Moscou Timo T, Veerman Selene R T
Department of Community Mental Health, Mental Health Service Noord-Holland Noord, Alkmaar, Oude Hoeverweg 10, Noord Holland 1816 BT, The Netherlands.
Department of Community Mental Health, Mental Health Service Noord-Holland Noord, Alkmaar, The Netherlands.
Ther Adv Psychopharmacol. 2024 Dec 7;14:20451253241302603. doi: 10.1177/20451253241302603. eCollection 2024.
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.
To review the literature on the effect of the CLO/NCLO ratio on cognitive functioning in patients with SSD.
This is a systematic review.
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.
We identified 15 relevant studies (longitudinal, = 4; cross-sectional, = 11). The study population consisted of adult clozapine users ( = 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: = 2, cross-sectional: = 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 ( = 11). No significant correlations were found between the CLO/NCLO ratio and the cognitive domains processing speed, reasoning/problem solving, or for working memory ( = 1, = 11), verbal learning ( = 1, = 43) or visual learning ( = 2, = 54). Study designs and populations were heterogeneous, and the analysis of confounding factors was limited and inconsistent.
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.
This systematic review was preregistered with PROSPERO (CRD42023385244).
目前关于难治性精神分裂症（TRS）认知功能的研究有限且质量不高。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）与认知功能改善之间的关联并不一致。活性代谢物去甲氯氮平（NCLO）可能因其胆碱能和谷氨酸能活性而发挥促认知作用。遗憾的是，关于CLO/NCLO比值与认知功能的研究更为稀少。
综述关于CLO/NCLO比值对SSD患者认知功能影响的文献。
这是一项系统综述。
在电子数据库Embase、PsycINFO、PubMed、Cochrane以及Cochrane对照试验注册库中进行检索，对语言和出版年份无限制。
我们确定了15项相关研究（纵向研究 = 4项；横断面研究 = 11项）。研究人群包括不同程度治疗抵抗的成年氯氮平使用者（n = 953）。分别使用各种神经心理学测试和综合评分评估特定认知领域和整体认知功能。11项研究质量一般（纵向研究 = 2项，横断面研究 = 9项）。在一项纵向研究中，发现CLO/NCLO比值与注意力/警觉性之间存在负因果关系，社会认知与综合评分之间存在负相关（n = 11）。未发现CLO/NCLO比值与认知领域处理速度、推理/解决问题或工作记忆（n = 1，n = 11）、言语学习（n = 1，n = 43）或视觉学习（n = 2，n = 54）之间存在显著相关性。研究设计和人群具有异质性，对混杂因素的分析有限且不一致。
临床证据过于稀少，无法支持NCLO具有促认知作用的假设。通过调节CLO/NCLO比值进行个性化氯氮平治疗仍遥不可及。讨论了未来氯氮平研究的建议和预期局限性。
本系统综述已在PROSPERO（CRD42023385244）上预先注册。
