氨磺必利联合氯氮平治疗精神分裂症：剂量优化与疗效评估的个体化治疗研究

Amisulpride combined with clozapine in the treatment of schizophrenia: A personalized therapeutic study on dose optimization and efficacy evaluation

摘要:

目的 探讨在精神分裂症治疗中，氨磺必利联合氯氮平方案的剂量优化策略及其对疗效和安全性的影响，为实现个体化治疗提供临床依据。方法 选取2021年1月—2024年11月山东省戴庄医院精神科收治的102例精神分裂症患者为研究对象，采用随机数字表法分为A组（常规剂量氯氮平）、B组（常规剂量氯氮平+常规剂量氨磺必利）和C组（低剂量氯氮平+常规剂量氨磺必利），各34例。3组疗程均为12周，比较3组治疗12周后的剂量调整情况、临床疗效及安全性［不良反应发生率（TESS）评分］，治疗前后精神症状［阳性和阴性症状量表（PANSS）评分］、社会功能［人与社会功能量表（PSP）］、认知功能［MATRICS成套测试共识版量表（MCCB）］及精神疾病相关递质［多巴胺（DA）与5-羟色胺（5-HT）］水平。结果 A组氯氮平基线剂量与最终剂量均高于B组和C组（P <0.05）。B组氨磺必利基线剂量高于C组（P <0.05）。B组剂量调整率高于A组和C组（P <0.05）。3组总有效率比较，差异无统计学意义（P >0.05）。B组和C组治疗前后PANSS中阴性症状、一般精神病理维度及总分的差值均大于A组（P <0.05），B组治疗前后PANSS中阳性症状维度评分的差值大于A组和C组（P <0.05）。C组治疗前后PSP、MCCB评分的差值均大于A组和B组（P <0.05）。C组治疗前后DA、5-HT水平的差值均大于B组和A组（P <0.05）。B组不良反应总发生率高于A组和C组（P <0.05）。结论 氨磺必利联合氯氮平治疗精神分裂症可显著改善精神症状、社会功能和认知功能，并能有效调节DA和5-HT水平。低剂量氯氮平联合方案在保持与常规剂量联合方案相当疗效的同时，显著减少剂量调整需求，并降低不良反应发生率。该方案通过优化用药剂量，在确保疗效的基础上提高了治疗安全性，适合于个体化治疗中对副作用有较高敏感性的患者，可为精神分裂症患者提供更精细化的治疗选择。

Abstract:

Objective To explore the dose optimization strategy of amisulpride combined with clozapine in the treatment of schizophrenia and its impact on efficacy and safety, so as to provide clinical evidence for personalized treatment.Methods A total of 102 patients with schizophrenia admitted to the Department of Psychiatry at Daizhuang Hospital from January 2021 to November 2024 were enrolled. They were assigned into the Group A (standard-dose clozapine, n = 34), Group B (standard-dose clozapine plus standard-dose amisulpride, n = 34), and Group C (low-dose clozapine plus standard-dose amisulpride, n = 34) using the random number table method. All groups underwent a 12-week treatment course. Comparisons among the three groups were made regarding dose adjustments, clinical efficacy, and safety [Treatment Emergent Symptom Scale (TESS) scores] after 12 weeks of treatment, and psychiatric symptoms [Positive and Negative Syndrome Scale (PANSS) scores], social functioning [Personal and Social Performance (PSP) scale], cognitive function [MATRICS Consensus Cognitive Battery (MCCB) scores], and neurotransmitter levels [dopamine (DA) and 5-hydroxytryptamine (5-HT) ] before and after treatment.Results Group A had higher baseline and final doses of clozapine compared to Groups B and C (P < 0.05). Group B had a higher baseline dose of amisulpride than Group C (P < 0.05). The dose adjustment rate in Group B was higher than that in Groups A and C (P < 0.05). There was no statistically significant difference in the overall effective rate among the three groups (P > 0.05). The differences in PANSS negative symptoms, general psychopathology, and total scores before and after treatment were greater in Groups B and C than in Group A (P < 0.05). The difference in PANSS positive symptoms scores before and after treatment was greater in Group B than in Groups A and C (P < 0.05). The differences in PSP and MCCB scores before and after treatment were greater in Group C than in Groups A and B (P < 0.05). The differences in DA and 5-HT levels before and after treatment were greater in Group C than in Groups B and A (P < 0.05). The overall incidence of adverse reactions in Group B was higher than that in Groups A and C (P < 0.05).Conclusion The combination of amisulpride and clozapine significantly improves psychiatric symptoms, social functioning, and cognitive performance while effectively modulating DA and 5-HT levels. The low-dose clozapine regimen maintained comparable efficacy to standard-dose combinations while reducing dose adjustment needs and adverse events. This optimized dosing strategy enhances treatment safety without compromising efficacy, making it particularly suitable for patients with heightened sensitivity to side effects and offering a refined therapeutic approach for schizophrenia.