Jarab Anan, Al-Qerem Walid, Khdour Adam, Awadallah Heba, Mimi Yousef, Khdour Maher
College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan.
Eur J Clin Pharmacol. 2025 Apr;81(4):525-541. doi: 10.1007/s00228-025-03809-7. Epub 2025 Feb 14.
Schizophrenia is a chronic and debilitating neuropsychiatric disorder affecting approximately 1% of the global population. Traditional antipsychotic treatments, while effective for positive symptoms, often have significant side effects and fail to address cognitive and negative symptoms. Novel pharmacological treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic pathways, and glutamate modulation have emerged as promising alternatives.
This systematic literature review aims to critically evaluate the efficacy, safety, and mechanisms of action of novel pharmacological agents in the treatment of schizophrenia.
A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Scopus, and Web of Science for randomized controlled trials (RCTs) and clinical trials published between April 2014 and March 2024. Studies evaluating novel treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic agents, and glutamate modulation were included. Primary outcomes focused on symptom reduction and quality of life, while secondary outcomes included cognitive function and adverse events. The Joanna Briggs Institute (JBI) tool was used for quality assessment.
Eleven studies involving 4614 participants (mean age 37-43 years, predominantly male) were included. Drugs evaluated included xanomeline-trospium (KarXT), pimavanserin, ulotaront, emraclidine, and bitopertin. Significant improvements in PANSS and CGI-S scores were observed, with xanomeline-trospium showing a mean reduction of 17.4 points (p < 0.001). Adverse events were mostly mild and transient, with nausea, constipation, and somnolence being common.
Novel treatments for schizophrenia show promise in managing both positive and negative symptoms, with generally favorable safety profiles. Future studies should focus on large-scale, long-term trials to refine their efficacy, safety, and clinical applicability.
精神分裂症是一种慢性且使人衰弱的神经精神疾病，影响着全球约1%的人口。传统抗精神病药物治疗虽对阳性症状有效，但往往有显著副作用，且无法解决认知和阴性症状。针对毒蕈碱受体、TAAR1激动剂、血清素能通路和谷氨酸调节的新型药物治疗已成为有前景的替代方案。
本系统文献综述旨在严格评估新型药物制剂治疗精神分裂症的疗效、安全性及作用机制。
在PubMed、Embase、Cochrane图书馆、Scopus和科学网全面检索2014年4月至2024年3月发表的随机对照试验（RCT）和临床试验。纳入评估针对毒蕈碱受体、TAAR1激动剂、血清素能药物和谷氨酸调节的新型治疗的研究。主要结局集中在症状减轻和生活质量，次要结局包括认知功能和不良事件。采用乔安娜·布里格斯研究所（JBI）工具进行质量评估。
纳入11项研究，涉及4614名参与者（平均年龄37 - 43岁，以男性为主）。评估的药物包括 xanomeline - trospium（KarXT）、匹莫范色林、乌洛托品、埃莫拉西定和比特佩汀。观察到阳性和阴性症状量表（PANSS）及临床总体印象量表严重程度（CGI - S）评分有显著改善，xanomeline - trospium平均降低17.4分（p < 0.001）。不良事件大多轻微且短暂，常见的有恶心、便秘和嗜睡。
精神分裂症的新型治疗在管理阳性和阴性症状方面显示出前景，总体安全性良好。未来研究应聚焦于大规模、长期试验，以优化其疗效、安全性和临床适用性。
