered to selectively target FcRn through various methods, such as Fc fragments or monoclonal anti-FcRn antibodies. These approaches enhance the breakdown of autoantibodies by blocking the immunoglobulin G recycling pathway. This mechanism reduces overall plasma immunoglobulin levels, including the levels of pathogenic autoantibodies, without affecting the other immunoglobulin class immunoglobulin A, immunoglobulin E, immunoglobulin M, and immunoglobulin D levels. Drugs that inhibit FcRn include efgartigimod, rozanolixizumab, batoclimab, and nipocalimab. These medications can be administered either intravenously or subcutaneously. Numerous clinical trials are currently underway to investigate their effectiveness, safety, and tolerability in various neurological conditions, including myasthenia gravis and other neurological disorders such as chronic inflammatory demyelinating polyneuropathy, myositis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. Positive results from clinical trials of efgartigimod and rozanolixizumab led to their approval for the treatment of generalized myasthenia gravis. Additional clinical trials are still ongoing. Neonatal Fc receptor inhibitor agents seem to be well tolerated. Reported adverse events include headache (most commonly observed with efgartigimod and rozanolixizumab), upper respiratory tract infection, urinary tract infection, diarrhea, pyrexia, and nausea. Additionally, some of these agents may cause transient hypoalbuminemia and hypercholesterolemia notably reported with batoclimab and nipocalimab. In this review, we discuss the available clinical data for FcRN inhibitor agents in treating different neurological autoimmune diseases.
近十年来,随着新型靶向疗法的出现和获批,治疗自身免疫性疾病的格局发生了变化。一些新型生物制剂提供了选择性和靶向特异性免疫疗法,因此副作用较少,例如新生儿 Fc 受体(FcRn)靶向疗法。新生儿 Fc 受体靶向疗法通过各种方法,如 Fc 片段或单克隆抗 FcRn 抗体,选择性地靶向 FcRn。这些方法通过阻断免疫球蛋白 G 的循环途径来加强自身抗体的分解。这种机制可降低血浆免疫球蛋白的总体水平,包括致病性自身抗体的水平,而不会影响其他免疫球蛋白类免疫球蛋白 A、免疫球蛋白 E、免疫球蛋白 M 和免疫球蛋白 D 的水平。抑制 FcRn 的药物包括依加替莫德(efgartigimod)、罗扎尼珠单抗(rozanolixizumab)、巴妥珠单抗(batoclimab)和尼泊卡单抗(nipocalimab)。这些药物可以静脉注射或皮下注射。目前正在进行大量临床试验,以研究这些药物对各种神经系统疾病的有效性、安全性和耐受性,包括重症肌无力和其他神经系统疾病,如慢性炎症性脱髓鞘性多发性神经病、肌炎、神经性视脊髓炎和髓鞘少突胶质细胞糖蛋白抗体病。依加替莫德(efgartigimod)和罗扎尼珠单抗(rozanolixizumab)的临床试验结果良好,因此被批准用于治疗全身性重症肌无力。其他临床试验仍在进行中。新生儿 Fc 受体抑制剂似乎耐受性良好。已报告的不良反应包括头痛(最常见于依加替莫德和罗扎尼单抗)、上呼吸道感染、泌尿道感染、腹泻、发热和恶心。此外,这些药物中的一些可能会导致一过性低白蛋白血症和高胆固醇血症,巴妥珠单抗和尼泊卡珠单抗的报道尤为明显。在本综述中,我们将讨论 FcRN 抑制剂治疗不同神经系统自身免疫性疾病的现有临床数据。
{"title":"FcRn Inhibitor Therapies in Neurologic Diseases.","authors":"Nouf Alfaidi, Salama Karmastaji, Alexandria Matic, Vera Bril","doi":"10.1007/s40263-024-01090-3","DOIUrl":"10.1007/s40263-024-01090-3","url":null,"abstract":"<p><p>In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies are engineered to selectively target FcRn through various methods, such as Fc fragments or monoclonal anti-FcRn antibodies. These approaches enhance the breakdown of autoantibodies by blocking the immunoglobulin G recycling pathway. This mechanism reduces overall plasma immunoglobulin levels, including the levels of pathogenic autoantibodies, without affecting the other immunoglobulin class immunoglobulin A, immunoglobulin E, immunoglobulin M, and immunoglobulin D levels. Drugs that inhibit FcRn include efgartigimod, rozanolixizumab, batoclimab, and nipocalimab. These medications can be administered either intravenously or subcutaneously. Numerous clinical trials are currently underway to investigate their effectiveness, safety, and tolerability in various neurological conditions, including myasthenia gravis and other neurological disorders such as chronic inflammatory demyelinating polyneuropathy, myositis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. Positive results from clinical trials of efgartigimod and rozanolixizumab led to their approval for the treatment of generalized myasthenia gravis. Additional clinical trials are still ongoing. Neonatal Fc receptor inhibitor agents seem to be well tolerated. Reported adverse events include headache (most commonly observed with efgartigimod and rozanolixizumab), upper respiratory tract infection, urinary tract infection, diarrhea, pyrexia, and nausea. Additionally, some of these agents may cause transient hypoalbuminemia and hypercholesterolemia notably reported with batoclimab and nipocalimab. In this review, we discuss the available clinical data for FcRN inhibitor agents in treating different neurological autoimmune diseases.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"425-441"},"PeriodicalIF":6.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897610","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}
Pub Date : 2024-05-01Epub Date: 2024-03-23DOI: 10.1007/s40263-024-01077-0
Rachel Goldstein, Natalie Rabkin, Noa Buchman, Aviya R Jacobs, Khaled Sandouka, Bruria Raccah, Tamar Fisher Negev, Ilan Matok, Meir Bialer, Mordechai Muszkat
Background and objective: Post-stroke epilepsy represents an important clinical challenge as it often requires both treatment with direct oral anticoagulants (DOACs) and antiseizure medications (ASMs). Levetiracetam (LEV), an ASM not known to induce metabolizing enzymes, has been suggested as a safer alternative to enzyme-inducing (EI)-ASMs in patients treated with DOACs; however, current clinical guidelines suggest caution when LEV is used with DOACs because of possible P-glycoprotein induction and competition (based on preclinical studies). We investigated whether LEV affects apixaban and rivaroxaban concentrations compared with two control groups: (a) patients treated with EI-ASMs and (b) patients not treated with any ASM.
Methods: In this retrospective observational study, we monitored apixaban and rivaroxaban peak plasma concentrations (Cmax) in 203 patients treated with LEV (n = 28) and with EI-ASM (n = 33), and in patients not treated with any ASM (n = 142). Enzyme-inducing ASMs included carbamazepine, phenytoin, phenobarbital, primidone, and oxcarbazepine. We collected clinical and laboratory data for analysis, and DOAC Cmax of patients taking LEV were compared with the other two groups.
Results: In 203 patients, 55% were female and the mean age was 78 ± 0.8 years. One hundred and eighty-six patients received apixaban and 17 patients received rivaroxaban. The proportion of patients with DOAC Cmax below their therapeutic range was 7.1% in the LEV group, 10.6% in the non-ASM group, and 36.4% in the EI-ASM group (p < 0.001). The odds of having DOAC Cmax below the therapeutic range (compared with control groups) was not significantly different in patients taking LEV (adjusted odds ratio 0.70, 95% confidence interval 0.19-2.67, p = 0.61), but it was 12.7-fold higher in patients taking EI-ASM (p < 0.001). In an analysis in patients treated with apixaban, there was no difference in apixaban Cmax between patients treated with LEV and non-ASM controls, and LEV clinical use was not associated with variability in apixaban Cmax in a multivariate linear regression.
Conclusions: In this study, we show that unlike EI-ASMs, LEV clinical use was not significantly associated with lower apixaban Cmax and was similar to that in patients not treated with any ASM. Our findings suggest that the combination of LEV with apixaban and rivaroxaban may not be associated with decreased apixaban and rivaroxaban Cmax. Therefore, prospective controlled studies are required to examine the possible non-pharmacokinetic mechanism of the effect of the LEV-apixaban or LEV-rivaroxaban combination on patients' outcomes.
{"title":"The Effect of Levetiracetam Compared with Enzyme-Inducing Antiseizure Medications on Apixaban and Rivaroxaban Peak Plasma Concentrations.","authors":"Rachel Goldstein, Natalie Rabkin, Noa Buchman, Aviya R Jacobs, Khaled Sandouka, Bruria Raccah, Tamar Fisher Negev, Ilan Matok, Meir Bialer, Mordechai Muszkat","doi":"10.1007/s40263-024-01077-0","DOIUrl":"10.1007/s40263-024-01077-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Post-stroke epilepsy represents an important clinical challenge as it often requires both treatment with direct oral anticoagulants (DOACs) and antiseizure medications (ASMs). Levetiracetam (LEV), an ASM not known to induce metabolizing enzymes, has been suggested as a safer alternative to enzyme-inducing (EI)-ASMs in patients treated with DOACs; however, current clinical guidelines suggest caution when LEV is used with DOACs because of possible P-glycoprotein induction and competition (based on preclinical studies). We investigated whether LEV affects apixaban and rivaroxaban concentrations compared with two control groups: (a) patients treated with EI-ASMs and (b) patients not treated with any ASM.</p><p><strong>Methods: </strong>In this retrospective observational study, we monitored apixaban and rivaroxaban peak plasma concentrations (C<sub>max</sub>) in 203 patients treated with LEV (n = 28) and with EI-ASM (n = 33), and in patients not treated with any ASM (n = 142). Enzyme-inducing ASMs included carbamazepine, phenytoin, phenobarbital, primidone, and oxcarbazepine. We collected clinical and laboratory data for analysis, and DOAC C<sub>max</sub> of patients taking LEV were compared with the other two groups.</p><p><strong>Results: </strong>In 203 patients, 55% were female and the mean age was 78 ± 0.8 years. One hundred and eighty-six patients received apixaban and 17 patients received rivaroxaban. The proportion of patients with DOAC C<sub>max</sub> below their therapeutic range was 7.1% in the LEV group, 10.6% in the non-ASM group, and 36.4% in the EI-ASM group (p < 0.001). The odds of having DOAC C<sub>max</sub> below the therapeutic range (compared with control groups) was not significantly different in patients taking LEV (adjusted odds ratio 0.70, 95% confidence interval 0.19-2.67, p = 0.61), but it was 12.7-fold higher in patients taking EI-ASM (p < 0.001). In an analysis in patients treated with apixaban, there was no difference in apixaban C<sub>max</sub> between patients treated with LEV and non-ASM controls, and LEV clinical use was not associated with variability in apixaban C<sub>max</sub> in a multivariate linear regression.</p><p><strong>Conclusions: </strong>In this study, we show that unlike EI-ASMs, LEV clinical use was not significantly associated with lower apixaban C<sub>max</sub> and was similar to that in patients not treated with any ASM. Our findings suggest that the combination of LEV with apixaban and rivaroxaban may not be associated with decreased apixaban and rivaroxaban C<sub>max</sub>. Therefore, prospective controlled studies are required to examine the possible non-pharmacokinetic mechanism of the effect of the LEV-apixaban or LEV-rivaroxaban combination on patients' outcomes.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"399-408"},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11026229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193519","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}
Pub Date : 2024-04-30DOI: 10.1007/s40263-024-01088-x
Loretta Giuliano, Vania Durante, Giulia Battaglia, Sara Gasparini, Elena Zambrelli, Caterina Ermio, Angela La Neve, Barbara Mostacci
Background
Sex differences in epilepsy have been described in prevalence, seizure propensity and response to treatment. Therefore, taking into account sex-based differences in epilepsy is important for both diagnostic purposes and therapeutic considerations. However, little is known about sex differences in adverse effects of antiseizure medications (ASMs).
Objectives
We performed a systematic review searching for sex differences in adverse effects of ASMs in adult persons with epilepsy (PWE) as part of a wider project aimed to assess sex-based differences in efficacy and adverse effects of ASMs in PWE.
Methods
We conducted a comprehensive literature search in the PubMed database. The search was conducted with no restriction on publication date, and all results up to April 2020 were included. We included articles written in English, Italian, Spanish, or French that evaluated adverse effects of one or more ASMs in PWE, with specific mention of the two sexes. When appropriate, Newcastle-Ottawa or Jadad scales were used to assess study quality.
Results
Of 5164 identified studies, only 167 considered sex in the analysis and were therefore included. Significant sex-related differences were found in 58 of those studies. We found a consistently higher frequency of cutaneous adverse effects in females; higher risk of developing general adverse effects on different ASMs in females; stronger risk of adverse effects on bone metabolism in females, mainly on treatment with enzyme-inducing ASMs; a concordant higher risk of visual field loss was noted in males on vigabatrin; an overall worse lipid profile in males; as well as higher leptin levels and higher body mass index in females treated with various ASMs.
Conclusions
Our analysis has identified some important sex differences in the adverse effects of ASMs. Clinicians should be aware of these differences when informing patients about the risks associated with ASM treatment in PWE.
{"title":"Sex Differences in Adverse Effects of Antiseizure Medications in Adults with Epilepsy: A Systematic Review","authors":"Loretta Giuliano, Vania Durante, Giulia Battaglia, Sara Gasparini, Elena Zambrelli, Caterina Ermio, Angela La Neve, Barbara Mostacci","doi":"10.1007/s40263-024-01088-x","DOIUrl":"https://doi.org/10.1007/s40263-024-01088-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Sex differences in epilepsy have been described in prevalence, seizure propensity and response to treatment. Therefore, taking into account sex-based differences in epilepsy is important for both diagnostic purposes and therapeutic considerations. However, little is known about sex differences in adverse effects of antiseizure medications (ASMs).</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We performed a systematic review searching for sex differences in adverse effects of ASMs in adult persons with epilepsy (PWE) as part of a wider project aimed to assess sex-based differences in efficacy and adverse effects of ASMs in PWE.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a comprehensive literature search in the PubMed database. The search was conducted with no restriction on publication date, and all results up to April 2020 were included. We included articles written in English, Italian, Spanish, or French that evaluated adverse effects of one or more ASMs in PWE, with specific mention of the two sexes. When appropriate, Newcastle-Ottawa or Jadad scales were used to assess study quality.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of 5164 identified studies, only 167 considered sex in the analysis and were therefore included. Significant sex-related differences were found in 58 of those studies. We found a consistently higher frequency of cutaneous adverse effects in females; higher risk of developing general adverse effects on different ASMs in females; stronger risk of adverse effects on bone metabolism in females, mainly on treatment with enzyme-inducing ASMs; a concordant higher risk of visual field loss was noted in males on vigabatrin; an overall worse lipid profile in males; as well as higher leptin levels and higher body mass index in females treated with various ASMs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Our analysis has identified some important sex differences in the adverse effects of ASMs. Clinicians should be aware of these differences when informing patients about the risks associated with ASM treatment in PWE.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"25 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829367","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}