Alzheimer's disease (AD) is a leading cause of mortality worldwide. One of the newer treatments for AD is amyloid beta (Aβ) directed monoclonal antibodies (mAbs). This systematic review and meta-analysis aimed to assess the efficacy and safety of this class of drugs.
Methods
A comprehensive literature search was conducted across Scopus, Web of Science, PubMed, and the Cochrane Library until January 30, 2025, focusing on phase III randomized controlled trials (RCTs) evaluating anti-Aβ mAbs.
Results
Twelve RCTs with 24 arms were included. Anti-Aβ mAbs significantly reduced the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score (mean difference (MD): −0.16, 95% confidence interval (CI) (−0.29, −0.04)), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score (MD: −0.87, 95% CI (−1.13, −0.60)), and amyloid positron emission tomography (PET) standardized uptake value ratio (SUVR) (MD: −0.11, 95% CI (−0.19, −0.02)). They also significantly increased the Mini-Mental State Examination (MMSE) score (MD: 0.31, 95% CI (0.15, 0.46)) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score (MD: 1.21, 95% CI (0.89, 1.53)). However, they were associated with a significant increase in complications, including amyloid-related imaging abnormalities-edema/effusion (ARIA-E) (odds ratio (OR): 10.20, 95% CI (7.17, 14.50)), ARIA-hemosiderosis or microhemorrhage (ARIA-H) (OR: 1.75, 95% CI (1.22, 2.50)), and any adverse events (OR: 1.22, 95% CI (1.08, 1.38), I2: 48.59%)). The subgroup analysis showed that treatment administered in the early/preclinical stages of AD resulted in a greater reduction in CDR-SB and ADAS-Cog scores, as well as in amyloid burden.
Conclusions
Anti-Aβ mAbs offer modest clinical benefits, and pose some serious complications, necessitating a cautious approach to their prescription.
{"title":"The Efficacy and Safety of Amyloid Beta-Directed Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Phase III Randomized Controlled Trials","authors":"Yun Wei, Hualing Li","doi":"10.1002/hup.70017","DOIUrl":"https://doi.org/10.1002/hup.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a leading cause of mortality worldwide. One of the newer treatments for AD is amyloid beta (Aβ) directed monoclonal antibodies (mAbs). This systematic review and meta-analysis aimed to assess the efficacy and safety of this class of drugs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted across Scopus, Web of Science, PubMed, and the Cochrane Library until January 30, 2025, focusing on phase III randomized controlled trials (RCTs) evaluating anti-Aβ mAbs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve RCTs with 24 arms were included. Anti-Aβ mAbs significantly reduced the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score (mean difference (MD): −0.16, 95% confidence interval (CI) (−0.29, −0.04)), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score (MD: −0.87, 95% CI (−1.13, −0.60)), and amyloid positron emission tomography (PET) standardized uptake value ratio (SUVR) (MD: −0.11, 95% CI (−0.19, −0.02)). They also significantly increased the Mini-Mental State Examination (MMSE) score (MD: 0.31, 95% CI (0.15, 0.46)) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score (MD: 1.21, 95% CI (0.89, 1.53)). However, they were associated with a significant increase in complications, including amyloid-related imaging abnormalities-edema/effusion (ARIA-E) (odds ratio (OR): 10.20, 95% CI (7.17, 14.50)), ARIA-hemosiderosis or microhemorrhage (ARIA-H) (OR: 1.75, 95% CI (1.22, 2.50)), and any adverse events (OR: 1.22, 95% CI (1.08, 1.38), I<sup>2</sup>: 48.59%)). The subgroup analysis showed that treatment administered in the early/preclinical stages of AD resulted in a greater reduction in CDR-SB and ADAS-Cog scores, as well as in amyloid burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Anti-Aβ mAbs offer modest clinical benefits, and pose some serious complications, necessitating a cautious approach to their prescription.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renée Martin-Willett, Carillon J. Skrzynski, Angela D. Bryan, L. Cinnamon Bidwell
Objective
This study examined the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) on negative mood and drinking behaviors, and whether those effects were moderated by levels of perceived discrimination among participants who identify with a racial, ethnic, gender, or sexual identity that is underrepresented in research.
Methods
Participants were either not using cannabis, using cannabis with THC, or using cannabis with CBD and were assessed at baseline, 2 weeks, and 4-weeks following ad libitum use of a legal market cannabis product that was randomly assigned to them. Primary outcomes included scores on the Depression Anxiety Stress (DASS) Scale and number of drinking days. Moderation analyses used the Perceived Discrimination Scale (PDS).
Results
172 participants who were 62% female and mean age = 30.2 were included (not using cannabis = 20, using cannabis = 152; of those, THC = 96, CBD = 56). There were significant changes in DASS scores over time, with participants using CBD experiencing greater decreases in symptoms versus participants using THC. There was also a marginal conditionXtimeXPDS interaction that was significant when the condition not using cannabis was removed from the analysis. In this case, participants in the CBD and THC conditions shared a general linear trend of decreasing DASS total scores over time, but only at average (mean) and high (+1 SD) levels of PDS scores. There were no significant effects on alcohol-related outcomes.
Conclusions
CBD may be helpful in reducing negative emotional symptoms in the short term without increasing risk for disordered alcohol use, and perceived discrimination plays a significant role in this relationship.
Trial Registration
Clinicaltrials. gov (NCT03491384; Registration Date 2018-02-28); Open Science Framework
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Mike Stedman, Mark Davies, John Warner- Levy, Joseph Ingram, David Taylor, Adrian Heald
Introduction
We describe prescribing of anxiolytics/hypnotics/antidepressants at an all-England level between 2010 and 2023, taking account of the influence of the COVID-19 pandemic-period.
Methods
All Primary Care Prescribing data for England for anxiolytics/hypnotics/antidepressant agents taken as tablets or capsules from 1 January 2010 to 31 December 2023 were considered.
Results
Antidepressants: the greatest increases were in sertraline prescriptions increasing from 2.9million 2010 by 685% to 23.0 million-2023; duloxetine increased by 545% to 3.9million prescriptions; mirtazapine by 269% to 12.4million prescriptions. Regarding cost, overall average cost fell 2010-2023 by 54% from £4.86(Euros 5.68) to £2.25(Euros 2.63) per prescription. Anxiolytics: the number of prescriptions for anxiolytics fell 6.5–4.8 m (−27%) overall, with all anxiolytics falling except buspirone. The greatest period of fall was seen between 2018 and 2023. Lorazepam/diazepam/chlordiazepoxide were down 23%,16%, 88% respectively. Average cost of prescriptions fell by 13% to £3.20(Euros 3.74). Hypnotics: the number of prescriptions for hypnotics fell 41% from 9.8million to 5.8million in 2023. All prescriptions fell in number. Annual trends showed no deviations for the COVID-19 core pandemic (2020/2021) years.
Conclusion
Overall trends demonstrate a more than doubling of antidepressant prescribing over the period 2010–2023, with similar volume reduction in anxiolytics/hypnotics over the same period. Such real world data facilitate the development of policy influencing insights for psychotropic prescribing management now and in coming years.
{"title":"National Prescribing Trends and Cost Analysis of Antidepressants, Anxiolytics, and Hypnotics in England, 2010–2023","authors":"Mike Stedman, Mark Davies, John Warner- Levy, Joseph Ingram, David Taylor, Adrian Heald","doi":"10.1002/hup.70011","DOIUrl":"https://doi.org/10.1002/hup.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>We describe prescribing of anxiolytics/hypnotics/antidepressants at an all-England level between 2010 and 2023, taking account of the influence of the COVID-19 pandemic-period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All Primary Care Prescribing data for England for anxiolytics/hypnotics/antidepressant agents taken as tablets or capsules from 1 January 2010 to 31 December 2023 were considered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Antidepressants: the greatest increases were in sertraline prescriptions increasing from 2.9million 2010 by 685% to 23.0 million-2023; duloxetine increased by 545% to 3.9million prescriptions; mirtazapine by 269% to 12.4million prescriptions. Regarding cost, overall average cost fell 2010-2023 by 54% from £4.86(Euros 5.68) to £2.25(Euros 2.63) per prescription. Anxiolytics: the number of prescriptions for anxiolytics fell 6.5–4.8 m (−27%) overall, with all anxiolytics falling except buspirone. The greatest period of fall was seen between 2018 and 2023. Lorazepam/diazepam/chlordiazepoxide were down 23%,16%, 88% respectively. Average cost of prescriptions fell by 13% to £3.20(Euros 3.74). Hypnotics: the number of prescriptions for hypnotics fell 41% from 9.8million to 5.8million in 2023. All prescriptions fell in number. Annual trends showed no deviations for the COVID-19 core pandemic (2020/2021) years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall trends demonstrate a more than doubling of antidepressant prescribing over the period 2010–2023, with similar volume reduction in anxiolytics/hypnotics over the same period. Such real world data facilitate the development of policy influencing insights for psychotropic prescribing management now and in coming years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The metaphorical expression ‘Don't mistake the signpost for the destination’ cautions against the dual pitfalls of becoming over-preoccupied with the details of a route and of being prematurely encouraged by interim way-posts, when undertaking an adventurous journey towards a cherished goal. In psychiatric practice, patients with mental health problems and their attending professionals from varying disciplines still yearn for the targeted discovery and routine implementation of individually tailored approaches, designed to shorten the course of illness and improve other clinical outcomes. This personalised medicine approach, which underpins the ‘precision psychiatry’ movement (Fernandes et al. 2017), has the laudable ambition of ‘getting the right treatment to the right patient at the right time’, and has gained additional momentum through the recent publication of the Precision Psychiatry Roadmap (PPR) (Kas et al. 2025), constructed by a consortium including patient organisations, clinicians, scientists, industrial representatives and regulatory agencies. Its carefully crafted eight sub-components, five phases (envisaged to occur over at least 15 years) and 10 anticipated future implementation steps together provide a detailed plan, for incorporating biology-informed evidence into symptom-based diagnoses so allowing for the discovery, development and deployment of mechanism-based treatments for patients with mental disorders, designed to be more effective and acceptable than current approaches. So, how useful might such a ‘map’ be?
It is worth considering two fundamental challenges. First, idioms of psychological distress vary between individuals and across cultures, patients offer psychological complaints to clinicians in variable ways, and health professionals differ in their preferred style in asking direct questions about key symptoms necessary for accurate psychiatric diagnosis. For example, even within a single country, there is worrying variation between mental health services in the comprehensiveness of patient assessment in anxiety and depressive disorders, leading to concerns about the validity and reliability of recorded psychiatric diagnosis (Baldwin et al. 2021). In addition, reporting of psychological symptoms is affected by illness-related difficulties in recollection and processing of emotional information (Jongs et al. 2022). It seems probable that ‘biology-informed evidence’ could only help to supplement and refine treatment decisions based on symptom-based diagnoses when symptoms are sought and evaluated in a standardised but culturally sensitive manner, through structured clinical interviews and robust psychometric rating scales. Second, whilst the PPR authors rightly acknowledge the importance of evaluating the individual ‘exposome’—which incorporates detailed consideration of personal factors such as socioeconomic status, lived environment, trauma exposure,
“不要把路标误认为目的地”这句比喻性的表达告诫人们，当你开始一段冒险之旅，朝着一个珍视的目标前进时，不要过度关注路线的细节，也不要过早地受到临时路标的鼓励，以免陷入双重陷阱。在精神病学实践中，患有精神健康问题的患者及其来自不同学科的主治医生仍然渴望有针对性地发现和常规实施个性化定制的方法，旨在缩短病程并改善其他临床结果。这种个性化医疗方法是“精准精神病学”运动的基础（Fernandes et al. 2017），其“在正确的时间为正确的患者提供正确的治疗”的雄心值得称赞，并通过最近出版的精准精神病学路线图（PPR） （Kas et al. 2025）获得了额外的动力，该路线图由包括患者组织，临床医生，科学家，工业代表和监管机构在内的联盟构建。其精心设计的八个子部分，五个阶段（预计至少在15年内完成）和10个预期的未来实施步骤共同提供了一个详细的计划，将生物学证据纳入基于症状的诊断，从而允许发现、开发和部署基于机制的精神障碍患者治疗方法，旨在比目前的方法更有效和更可接受。那么，这样的“地图”有多大用处呢？有两个基本挑战值得考虑。首先，心理困扰的习语因个人和文化而异，患者以不同的方式向临床医生提供心理抱怨，卫生专业人员在询问准确的精神病诊断所必需的关键症状时，他们喜欢的直接问题方式也不同。例如，即使在一个国家内，精神卫生服务机构在对焦虑症和抑郁症患者评估的全面性方面也存在令人担忧的差异，导致人们对记录的精神病诊断的有效性和可靠性感到担忧（Baldwin et al. 2021）。此外，心理症状的报告还受到与疾病有关的回忆和情绪信息处理困难的影响（Jongs et al. 2022）。通过结构化的临床访谈和健全的心理测量量表，以标准化但具有文化敏感性的方式寻求和评估症状时，“生物学证据”似乎只能帮助补充和完善基于症状的诊断的治疗决策。其次，虽然PPR的作者正确地认识到评估个人“暴露”的重要性，其中包括详细考虑个人因素，如社会经济地位、生活环境、创伤暴露、“生活方式”，来自包括肿瘤学在内的其他医学领域的经验表明，开发可靠的工具来评估这些在一生中进化的可变和动态实体是“极具挑战性的”（Wild 2005）。此外，PPR的作者强调了将生物标记物整合到精神病学实践中的关键重要性，这是精确精神病学路线图方法未来成功的基础：“没有生物标记物，精确精神病学的目标就无法实现”（Kas et al. 2025）。“生物标志物”可以定义为一种特征，可以作为正常生物过程、致病过程或对暴露或干预的生物反应的指标进行测量；在精神药物开发中，生物标志物可能是诊断、监测、预后、治疗鉴定以及耐受性和安全性考虑的基础。生物标志物的鉴定和评估促进了阿尔茨海默病的诊断、分期和药物开发，从而有助于美国食品和药物管理局批准针对淀粉样蛋白斑块的单克隆抗体作为该疾病的治疗方法（Harris 2023）。人们希望类似的进展能够促进用于其他神经精神疾病的化合物的开发和监管批准。这种成功的机会不仅取决于分析验证（即标记物准确地测量其声称要测量的内容，具有必要的敏感性和特异性）和临床验证（即标记物反映感兴趣的潜在过程，并在独立样本中具有预测有效性），这两者都由PPR作者强调，而且还取决于其他关键因素，如患者的可接受性，易于纳入常规临床实践，以及决定临床决策的成本效益。一个已确定的生物标志物只有在易于使用的情况下才会被广泛采用。 上述保留意见可能看起来有点粗鲁：毫无疑问，PPR是一项最有价值的倡议。它冷静而有说服力地呼吁在原则和程序上达成全球一致，在新兴数据的预测有效性上建立共识，并将新知识应用到不断发展的框架中，这为推进以前似乎是一个模糊领域的步骤提供了急需的清晰度。这组作者强调了在不同的诊断人群中协调研究评估和方法的重要性，认识到关键的第一步是与多个利益相关者的积极参与和双向沟通，同时承认潜在的障碍，例如国家之间基础设施的显着差异以及在不同研究地点收集的变量。波兰裔美国科学家和哲学家阿尔弗雷德·科尔日布斯基（Alfred Korzybski）提出了另一种隐喻表达，“地图不是领土”，旨在识别现实世界与我们所理解的世界之间的差异：世界地图与世界本身并不相同。路线图可以显示一个风景，包括所有的公路和障碍，高峰和低谷，但它本身并不是应许之地：然而，如果没有一个指导性的方向路线图，旅行者可能会停滞不前，或者有迷路的危险。因此，精确精神病学路线图（Kas et al. 2025）代表了一项重要的、协调一致的集体努力，将在多年内进行，应该得到所有对促进对精神健康问题的神经心理生物学的理解和开发导致改善临床结果的新治疗方法感兴趣的人的支持。David S. Baldwin是《人类精神药理学》的主编。Milica M. Nestorovic宣布没有利益冲突。
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Natalie J. Hughes-Medlicott, Hoang Nguyen, Paul Glue, Yoram Barak
Background
Postpartum depression (PPD) is associated with significant morbidity and mortality. It affects as many as 11.5% of women giving birth. Allopregnanolone (an endogenous progesterone metabolite) has been a promising avenue of clinical research for the treatment of PPD.
Aim
To assess the pharmacokinetics of allopregnanolone (Allo) following orally dosed progesterone in healthy volunteers. Secondary outcome was calculating the daily dose of progesterone needed to achieve the clinically meaningful concentration of 50 ng/mL Allo.
Methods
Single ascending dose study to measure plasma concentrations of Allo after 200, 400 and 600 mg doses of extended-release progesterone capsules. Secondary outcome was the safety and tolerability of extended-release progesterone capsules.
Results
We recruited 10 participants, 9 male and 1 female, mean (SD) age 38.7 (18.7) years. The maximum plasma concentration (Cmax) of Allo was observed at 2 h. A linear relationship was fitted to the observations. Sedation was assessed at baseline, 1, 2, 4, 6 and 8 h after each dose. Sedation ratings increased at 1–2 h post-dose after all three progesterone doses, with the greatest increase after the 600 mg dose, and fell subsequently. Vital signs were unchanged, and no other adverse events were reported.
Conclusions
In this single ascending dose study has clarified that 400 mg four times/day of progesterone is required to achieve maximum plasma ALLO concentrations of 50 ng/mL. Tolerability and safety were acceptable for all doses of progesterone tested.
{"title":"Allopregnanolone Concentrations After Ascending Single Dose Administration of Progesterone to Healthy Volunteers","authors":"Natalie J. Hughes-Medlicott, Hoang Nguyen, Paul Glue, Yoram Barak","doi":"10.1002/hup.70012","DOIUrl":"https://doi.org/10.1002/hup.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Postpartum depression (PPD) is associated with significant morbidity and mortality. It affects as many as 11.5% of women giving birth. Allopregnanolone (an endogenous progesterone metabolite) has been a promising avenue of clinical research for the treatment of PPD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the pharmacokinetics of allopregnanolone (Allo) following orally dosed progesterone in healthy volunteers. Secondary outcome was calculating the daily dose of progesterone needed to achieve the clinically meaningful concentration of 50 ng/mL Allo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single ascending dose study to measure plasma concentrations of Allo after 200, 400 and 600 mg doses of extended-release progesterone capsules. Secondary outcome was the safety and tolerability of extended-release progesterone capsules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We recruited 10 participants, 9 male and 1 female, mean (SD) age 38.7 (18.7) years. The maximum plasma concentration (<i>C</i><sub>max</sub>) of Allo was observed at 2 h. A linear relationship was fitted to the observations. Sedation was assessed at baseline, 1, 2, 4, 6 and 8 h after each dose. Sedation ratings increased at 1–2 h post-dose after all three progesterone doses, with the greatest increase after the 600 mg dose, and fell subsequently. Vital signs were unchanged, and no other adverse events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this single ascending dose study has clarified that 400 mg four times/day of progesterone is required to achieve maximum plasma ALLO concentrations of 50 ng/mL. Tolerability and safety were acceptable for all doses of progesterone tested.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Gabapentinoids are a group of medications used for treating patients with a limited range of neurological or psychiatric conditions: some (gabapentin and pregabalin) have entered widespread clinical use, due to their analgesic, anticonvulsant and anxiolytic effects. Licenced indications for these drugs vary across countries: for example, within the United Kingdom (UK), gabapentin does not have a market authorisation for treating patients with psychiatric disorders, although it is licenced for treatment of focal seizures, peripheral neuropathic pain, menopausal symptoms in women with breast cancer, oscillopsia and spasticity in multiple sclerosis, and muscular symptoms in motor neuron disease. By contrast, pregabalin has a license for generalized anxiety disorder (GAD), and for treating patients with peripheral or central neuropathic pain, and as an adjunctive therapy in patients with focal seizures: however, it is not licenced for GAD within the United States. Since introduction, gabapentin and pregabalin have become often prescribed outside the terms of their market authorisations in many countries: at least half of all gabapentinoid prescriptions in the UK may be ‘off-label’ [Montastruc et al. <span>2018</span>], and concerns regarding widespread non-prescribed use (with some fatalities) led to their reclassification as Class C controlled substances with accompanying regulations regarding prescriptions, in April 2019. Since this reclassification, further data on potential hazards associated with non-prescribed use of gabapentinoids have accumulated [Baldwin and Masdrakis <span>2022</span>].</p><p>Findings from epidemiological studies and systematic reviews indicate that the prevalence of non-prescribed gabapentinoid use is not insubstantial: for example, in populations without a history of substance misuse the prevalence of non-prescribed use of pregabalin may lie between 0.5% and 8.5% among those dispensed the drug [Schjerning et al. <span>2016</span>]. A range of risk factors for non-prescribed use for gabapentinoids have been identified: individuals with a history of substance use disorders are at greater risk, particularly those with a history of opiate use or poly-substance use. Other possible risk factors for non-prescribed use include younger age, male sex, a diagnosis of anxiety, access to multiple prescribers, and physical illness including cancer, multiple sclerosis and neuropathy [Driot et al. <span>2019</span>].</p><p>There are multiple hazards associated with non-prescribed use of gabapentinoids [Baldwin and Masdrakis <span>2022</span>]. Non-prescribed ‘overuse’ of gabapentin is associated with increased risks of all-cause and drug-related hospitalisation, particularly if combined with opioids, and pregabalin prescriptions in patients undergoing opioid maintenance therapy may increase all-cause mortality: increased risk of death may result from respiratory depression, prolonged gastrointestinal transit increasing gabapentin conc
加巴喷丁类药物是一组用于治疗范围有限的神经或精神疾病患者的药物：其中一些（加巴喷丁和普瑞巴林）由于其镇痛、抗惊厥和抗焦虑作用已进入广泛的临床应用。这些药物的许可适应症因国家而异：例如，在联合王国（UK），加巴喷丁没有用于治疗精神疾病患者的市场授权，尽管它被许可用于治疗局灶性癫痫发作、周围神经性疼痛、乳腺癌妇女的更年期症状、多发性硬化症的震颤和痉挛，以及运动神经元疾病的肌肉症状。相比之下，普瑞巴林被许可用于治疗广泛性焦虑症（GAD），治疗周围或中枢神经性疼痛患者，并作为局灶性癫痫患者的辅助治疗：然而，它在美国没有被许可用于治疗广泛性焦虑症。自引入以来，加巴喷丁和普瑞巴林在许多国家的市场授权条款之外经常被开处方：英国至少有一半的加巴喷丁类处方可能是“标签外的”[Montastruc等人，2018]，对广泛的非处方使用（造成一些死亡）的担忧导致它们在2019年4月被重新分类为C类受控物质，并伴有处方法规。自重新分类以来，关于非处方使用加巴喷丁类药物的潜在危害的进一步数据已经积累起来[Baldwin and Masdrakis 2022]。流行病学研究和系统评价的结果表明，非处方加巴喷丁类药物使用的患病率并非不高：例如，在没有药物滥用史的人群中，非处方使用普瑞巴林的患病率可能在0.5%至8.5%之间[Schjerning et al. 2016]。已经确定了非处方使用加巴喷丁类药物的一系列风险因素：有物质使用障碍史的个体风险更大，特别是有阿片类药物使用史或多种物质使用史的个体。其他可能的非处方使用风险因素包括年龄较小、男性、诊断为焦虑症、获得多个处方者以及身体疾病，包括癌症、多发性硬化症和神经病[Driot et al. 2019]。非处方使用加巴喷丁类药物有多种危害[Baldwin and Masdrakis 2022]。非处方“过度使用”加巴喷丁与全因和药物相关住院的风险增加有关，特别是如果与阿片类药物联合使用，并且在接受阿片类药物维持治疗的患者中使用普瑞巴林处方可能会增加全因死亡率：死亡风险增加可能是由于呼吸抑制、胃肠道转运时间延长、加巴喷丁浓度增加以及与注射阿片类药物相比，加巴喷丁起效延迟所致。加巴喷丁类药物使用者可能会增加“自杀行为”的风险[Yuen et al. 2025]，意外过量服用、道路交通事故、违法行为和头部/身体受伤[Molero et al. 2019]。非处方使用也可能与依赖和戒断综合征有关，但这些并没有很好地表征。可能的戒断症状包括焦虑、失眠、抑郁、躁动、易怒、“偏执”、精神病、自杀念头、头痛、关节和肌肉疼痛、嗜睡、发抖、出汗、心动过速、定向障碍和癫痫发作；可能的新生儿戒断综合症也被描述过。出现戒断症状的患者比例尚未确定，但在加巴喷丁突然停药后，大约有一半的病例出现躁动、精神错乱和定向障碍[Ashworth等人，2023]：即使在短疗程后也可能出现戒断症状。戒断症状通常在停药后24-48小时内出现，但也可能延迟至7天。苯二氮卓类药物依赖的临床管理建立在预防、早期识别和逐渐减少剂量与简单的心理支持措施相结合的基础上[Baldwin 2022]：尽管抗焦虑药物加巴喷丁类药物与苯二氮卓类药物具有不同的作用机制，但不能假设非处方使用加巴喷丁类药物以类似的方式得到最佳管理。临床管理非处方使用加巴喷丁类药物的首要原则必须包括对潜在风险的认识：精神卫生专业人员不应将加巴喷丁类药物视为良性抗焦虑药，应考虑其他替代方法，如心理治疗方法和不同的药物类别。 临床医生在考虑加巴喷丁类药物的处方时应考虑潜在的危害，并采取行动，通过仔细的风险评估，在首次处方前就与治疗相关的潜在风险进行咨询，谨慎开处方，协调一致地监测滥用迹象，防止非处方使用，并对诸如要求更高剂量、从多个提供者处获得处方和药物丢失报告等指标保持警惕。目前，关于加巴喷丁类药物的停药速度，或者伴随用药是否可以缓解停药过程，存在很多不确定性[Parsons 2018；Anderson et al. 2023]。这种不确定性需要通过研究、算法和审计来解决。建议稳定逐渐减少剂量，但支持加巴喷丁类药物长期“双曲逐渐减少”的证据极其有限。同时使用苯二氮卓类药物的报告产生了相互矛盾的发现，加巴喷丁类药物之间的转换似乎无效。病例报告表明，抗精神病药物在治疗戒断引起的谵妄方面有一定的益处。在目前缺乏明确证据的情况下，有必要警告患者不要突然停止治疗，鼓励患者在考虑退出治疗时加强他们的支持网络，以患者同意的速度减少剂量，考虑改用液体制剂以促进剂量逐渐减少，并在退出过程中定期审查进展。是《人类精神药理学》的主编。gl声明没有利益冲突。
{"title":"How Should Non-Prescribed Use of Gabapentinoids be Reduced in Psychiatric Practice?","authors":"Giada Lorenzi, David S. Baldwin","doi":"10.1002/hup.70010","DOIUrl":"https://doi.org/10.1002/hup.70010","url":null,"abstract":"<p>Gabapentinoids are a group of medications used for treating patients with a limited range of neurological or psychiatric conditions: some (gabapentin and pregabalin) have entered widespread clinical use, due to their analgesic, anticonvulsant and anxiolytic effects. Licenced indications for these drugs vary across countries: for example, within the United Kingdom (UK), gabapentin does not have a market authorisation for treating patients with psychiatric disorders, although it is licenced for treatment of focal seizures, peripheral neuropathic pain, menopausal symptoms in women with breast cancer, oscillopsia and spasticity in multiple sclerosis, and muscular symptoms in motor neuron disease. By contrast, pregabalin has a license for generalized anxiety disorder (GAD), and for treating patients with peripheral or central neuropathic pain, and as an adjunctive therapy in patients with focal seizures: however, it is not licenced for GAD within the United States. Since introduction, gabapentin and pregabalin have become often prescribed outside the terms of their market authorisations in many countries: at least half of all gabapentinoid prescriptions in the UK may be ‘off-label’ [Montastruc et al. <span>2018</span>], and concerns regarding widespread non-prescribed use (with some fatalities) led to their reclassification as Class C controlled substances with accompanying regulations regarding prescriptions, in April 2019. Since this reclassification, further data on potential hazards associated with non-prescribed use of gabapentinoids have accumulated [Baldwin and Masdrakis <span>2022</span>].</p><p>Findings from epidemiological studies and systematic reviews indicate that the prevalence of non-prescribed gabapentinoid use is not insubstantial: for example, in populations without a history of substance misuse the prevalence of non-prescribed use of pregabalin may lie between 0.5% and 8.5% among those dispensed the drug [Schjerning et al. <span>2016</span>]. A range of risk factors for non-prescribed use for gabapentinoids have been identified: individuals with a history of substance use disorders are at greater risk, particularly those with a history of opiate use or poly-substance use. Other possible risk factors for non-prescribed use include younger age, male sex, a diagnosis of anxiety, access to multiple prescribers, and physical illness including cancer, multiple sclerosis and neuropathy [Driot et al. <span>2019</span>].</p><p>There are multiple hazards associated with non-prescribed use of gabapentinoids [Baldwin and Masdrakis <span>2022</span>]. Non-prescribed ‘overuse’ of gabapentin is associated with increased risks of all-cause and drug-related hospitalisation, particularly if combined with opioids, and pregabalin prescriptions in patients undergoing opioid maintenance therapy may increase all-cause mortality: increased risk of death may result from respiratory depression, prolonged gastrointestinal transit increasing gabapentin conc","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maurizio Pompili, Maria Anna Trocchia, Ludovica Longhini, Eva Dispenza, Cristina Di Legge, Salvatore Sarubbi, Denise Erbuto, Isabella Berardelli
Objective
Treatment-resistant depression is one of the most significant clinical challenges in psychiatric practice. The primary aim of the present study was to assess the efficacy and tolerability of intranasal esketamine on depressive symptoms in a real-world outpatient setting. A secondary objective was to explore the potential benefits of intranasal esketamine on hopelessness and suicide risk (suicidal ideation and suicide attempts).
Methods
Twenty-one patients diagnosed with treatment-resistant depression were treated with intranasal esketamine. Depressive symptoms (MADRS and BDI), suicide risk (C-SSRS), and hopelessness (BHS) were assessed. We conducted a mixed model for repeated measures analysis to evaluate changes from baseline (T0), 3-month follow-up (T1), and 6-month follow-up (T2).
Results
Results indicated that depressive symptoms decreased over time. Specifically, both clinician and self-report measures show lower levels of depressive symptoms at 3-month and 6-month follow-up. We also found a significant decrease in the presence of suicidal ideation between T0 and T2. Finally, patients also reported a reduction in hopelessness levels over time.
Conclusions
Our findings indicate an overall response regarding depressive symptoms, hopelessness, and suicidal ideation after esketamine in treatment-resistant depression at 3-month and 6-month follow-up assessments.
{"title":"Efficacy of Intranasal Esketamine in Treatment-Resistant Depression: A Six-Month Real-World Follow-Up Study of Depressive Symptoms, Hopelessness, and Suicide Risk","authors":"Maurizio Pompili, Maria Anna Trocchia, Ludovica Longhini, Eva Dispenza, Cristina Di Legge, Salvatore Sarubbi, Denise Erbuto, Isabella Berardelli","doi":"10.1002/hup.70008","DOIUrl":"https://doi.org/10.1002/hup.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Treatment-resistant depression is one of the most significant clinical challenges in psychiatric practice. The primary aim of the present study was to assess the efficacy and tolerability of intranasal esketamine on depressive symptoms in a real-world outpatient setting. A secondary objective was to explore the potential benefits of intranasal esketamine on hopelessness and suicide risk (suicidal ideation and suicide attempts).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-one patients diagnosed with treatment-resistant depression were treated with intranasal esketamine. Depressive symptoms (MADRS and BDI), suicide risk (C-SSRS), and hopelessness (BHS) were assessed. We conducted a mixed model for repeated measures analysis to evaluate changes from baseline (T0), 3-month follow-up (T1), and 6-month follow-up (T2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Results indicated that depressive symptoms decreased over time. Specifically, both clinician and self-report measures show lower levels of depressive symptoms at 3-month and 6-month follow-up. We also found a significant decrease in the presence of suicidal ideation between T0 and T2. Finally, patients also reported a reduction in hopelessness levels over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate an overall response regarding depressive symptoms, hopelessness, and suicidal ideation after esketamine in treatment-resistant depression at 3-month and 6-month follow-up assessments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Levi J. M. Schuurman, Sjacko Sobczak, Julie E. M. Schulkens, Benno P. F. Balter, Sebastiaan P. J. van Alphen
Objective
Patient-reported side-effect questionnaires contribute to balanced decisions regarding treatment strategy among patients with mental health disorders. However, current side-effect questionnaires are less suitable for older adults because they often lack age-specific side effects. Therefore, the Scale for Subjective Somatic and Cognitive Complaints of Psychotropic Medication Adult-Aged-Spectrum (SCOPA) was developed to quantify psychotropic side effects across the full adult age spectrum. The aim of this study was to develop and evaluate the reliability and validity of the SCOPA.
Procedures
Psychometric properties of the SCOPA were assessed in a Dutch patient population (n = 205, age 18–86 years) and a general population (n = 281, age 18–87 years). Reliability of the subscales was measured through average inter-item correlation and Cronbach's alphas. Construct validity was analysed by exploratory factor analysis.
Results
Average inter-item correlation and Cronbach's alphas of the subscales of the SCOPA were moderate to good. Exploratory factor analyses supported a two-factor solution, labelled as complaints in somatic and cognitive domains.
Conclusions
This study showed that the SCOPA has promising psychometric qualities and practical capability to evaluate the side-effect burden of treatment with psychotropic medication across the adult-aged-spectrum. However, more research is needed to cross-validate these results in the field's pursuit of increased patient safety.
{"title":"Psychometric Properties of the Scale for Subjective Somatic and Cognitive Complaints of Psychotropic Medication Adult-Aged-Spectrum (SCOPA)","authors":"Levi J. M. Schuurman, Sjacko Sobczak, Julie E. M. Schulkens, Benno P. F. Balter, Sebastiaan P. J. van Alphen","doi":"10.1002/hup.70009","DOIUrl":"https://doi.org/10.1002/hup.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Patient-reported side-effect questionnaires contribute to balanced decisions regarding treatment strategy among patients with mental health disorders. However, current side-effect questionnaires are less suitable for older adults because they often lack age-specific side effects. Therefore, the Scale for Subjective Somatic and Cognitive Complaints of Psychotropic Medication Adult-Aged-Spectrum (SCOPA) was developed to quantify psychotropic side effects across the full adult age spectrum. The aim of this study was to develop and evaluate the reliability and validity of the SCOPA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Procedures</h3>\u0000 \u0000 <p>Psychometric properties of the SCOPA were assessed in a Dutch patient population (<i>n</i> = 205, age 18–86 years) and a general population (<i>n</i> = 281, age 18–87 years). Reliability of the subscales was measured through average inter-item correlation and Cronbach's alphas. Construct validity was analysed by exploratory factor analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Average inter-item correlation and Cronbach's alphas of the subscales of the SCOPA were moderate to good. Exploratory factor analyses supported a two-factor solution, labelled as complaints in somatic and cognitive domains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study showed that the SCOPA has promising psychometric qualities and practical capability to evaluate the side-effect burden of treatment with psychotropic medication across the adult-aged-spectrum. However, more research is needed to cross-validate these results in the field's pursuit of increased patient safety.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hup.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sonali Karhana, Samra Hussain, Mohammad Mateen Zehgeer, Mohd. Ashif Khan
Aim
This systematic review aimed to evaluate the efficacy of zopiclone as a potent positive control for the assessment of residual effects of hypnotic drugs on the next day driving performance in clinical trials.
Methodology
Online databases and websites were used to conduct a literature search to identify relevant clinical trials encompassing the use of zopiclone as a positive control and the trials examining the residual effects of zopiclone on the next day driving performance. A total of 22 articles were identified and as per the inclusion criteria, 16 were selected for final data retrieval.
Results
The average difference in Standard Deviation of Lateral Position (SDLP) between zopiclone and a placebo ranged from 1.6 to 4.74 cm. On average, this difference was about 2.51 cm, indicating significant impairment in driving ability the day after taking zopiclone. Therefore, current studies demonstrate zopiclone administration impairs driving performance, as indicated by increased standard deviation of lateral position (SDLP) values. Additionally, the reported adverse events included somnolence, dyspepsia, fatigue, headache, dizziness, gastrointestinal disorders, and upper respiratory tract problems.
Conclusion
Zopiclone can serve as a reliable positive control in future clinical trials assessing the residual effects of hypnotic drugs on next-day driving performance.
{"title":"Zopiclone as a Potent Positive Control for Assessing the Residual Effects of Hypnotic Drugs on Next Day Driving Performance: A Systematic Review","authors":"Sonali Karhana, Samra Hussain, Mohammad Mateen Zehgeer, Mohd. Ashif Khan","doi":"10.1002/hup.70007","DOIUrl":"https://doi.org/10.1002/hup.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This systematic review aimed to evaluate the efficacy of zopiclone as a potent positive control for the assessment of residual effects of hypnotic drugs on the next day driving performance in clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Online databases and websites were used to conduct a literature search to identify relevant clinical trials encompassing the use of zopiclone as a positive control and the trials examining the residual effects of zopiclone on the next day driving performance. A total of 22 articles were identified and as per the inclusion criteria, 16 were selected for final data retrieval.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average difference in Standard Deviation of Lateral Position (SDLP) between zopiclone and a placebo ranged from 1.6 to 4.74 cm. On average, this difference was about 2.51 cm, indicating significant impairment in driving ability the day after taking zopiclone. Therefore, current studies demonstrate zopiclone administration impairs driving performance, as indicated by increased standard deviation of lateral position (SDLP) values. Additionally, the reported adverse events included somnolence, dyspepsia, fatigue, headache, dizziness, gastrointestinal disorders, and upper respiratory tract problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Zopiclone can serve as a reliable positive control in future clinical trials assessing the residual effects of hypnotic drugs on next-day driving performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 4","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Due to its short plasma half-life, clozapine is typically prescribed in a divided dosing regimen. Although once-daily dosing has proven effective in countries such as Japan, South Korea, Canada, and the United States, its adoption in real-world clinical practice in China remains unclear. This study aimed to compare patient characteristics, psychiatric symptoms, side effects, and plasma clozapine concentrations between once-daily and divided dosing regimens, and to determine the dosage required to achieve plasma levels of 350–600 ng/mL in the Chinese population.
Methods
We conducted a single-center, retrospective, cross-sectional study at Xi'an Mental Health Center, China, collecting data on clozapine-treated patients from March 2019 to March 2021.
Results
Most patients (80% of 198) in the Chinese cohort followed a divided-dose regimen in clinical practice. In the once-daily dosing group, the average plasma clozapine concentration was 158.75 ng/mL, with only 8% of patients reaching the therapeutic window. Conversely, patients on a divided dosing regimen had significantly higher plasma concentrations, averaging 373.34 ng/mL, with 28% within the therapeutic window. The psychiatric symptom remission rate did not differ significantly between the once-daily and divided-dosing groups (50.05% vs. 52.72%, p = 0.718); however, the divided-dosing group experienced a greater variety of adverse effects. Receiver operating characteristic analysis indicated that patients on multiple daily doses require a total daily clozapine dose of 150–250 mg to achieve the target plasma concentration, corresponding to a clozapine concentration-to-dose ratio of 1.4–2.4.
Conclusions
Chinese clinicians generally adhere to a divided dosing schedule for clozapine when the daily dose exceeds 50 mg. Further prospective longitudinal studies are warranted to evaluate whether once-daily dosing regimens can improve clinical outcomes.
由于氯氮平的血浆半衰期短，通常采用分次给药方案。尽管每日一次的剂量在日本、韩国、加拿大和美国等国家已被证明是有效的，但在中国的实际临床实践中，其采用情况仍不清楚。本研究旨在比较每日一次和分次给药方案之间的患者特征、精神症状、副作用和血浆氯氮平浓度，并确定在中国人群中达到350-600 ng/mL血浆水平所需的剂量。方法我们在中国西安精神卫生中心进行了一项单中心、回顾性、横断面研究，收集了2019年3月至2021年3月氯氮平治疗患者的数据。结果在临床实践中，中国队列中大多数患者（198例中的80%）采用分次给药方案。在每日一次给药组中，氯氮平平均血浆浓度为158.75 ng/mL，只有8%的患者达到治疗窗口期。相反，采用分次给药方案的患者血浆浓度明显较高，平均为373.34 ng/mL，其中28%在治疗窗内。每日一次给药组和分次给药组的精神症状缓解率无显著差异（50.05% vs 52.72%, p = 0.718）；然而，分组给药组出现了更多的不良反应。受试者工作特征分析表明，每日多次给药的患者需要每日氯氮平总剂量150 ~ 250mg才能达到目标血药浓度，对应的氯氮平浓度剂量比为1.4 ~ 2.4。结论当氯氮平日剂量超过50mg时，我国临床医生普遍采用分次给药方案。需要进一步的前瞻性纵向研究来评估每日一次给药方案是否能改善临床结果。
{"title":"Clozapine Once-Versus Multiple-Daily Dosing Regimen: A Single-Center, Retrospective, Cross-Sectional Study","authors":"Jing Ding, Suo Zhang, Huan Xing, Luyao Li","doi":"10.1002/hup.70006","DOIUrl":"https://doi.org/10.1002/hup.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Due to its short plasma half-life, clozapine is typically prescribed in a divided dosing regimen. Although once-daily dosing has proven effective in countries such as Japan, South Korea, Canada, and the United States, its adoption in real-world clinical practice in China remains unclear. This study aimed to compare patient characteristics, psychiatric symptoms, side effects, and plasma clozapine concentrations between once-daily and divided dosing regimens, and to determine the dosage required to achieve plasma levels of 350–600 ng/mL in the Chinese population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a single-center, retrospective, cross-sectional study at Xi'an Mental Health Center, China, collecting data on clozapine-treated patients from March 2019 to March 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most patients (80% of 198) in the Chinese cohort followed a divided-dose regimen in clinical practice. In the once-daily dosing group, the average plasma clozapine concentration was 158.75 ng/mL, with only 8% of patients reaching the therapeutic window. Conversely, patients on a divided dosing regimen had significantly higher plasma concentrations, averaging 373.34 ng/mL, with 28% within the therapeutic window. The psychiatric symptom remission rate did not differ significantly between the once-daily and divided-dosing groups (50.05% vs. 52.72%, <i>p</i> = 0.718); however, the divided-dosing group experienced a greater variety of adverse effects. Receiver operating characteristic analysis indicated that patients on multiple daily doses require a total daily clozapine dose of 150–250 mg to achieve the target plasma concentration, corresponding to a clozapine concentration-to-dose ratio of 1.4–2.4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Chinese clinicians generally adhere to a divided dosing schedule for clozapine when the daily dose exceeds 50 mg. Further prospective longitudinal studies are warranted to evaluate whether once-daily dosing regimens can improve clinical outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13030,"journal":{"name":"Human Psychopharmacology: Clinical and Experimental","volume":"40 3","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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