摘要
难治性精神分裂症约占精神分裂症患者的30%,其复杂的病理机制涉及多巴胺-谷氨酸能失衡、神经炎症及表观遗传异常,导致传统单一靶点药物疗效不足。氯氮平是该病唯一推荐的二线治疗药物,但约半数患者仍存在应答不足及粒细胞缺乏、代谢综合征等严重不良反应。为此,氯氮平联合疗法成为突破治疗瓶颈的重要策略。研究显示,氯氮平与抗精神病药物联用可通过多受体协同作用改善阴性症状及认知功能,同时降低代谢不良反应风险,与抗抑郁药或心境稳定剂联用可调节单胺能及谷氨酸通路,缓解共病情感症状,在非药物疗法中,经颅磁刺激(TMS)和电休克治疗(ECT)通过神经调控增强疗效,认知行为疗法(CBT)则提升治疗依从性。未来方向聚焦于开发纳米载体、透皮贴剂等新型递送系统以提高药物靶向性,并利用人工智能整合多模态数据优化个体化治疗,以改善难治性精神分裂症患者的预后。
Treatment-resistant schizophrenia affects approximately 30%of schizophrenia patients.Its complex pathogenesis involves dopamine-glutamate dysregulation,neuroinflammation,and epigenetic abnormalities,leading to insufficient efficacy of conventional single-target antipsychotics.Clozapine remains the only recommended second-line treatment for TRS.However,approximately half of patients exhibit suboptimal responses or experience severe adverse effects,including agranulocytosis and metabolic syndrome.Consequently,clozapine-based combination therapies have emerged as a critical strategy to overcome therapeutic limitations.Studies demonstrate that combining clozapine with other antipsychotics synergistically modulates multiple receptors,significantly improving negative symptoms and cognitive function while reducing metabolic risks.Augmentation with antidepressants or mood stabilizers regulates monoaminergic and glutamatergic pathways,alleviating comorbid affective symptoms.Among non-pharmacological interventions,transcranial magnetic stimulation and electroconvulsive therapy enhance efficacy via neuromodulation,while cognitive behavioral therapy improves treatment adherence.Future research will focus on developing novel delivery systems(e.g.,nanocarriers,transdermal patches)to enhance drug targeting and leveraging artificial intelligence to integrate multimodal data for personalized treatment optimization,aiming to improve outcomes in TRS patients.
作者
徐鹏
蒋芬芳
周超男
Xu Peng;Jiang Fenfang;Zhou Chaonan(Department of Psychiatry,Dongyang Seventh People's Hospital,Dongyang,Zhejiang 322118,China)
出处
《中国药物与临床》
2025年第19期1287-1292,共6页
Chinese Remedies & Clinics
关键词
精神分裂症
难治性
氯氮平
联合疗法
安全性
Schizophrenia,treatment-resistant
Clozapine
Combination therapy
Safety
