{"title":"精神分裂症谱系障碍患者氯氮平/去甲氯氮平血浆水平比与认知功能：一项系统综述。","authors":"Timo T Moscou, Selene R T Veerman","doi":"10.1177/20451253241302603","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Extant research on cognitive functioning in treatment-resistant schizophrenia (TRS) is limited and of poor quality. Cognitive impairments in patients with schizophrenia spectrum disorders (SSD) significantly influence quality of life. In patients with TRS, clozapine (CLO) is not consistently associated with improved cognitive functioning. The active metabolite n-desmethylclozapine (norclozapine (NCLO)) potentially exerts procognitive effects due to cholinergic and glutamatergic activity. Unfortunately, research on CLO/NCLO ratio and cognitive functioning is even more scarce.</p><p><strong>Objectives: </strong>To review the literature on the effect of the CLO/NCLO ratio on cognitive functioning in patients with SSD.</p><p><strong>Design: </strong>This is a systematic review.</p><p><strong>Data sources and methods: </strong>A search was carried out in the electronic databases Embase, PsycINFO, PubMed, Cochrane and the Cochrane Controlled Register of Trials with no restrictions in language or publication year.</p><p><strong>Results: </strong>We identified 15 relevant studies (longitudinal, <i>k</i> = 4; cross-sectional, <i>k</i> = 11). The study population consisted of adult clozapine users (<i>n</i> = 953) with varying degrees of treatment resistance. Specific cognitive domains and overall cognitive functioning were assessed using various neuropsychological tests and a composite score, respectively. Eleven studies were considered of fair quality (longitudinal: <i>k</i> = 2, cross-sectional: <i>k</i> = 9). In one longitudinal study, a negative causal relationship was found between the CLO/NCLO ratio and attention/vigilance and a negative correlation between social cognition and the composite score (<i>n</i> = 11). No significant correlations were found between the CLO/NCLO ratio and the cognitive domains processing speed, reasoning/problem solving, or for working memory (<i>k</i> = 1, <i>n</i> = 11), verbal learning (<i>k</i> = 1, <i>n</i> = 43) or visual learning (<i>k</i> = 2, <i>n</i> = 54). Study designs and populations were heterogeneous, and the analysis of confounding factors was limited and inconsistent.</p><p><strong>Conclusion: </strong>Clinical evidence is too scarce to support the hypothesis of a procognitive effect of NCLO. Personalised CLO treatment by modulating the CLO/NCLO ratio remains a distant prospect. Recommendations for future CLO research and anticipated limitations are discussed.</p><p><strong>Trial registration: </strong>This systematic review was preregistered with PROSPERO (CRD42023385244).</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"14 ","pages":"20451253241302603"},"PeriodicalIF":3.4000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624563/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clozapine/norclozapine plasma level ratio and cognitive functioning in patients with schizophrenia spectrum disorders: a systematic review.\",\"authors\":\"Timo T Moscou, Selene R T Veerman\",\"doi\":\"10.1177/20451253241302603\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Extant research on cognitive functioning in treatment-resistant schizophrenia (TRS) is limited and of poor quality. Cognitive impairments in patients with schizophrenia spectrum disorders (SSD) significantly influence quality of life. In patients with TRS, clozapine (CLO) is not consistently associated with improved cognitive functioning. The active metabolite n-desmethylclozapine (norclozapine (NCLO)) potentially exerts procognitive effects due to cholinergic and glutamatergic activity. Unfortunately, research on CLO/NCLO ratio and cognitive functioning is even more scarce.</p><p><strong>Objectives: </strong>To review the literature on the effect of the CLO/NCLO ratio on cognitive functioning in patients with SSD.</p><p><strong>Design: </strong>This is a systematic review.</p><p><strong>Data sources and methods: </strong>A search was carried out in the electronic databases Embase, PsycINFO, PubMed, Cochrane and the Cochrane Controlled Register of Trials with no restrictions in language or publication year.</p><p><strong>Results: </strong>We identified 15 relevant studies (longitudinal, <i>k</i> = 4; cross-sectional, <i>k</i> = 11). The study population consisted of adult clozapine users (<i>n</i> = 953) with varying degrees of treatment resistance. Specific cognitive domains and overall cognitive functioning were assessed using various neuropsychological tests and a composite score, respectively. 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引用次数: 0
摘要
背景：目前对难治性精神分裂症（TRS）认知功能的研究有限且质量较差。精神分裂症谱系障碍（SSD）患者的认知障碍显著影响生活质量。在TRS患者中，氯氮平（CLO）与认知功能的改善并不一致。活性代谢物n-去甲基氯氮平（去氯氮平（NCLO））可能由于胆碱能和谷氨酸能活性而发挥促进认知的作用。遗憾的是，关于CLO/NCLO比率与认知功能的研究更是少之又少。目的：回顾有关慢性阻塞性脑卒中患者CLO/NCLO比值对认知功能影响的文献。设计：这是一个系统的回顾。数据来源和方法：检索电子数据库Embase、PsycINFO、PubMed、Cochrane和Cochrane Controlled Register of Trials，无语言和出版年份限制。结果：我们确定了15项相关研究(纵向，k = 4；横截面，k = 11)。研究人群包括有不同程度治疗耐药性的氯氮平成年使用者（n = 953）。具体认知领域和整体认知功能分别使用各种神经心理学测试和综合评分进行评估。11项研究被认为质量尚可（纵向：k = 2，横断面：k = 9）。在一项纵向研究中，发现CLO/NCLO比率与注意/警惕性呈负相关，社会认知与综合得分呈负相关（n = 11）。CLO/NCLO比率与认知领域处理速度、推理/问题解决、工作记忆（k = 1, n = 11）、语言学习（k = 1, n = 43）或视觉学习（k = 2, n = 54）之间无显著相关性。研究设计和人群是异质的，混杂因素的分析是有限和不一致的。结论：临床证据太少，不足以支持NCLO有促进认知作用的假设。通过调节CLO/NCLO比率来个性化CLO治疗仍然是一个遥远的前景。讨论了对未来CLO研究的建议和预期的局限性。试验注册：本系统评价已在PROSPERO进行预注册（CRD42023385244）。
Clozapine/norclozapine plasma level ratio and cognitive functioning in patients with schizophrenia spectrum disorders: a systematic review.
Background: Extant research on cognitive functioning in treatment-resistant schizophrenia (TRS) is limited and of poor quality. Cognitive impairments in patients with schizophrenia spectrum disorders (SSD) significantly influence quality of life. In patients with TRS, clozapine (CLO) is not consistently associated with improved cognitive functioning. The active metabolite n-desmethylclozapine (norclozapine (NCLO)) potentially exerts procognitive effects due to cholinergic and glutamatergic activity. Unfortunately, research on CLO/NCLO ratio and cognitive functioning is even more scarce.
Objectives: To review the literature on the effect of the CLO/NCLO ratio on cognitive functioning in patients with SSD.
Design: This is a systematic review.
Data sources and methods: A search was carried out in the electronic databases Embase, PsycINFO, PubMed, Cochrane and the Cochrane Controlled Register of Trials with no restrictions in language or publication year.
Results: We identified 15 relevant studies (longitudinal, k = 4; cross-sectional, k = 11). The study population consisted of adult clozapine users (n = 953) with varying degrees of treatment resistance. Specific cognitive domains and overall cognitive functioning were assessed using various neuropsychological tests and a composite score, respectively. Eleven studies were considered of fair quality (longitudinal: k = 2, cross-sectional: k = 9). In one longitudinal study, a negative causal relationship was found between the CLO/NCLO ratio and attention/vigilance and a negative correlation between social cognition and the composite score (n = 11). No significant correlations were found between the CLO/NCLO ratio and the cognitive domains processing speed, reasoning/problem solving, or for working memory (k = 1, n = 11), verbal learning (k = 1, n = 43) or visual learning (k = 2, n = 54). Study designs and populations were heterogeneous, and the analysis of confounding factors was limited and inconsistent.
Conclusion: Clinical evidence is too scarce to support the hypothesis of a procognitive effect of NCLO. Personalised CLO treatment by modulating the CLO/NCLO ratio remains a distant prospect. Recommendations for future CLO research and anticipated limitations are discussed.
Trial registration: This systematic review was preregistered with PROSPERO (CRD42023385244).
期刊介绍：
Therapeutic Advances in Psychopharmacology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of psychopharmacology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in psychopharmacology, providing a forum in print and online for publishing the highest quality articles in this area.
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