Efficacy and Safety of Risperidone Microspheres for Injection (Ⅱ) in the Treatment of Patients with Acute Schizophrenia

doi:10.12114/j.issn.1007-9572.2023.0224

Chinese General Practice ›› 2023, Vol. 26 ›› Issue (32): 4007-4012.DOI: 10.12114/j.issn.1007-9572.2023.0224

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Efficacy and Safety of Risperidone Microspheres for Injection (Ⅱ) in the Treatment of Patients with Acute Schizophrenia

1. Peking University Sixth Hospital/Peking University Institute of Mental Health/NHC Key Laboratory of Mental Health (Peking University) /National Clinical Research Center for Mental Disorders, Beijing 100191, China
2. Hebei Provincial Mental Health Center/Hebei Key Laboratory of Major Mental and Behavioral Disorders/the Sixth Clinical Medical College of Hebei University, Baoding 071000, China
3. The Fourth People's Hospital in Urumqi, Urumqi 830002, China
4. Taiyuan Psychiatric Hospital, Taiyuan 030045, China
5. Tianjin Anding Hospital, Tianjin 300222, China

Received:2023-03-27 Revised:2023-06-05 Published:2023-11-15 Online:2023-06-30
Contact: SI Tianmei

注射用利培酮微球（Ⅱ）治疗急性期精神分裂症患者的疗效及安全性研究

1．100191　北京市，北京大学第六医院　北京大学精神卫生研究所　国家卫生健康委员会精神卫生学重点实验室（北京大学）　国家精神心理疾病临床医学研究中心
2．071000　河北省保定市，河北省精神卫生中心　河北省重大精神与行为障碍疾病研究重点实验室　河北大学第六临床医学院
3．830002　新疆维吾尔自治区乌鲁木齐市第四人民医院
4．030045　山西省太原市精神病医院
5．300222　天津市安定医院

通讯作者: 司天梅
作者简介:
作者贡献：李茜负责数据整理与分析，论文初稿撰写；严保平、王健、王媛、秦英杰、孙俊伟、邓怀丽、曲雪慧、周楠负责病例筛选、数据管理；张云淑、马燕娟、那龙、任智勇、马宏筠负责项目策划，整体执行和管理；司天梅负责项目总体设计、文章质量控制和审校。

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Abstract

Abstract:

Background

Long-acting antipsychotics are currently important therapeutic options for the long-term treatment of schizophrenia. Risperidone microspheres for injection (Ⅱ) has been modified in dosage form to ensure fast acting without oral antipsychotic supplementation during treatment, however, there is a lack of studies on the efficacy and safety of it.

Objective

To evaluate the efficacy and safety of risperidone microspheres for injection (Ⅱ) in patients with acute schizophrenia.

Methods

This is a single-arm multicenter prospective study. The patients aged 18-55 years with acute schizophrenia from August 2021 to April 2022 at five study centers including Peking University Sixth Hospital, Hebei Provincial Mental Health Center, the Fourth People's Hospital in Urumqi, Taiyuan Psychiatric Hospital and Tianjin Anding Hospital were included and given variable dose of risperidone microspheres for injection (Ⅱ) of 25.0 mg/2 weeks, 37.5 mg/2 weeks or 50.0 mg/2 weeks and followed up for 8 weeks. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI-S) and the Udvalg for Kliniske Undersogelser (UKU) Side Effects Rating Scale were used for evaluation at baseline and the end of week 2, 4, 6 and 8. In addition, Personal and Social Performance (PSP) Scale were evaluated and laboratory tests were collected at baseline and the end of week 8.

Results

A total of 58 patients were included in the study. PANSS total score, PANSS-positive score, PANSS-negative score, PANSS-general psychopathology score and CGI-S score were significantly reduced at the end of week 2, 4, 6 and 8 compared to baseline (P<0.001). The effective rates of PANSS total score reduction were 37.9% (22/58), 70.7% (41/58), 89.7% (52/58) and 89.7% (52/58) at the end of week 2, 4, 6 and 8, respectively. The PSP score at the end of week 8 (71.00±14.99) was higher than at baseline (46.28±15.43) (P<0.001). The average plasma concentration was (12.94±8.47), (13.23±10.86), (21.09±13.04), (23.64±14.23) and (29.08±19.51) μg/L at the end of week 1, 2, 4, 6 and 8, respectively. Common adverse reactions included tremor, dystonia, and constipation, all of which ranged from mild to moderate, with no serious adverse reactions or discontinuations due to no adverse reactions. Plasma prolactin (PRL) level was increased at the end of week 8 compared with baseline (P<0.05) .

Conclusion

Risperidone microspheres for injection (Ⅱ) can act fast without oral antipsychotic supplementation and effectively improve the multi-dimensional symptoms of acute schizophrenia with acceptable tolerance.

Key words: Schizophrenia, Antipsychotic agents, Long-acting antipsychotics, Risperidone microspheres for injection (Ⅱ), Treatment outcome, Drug-related side effects and adverse reactions

摘要：

背景

长效抗精神病药是目前精神分裂症全病程治疗中的重要选择之一。注射用利培酮微球（Ⅱ）在剂型上进行了改良，治疗期间无需补充口服药物，能够快速起效，但目前尚缺少其临床疗效的相关研究。

目的

评估注射用利培酮微球（Ⅱ）治疗急性期精神分裂症患者的疗效及安全性。

方法

本研究为单臂多中心前瞻性研究，纳入2021年8月—2022年4月北京大学第六医院、河北省精神卫生中心、乌鲁木齐市第四人民医院、太原市精神病医院、天津市安定医院5个研究中心，18~55岁急性期精神分裂症患者为研究对象，给予25.0 mg/2周、37.5 mg/2周或50.0 mg/2周可变剂量注射用利培酮微球（Ⅱ）治疗，随访8周。分别在基线和2、4、6、8周末进行阳性与阴性症状量表（PANSS）、临床总体印象量表（CGI）及精神科药物不良反应量表（UKU）评定。于基线及8周末进行个人和社会功能量表（PSP）评定，并采集患者实验室检查指标。

结果

研究共纳入58例患者。治疗2、4、6、8周末患者PANSS总分、阳性症状量表分、阴性症状量表分、一般精神病理量表分、CGI-疾病严重程度（CGI-S）评分均较基线降低（P<0.001）；2、4、6周及8周末患者PANSS总分减分有效率分别为37.9%（22/58）、70.7%（41/58）、89.7%（52/58）和89.7%（52/58）。治疗8周末PSP评分〔（71.00±14.99）分〕高于基线〔（46.28±15.43）分〕（P<0.001）。患者的平均血药浓度在1、2、4、6、8周末分别达到（12.94±8.47）、（13.23±10.86）、（21.09±13.04）、（23.64±14.23）、（29.08±19.51）μg/L。常见不良反应包括震颤、肌张力障碍、便秘等，均为轻度到中度，无严重不良反应及因无不良反应脱落者。治疗8周末泌乳素水平较基线升高（P<0.05）。

结论

注射用利培酮微球（Ⅱ）可在不补充口服抗精神病药的情况下快速起效，可有效改善精神分裂症急性期的多维度症状，且耐受性良好。

关键词: 精神分裂症, 抗精神病药, 长效抗精神病药, 注射用利培酮微球（Ⅱ）, 治疗结果, 药物相关性副作用和不良反应

LI Qian,ZHANG Yunshu,YAN Baoping, et al. Efficacy and Safety of Risperidone Microspheres for Injection (Ⅱ) in the Treatment of Patients with Acute Schizophrenia[J]. Chinese General Practice, 2023, 26(32): 4007-4012. DOI: 10.12114/j.issn.1007-9572.2023.0224.
李茜,张云淑,严保平等. 注射用利培酮微球（Ⅱ）治疗急性期精神分裂症患者的疗效及安全性研究[J]. 中国全科医学, 2023, 26(32): 4007-4012. DOI: 10.12114/j.issn.1007-9572.2023.0224.

Figures/Tables 4

References 26

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用药时间	例数	25.0 mg	37.5 mg	50.0 mg
基线	58	31（53.4）	26（44.8）	1（1.7）
2周末	57	12（21.1）	32（56.1）	13（22.8）
4周末	56	19（33.9）	23（41.1）	14（25.0）
6周末	55	17（30.9）	25（45.5）	13（23.6）

用药时间	例数	25.0 mg	37.5 mg	50.0 mg
基线	58	31（53.4）	26（44.8）	1（1.7）
2周末	57	12（21.1）	32（56.1）	13（22.8）
4周末	56	19（33.9）	23（41.1）	14（25.0）
6周末	55	17（30.9）	25（45.5）	13（23.6）

用药时间	例数	PANSS总分	阳性症状量表	阴性症状量表	一般精神病理量表	CGI-S^b
基线	58	92.52±16.79	25.69±6.02	23.88±6.03	42.95±9.50	5.34±0.61
2周末	58	80.12±18.40^a	21.62±5.57^a	21.16±5.96^a	37.34±9.72^a	4.84±0.72^a
4周末	58	66.41±16.74^a	17.41±4.87^a	17.21±5.46^a	31.79±8.72^a	4.05±0.77^a
6周末	58	57.03±18.03^a	13.50±5.10^a	15.57±5.87^a	27.97±8.66^a	3.27±1.03^a
8周末	58	53.81±18.71^a	12.34±5.03^a	14.86±5.66^a	26.60±9.23^a	3.00±0.92^a
F值		178.857	154.948	103.829	127.222	125.308
P值		<0.001	<0.001	<0.001	<0.001	<0.001

用药时间	例数	PANSS总分	阳性症状量表	阴性症状量表	一般精神病理量表	CGI-S^b
基线	58	92.52±16.79	25.69±6.02	23.88±6.03	42.95±9.50	5.34±0.61
2周末	58	80.12±18.40^a	21.62±5.57^a	21.16±5.96^a	37.34±9.72^a	4.84±0.72^a
4周末	58	66.41±16.74^a	17.41±4.87^a	17.21±5.46^a	31.79±8.72^a	4.05±0.77^a
6周末	58	57.03±18.03^a	13.50±5.10^a	15.57±5.87^a	27.97±8.66^a	3.27±1.03^a
8周末	58	53.81±18.71^a	12.34±5.03^a	14.86±5.66^a	26.60±9.23^a	3.00±0.92^a
F值		178.857	154.948	103.829	127.222	125.308
P值		<0.001	<0.001	<0.001	<0.001	<0.001

指标	例数	基线	8周末	Z（t）值	P值
BMI（kg/m²）	53	24.03±4.48	24.99±4.84	-4.031^a	<0.001
腰围（cm）	53	85.45±16.50	87.03±17.59	-3.639^a	0.001
TC〔M（P₂₅，P₇₅），mmol/L〕	53	4.00（3.61，4.72）	4.30（3.65，5.14）	-1.448	0.148
TG〔M（P₂₅，P₇₅），mmol/L〕	53	1.13（0.76，1.76）	1.60（1.03，1.83）	-1.680	0.093
HDL-C〔M（P₂₅，P₇₅），mmol/L〕	53	1.13（0.96，1.31）	1.11（0.95，1.36）	-0.874	0.382
LDL-C〔M（P₂₅，P₇₅），mmol/L〕	53	2.33（2.06，2.76）	2.40（2.08，2.95）	-0.025	0.980
FBG〔M（P₂₅，P₇₅），mmol/L〕	53	4.85（4.51，5.40）	4.80（4.42，5.26）	-0.089	0.929
PRL〔M（P₂₅，P₇₅），mU/L〕	53	549.10（332.73，1 622.55）	1 327.76（565.24，2 995.67）	-3.618	<0.001

Efficacy and Safety of Risperidone Microspheres for Injection (Ⅱ) in the Treatment of Patients with Acute Schizophrenia

注射用利培酮微球（Ⅱ）治疗急性期精神分裂症患者的疗效及安全性研究

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