酸枣仁汤合黄连温胆汤治疗成人慢性失眠症及辅助苯二氮卓类药物撤药的作用: 一项多中心、前瞻性队列研究

杨思雨; 冷秀梅; 刘晋; 徐文华; 袁勇贵; 孙丽霞; 李勇; 侯正华; 徐治; 戴恒; 陈素珍; 伊恩; 杜心雨; 徐心然; 仲瑾; 张静; 吴婷; 汪秀琴

doi:10.14148/j.issn.1672-0482.2023.1224

文章导航 > 南京中医药大学学报 > 2023 > 39(12): 1224-1231

杨思雨, 冷秀梅, 刘晋, 徐文华, 袁勇贵, 孙丽霞, 李勇, 侯正华, 徐治, 戴恒, 陈素珍, 伊恩, 杜心雨, 徐心然, 仲瑾, 张静, 吴婷, 汪秀琴. 酸枣仁汤合黄连温胆汤治疗成人慢性失眠症及辅助苯二氮卓类药物撤药的作用: 一项多中心、前瞻性队列研究[J]. 南京中医药大学学报, 2023, 39(12): 1224-1231. doi: 10.14148/j.issn.1672-0482.2023.1224

引用本文:

YANG Si-yu, LENG Xiu-mei, LIU Jin, XU Wen-hua, YUAN Yong-gui, SUN Li-xia, LI Yong, HOU Zheng-hua, XU Zhi, DAI Heng, CHEN Su-zhen, JAN D. Reinhardt, DU Xin-yu, XU Xin-ran, ZHONG Jin, ZHANG Jing, WU Ting, WANG Xiu-qin. Treatment of Adult Chronic Insomnia and the Effect of Assisting Benzodiazepine Withdrawl with a Combination of Suanzaoren Decoction and Huanglian Wendan Decoction: A Multicenter, Prospective Cohort Study[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(12): 1224-1231. doi: 10.14148/j.issn.1672-0482.2023.1224

Citation:

YANG Si-yu, LENG Xiu-mei, LIU Jin, XU Wen-hua, YUAN Yong-gui, SUN Li-xia, LI Yong, HOU Zheng-hua, XU Zhi, DAI Heng, CHEN Su-zhen, JAN D. Reinhardt, DU Xin-yu, XU Xin-ran, ZHONG Jin, ZHANG Jing, WU Ting, WANG Xiu-qin. Treatment of Adult Chronic Insomnia and the Effect of Assisting Benzodiazepine Withdrawl with a Combination of Suanzaoren Decoction and Huanglian Wendan Decoction: A Multicenter, Prospective Cohort Study[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(12): 1224-1231. doi: 10.14148/j.issn.1672-0482.2023.1224

引用本文:

Citation:

YANG Si-yu, LENG Xiu-mei, LIU Jin, XU Wen-hua, YUAN Yong-gui, SUN Li-xia, LI Yong, HOU Zheng-hua, XU Zhi, DAI Heng, CHEN Su-zhen, JAN D. Reinhardt, DU Xin-yu, XU Xin-ran, ZHONG Jin, ZHANG Jing, WU Ting, WANG Xiu-qin. Treatment of Adult Chronic Insomnia and the Effect of Assisting Benzodiazepine Withdrawl with a Combination of Suanzaoren Decoction and Huanglian Wendan Decoction: A Multicenter, Prospective Cohort Study[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(12): 1224-1231. doi: 10.14148/j.issn.1672-0482.2023.1224

酸枣仁汤合黄连温胆汤治疗成人慢性失眠症及辅助苯二氮卓类药物撤药的作用: 一项多中心、前瞻性队列研究

doi: 10.14148/j.issn.1672-0482.2023.1224

杨思雨^1,,
冷秀梅²,
刘晋³,
徐文华⁴,
袁勇贵⁵,
孙丽霞⁶,
李勇⁷,
侯正华⁵,
徐治⁵,
戴恒⁶,
陈素珍⁵,
伊恩^{8, 9, 10},
杜心雨¹,
徐心然¹,
仲瑾¹,
张静¹,
吴婷¹,
汪秀琴^{2, 4, ,}

1.
南京医科大学第一附属医院/江苏省人民医院神经内科, 江苏南京 210029
2.
南京医科大学第一附属医院/江苏省人民医院中医科, 江苏南京 210029
3.
南京医科大学第一附属医院/江苏省人民医院科技处, 江苏南京 210029
4.
南京医科大学第一附属医院/江苏省人民医院国际合作处, 江苏南京 210029
5.
东南大学附属中大医院心理精神科, 江苏南京 210009
6.
南京中医药大学第一临床医学院, 江苏南京 210029
7.
南京医科大学第一附属医院/江苏省人民医院医学心理科, 江苏南京 210029
8.
四川大学灾后重建与管理学院, 四川成都 610207
9.
南京医科大学第一附属医院/江苏省人民医院康复医学科, 江苏南京 210029
10.
卢塞恩大学健康科学与医学系, 卢塞恩州卢塞恩市 6009

基金项目:

江苏省中医药科技发展专项 2020ZX19

江苏省人民医院(南京医科大学第一附属医院)临床能力提升工程项目 JSPH-MA-2022-7

国家自然科学基金面上项目 81772454

国家自然科学基金面上项目 81971237

详细信息

作者简介:
杨思雨, 女, 医师, E-mail: 15195969298@163.com

通讯作者:
汪秀琴, 女, 主任中医师, 主要从事失眠、消化系统等疾病的中医临床治疗及研究, E-mail: xiuqinw@126.com

中图分类号: R285.6
计量
- 文章访问数: 158
- HTML全文浏览量: 20
- PDF下载量: 26
- 被引次数: 0
出版历程
- 收稿日期: 2023-10-23
- 网络出版日期: 2023-12-20
- 发布日期: 2023-12-10

Treatment of Adult Chronic Insomnia and the Effect of Assisting Benzodiazepine Withdrawl with a Combination of Suanzaoren Decoction and Huanglian Wendan Decoction: A Multicenter, Prospective Cohort Study

1.
Department of Neurology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
2.
Department of Traditional Chinese Medicine, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
3.
Science and Technology Department, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
4.
Department of International Cooperation, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
5.
Department of Psychiatry, Zhongda Hospital, Southeast University, Nanjing 210009, China
6.
The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210029, China
7.
Department of Medical Psychology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
8.
Institute for Disaster Management and Reconstruction, Sichuan University, Chengdu 610207, China
9.
Department of Rehabilitation Medicine, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
10.
Department of Health Science and Medicine, University of Lucerne, Lucerne 6009, Switzerland

摘要

摘要: 目的观察酸枣仁汤合黄连温胆汤对成人慢性失眠症的疗效以及对镇静催眠药撤药的影响。方法纳入187名慢性失眠症患者进行分析, 其中中医组102人, 西医组85人, 中医组予酸枣仁汤合黄连温胆汤治疗, 西医组在医生指导下服用苯二氮卓类镇静催眠药治疗。干预时间为1个月, 干预前和干预结束予匹兹堡睡眠质量指数(PSQI)评估, 并在干预结束后3个月和6个月进行随访。结果 2组患者基线资料无明显差异。干预结束后, 2组患者PSQI评分均有显著改善(P < 0.01), 中医组在睡眠质量、催眠药物及总分下降方面优于西医组(P < 0.01)。线性回归分析结果显示, 在控制混杂因素后, 中医组在2个不同的模型中回归系数分别是1.821和1.922, 前者具有统计学意义(P < 0.05)。筛选中医组基线服用镇静催眠药的患者, 与西医组比较镇静催眠药撤药的影响因素，3个月随访时中医组39例患者中有25例撤药, 西医组80例患者中17例撤药(χ²=19.25, P < 0.001);6个月随访时中医组39例患者中有23例撤药, 西医组79例患者中18例撤药(χ²=13.53, P < 0.001), 中医组撤药率明显高于西医组。进一步回归分析结果显示, 在调整混杂因素后, 组别结果显示西医组在3个月(OR=5.50, 95%CI: 2.30~13.72)和6个月(OR=6.43, 95%CI: 2.54~17.77)未撤药的比值明显高于中医组, 结果具有统计学差异(P < 0.05)。结论酸枣仁汤合黄连温胆汤对慢性失眠症疗效明显, 并具有辅助镇静催眠药撤药的作用。
- 慢性失眠症 /
- 匹兹堡睡眠量表 /
- 镇静催眠药撤药 /
- 中医药
Abstract: OBJECTIVE To explore the efficacy of Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction on adult chronic insomnia and its effect on hypnotic withdrawal. METHODS 187 patients with chronic insomnia were included for analysis, including 102 in the traditional Chinese medicine (TCM) group and 85 in the western medicine group. The TCM group was treated with Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction, while the western medicine group was treated with benzodiazepine under the consideration of doctor. The intervention period was 1 month, with assessments using the Pittsburgh Sleep Quality Index (PSQI) conducted before and after the intervention. Follow-up evaluations were performed at 3 months and 6 months respectively after the intervention. RESULTS There was no significant difference between the two groups at baseline. After the intervention, the PSQI scores of patients in both groups were significantly improved (P < 0.01). Among them, the TCM group was better than the western medicine group in the improvement of sleep quality and sleeping pills, total PSQI score reduction (P < 0.01). The results of linear regression analysis showed that after controlling for confounding factors, the regression coefficients of the TCM group in two different models were1.821 and 1.922 respectively, and the former was statistically significant (P < 0.05). By screening patients who took hypnotics at baseline in the TCM group and comparing them with those in the western medicine group, the influencing factors of hypnotic withdrawal were analyzed. During the 3-month follow-up, 25 out of 39 patients in the TCM group and 17 out of 80 patients in the western medicine group had hypnotic withdrawal (χ²= 19.25, P < 0.001); during the 6-month follow-up, 23 of the 39 patients in the TCM group and 18 of the 79 patients in the western medicine group had hypnotic withdrawal (χ²= 13.53, P < 0.001), the withdrawal rate of patients in the TCM group was significantly higher than that in the western medicine group. Further regression analysis showed that after adjusting for confounding factors, the results showed that the western medicine group had a significantly higher rate of not withdrawal than the TCM group at 3 months (OR=5.50, 95%CI: 2.30~13.72) and 6 months (OR=6.43, 95%CI: 2.54~17.77), and the results were statistically different (P < 0.05). CONCLUSION Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction is effective in treating adult chronic insomnia and assisting in hypnotic withdrawal.
- chronic insomnia /
- Pittsburgh Sleep Quality Index /
- hypnotic withdrawal /
- traditional Chinese medicine

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图 1 研究流程图

Figure 1. Flow chart of study

下载: 全尺寸图片幻灯片

图 2 不同阶段镇静催眠药撤药的影响因素分析

Figure 2. Analysis of factors affecting hypnotic withdrawl at different time points

下载: 全尺寸图片幻灯片

图 3 2组患者不同时间点镇静催眠药撤药情况

Figure 3. Hypnotic withdrawl status of participants between two groups at different time points

下载: 全尺寸图片幻灯片

表 1 2组基线信息比较[M(P₂₅, P₇₅)]

Table 1. Baseline characteristics of participants [M(P₂₅, P₇₅)]

组别	例数	性别		年龄/岁	病程/月	PSQI评分
组别	例数	男	女	年龄/岁	病程/月	PSQI评分
中医组	102	32	70	45.00 [33.25, 55.75]	24.00 [12.00, 60.00]	15.00 [12.00, 16.00]
西医组	85	18	67	52.00 [37.00, 63.00]	24.00 [8.00, 60.00]	13.00 [12.00, 16.00]

组别	例数	文化程度/%			生活习惯/%
组别	例数	高中及以下	大学本科及以上		无	有
中医组	102	42(41.1)	60(58.9)		84(82.4)	18(17.6)
西医组	85	47(55.3)	38(44.7)		69(81.2)	16(18.8)
注: 生活习惯指有无饮茶、酒和咖啡。

下载: 导出CSV

表 2 2组PSQI评分比较[M(P₂₅, P₇₅)]

Table 2. Comparisons of PSQI between two groups [M(P₂₅, P₇₅)]

组别	例数	时间	总分	睡眠质量	入睡时间	睡眠时间
中医组	102	治疗前	15.0 [12.0, 16.0]	3.0 [2.0, 3.0]	3.0 [2.0, 3.0]	2.5 [1.0, 3.0]
		治疗后	7.8 [5.0, 9.8]^{** ##}	1.0 [1.0, 1.5]^{** ##}	1.5 [1.0, 2.0]^**	1.0 [0.6, 1.6]^**
西医组	85	治疗前	13.0 [12.0, 16.0]	2.0 [2.0, 3.0]	3.0 [2.0, 3.0]	2.0[1.0, 3.0]
		治疗后	9.0 [7.0, 11.0]^**	1.0 [1.0, 2.0]^**	1.6 [1.0, 3.0]^**	1.6 [1.0, 3.0]^**

组别	例数	时间	睡眠效率	睡眠障碍	催眠药物	日间功能障碍
中医组	102	治疗前	3.0 [1.0, 3.0]	1.0 [1.0, 2.0]	0 [0, 3.0]	3.0 [1.0, 3.0]
		治疗后	1.0 [0, 2.0]^**	1.0 [1.0, 1.0]^**	0 [0, 1.4]^{** ##}	1.0 [0, 1.2]^**
西医组	85	治疗前	2.0 [0, 3.0]	2.0 [1.0, 2.0]	3.0 [1.0, 3.0]	2.0 [2.0, 3.0]
		治疗后	1.0 [0, 1.0]^**	1.0 [1.0, 1.0]^**	3.0 [2.0, 3.0]^**	1.0 [0.8, 1.0]^**
注: 组内比较, ^**P < 0.01;组间比较，^##P < 0.01。

下载: 导出CSV

表 3 PSQI评分影响因素分析

Table 3. Analysis of factors affecting PSQI

	组别	β	Se(β)	t	P
模型1	中医组(单纯中药)	1.821	0.630	2.889	0.004
	中医组(中药合并西药)	2.084	0.656	3.178	0.002
模型2	中医组(单纯中药)	1.922	1.015	1.893	0.060
	中医组(中药合并西药)	2.080	0.702	2.962	0.003

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参考文献(31)

[1]	RIEMANN D, BENZ F, DRESSLE RJ, et al. Insomnia disorder: State of the science and challenges for the future[J]. J Sleep Res, 2022, 31(4): e13604. doi: 10.1111/jsr.13604
[2]	RIEMANN D, BAGLIONI C, BASSETTI C, et al. European guideline for the diagnosis and treatment of insomnia[J]. J Sleep Res, 2017, 26(6): 675-700. doi: 10.1111/jsr.12594
[3]	PERLIS ML, POSNER D, RIEMANN D, et al. Insomnia[J]. Lancet, 2022, 400(10357): 1047-1060. doi: 10.1016/S0140-6736(22)00879-0
[4]	中国睡眠研究会. 中国失眠症诊断和治疗指南[J]. 中华医学杂志, 2017, 97(24): 1844-1856. doi: 10.3760/cma.j.issn.0376-2491.2017.24.002 Chinese Sleep Research Association. Chinese guidelines for diagnosis and treatment of insomnia[J]. Natl Med J China, 2017, 97(24): 1844-1856. doi: 10.3760/cma.j.issn.0376-2491.2017.24.002
[5]	CHAN NY, CHAN JWY, LI SX, et al. Non-pharmacological approaches for management of insomnia[J]. Neurotherapeutics, 2021, 18(1): 32-43. doi: 10.1007/s13311-021-01029-2
[6]	LANZA G, FISICARO F, CANTONE M, et al. Repetitive transcranial magnetic stimulation in primary sleep disorders[J]. Sleep Med Rev, 2023, 67: 101735. doi: 10.1016/j.smrv.2022.101735
[7]	SATEIA MJ, BUYSSE DJ, KRYSTAL AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American academy of sleep medicine clinical practice guideline[J]. J Clin Sleep Med, 2017, 13(2): 307-349. doi: 10.5664/jcsm.6470
[8]	SOYKA M. Treatment of benzodiazepine dependence[J]. N Engl J Med, 2017, 376(24): 2399-2400.
[9]	VICENS C, BEJARANO F, SEMPERE E, et al. Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: Cluster randomised controlled trial in primary care[J]. Br J Psychiatry, 2014, 204(6): 471-479. doi: 10.1192/bjp.bp.113.134650
[10]	徐文华, 徐海鹏, 吴婷, 等. 中医药辨证治疗失眠的临床疗效[J]. 江苏医药, 2021, 47(3): 256-259. doi: 10.19460/j.cnki.0253-3685.2021.03.010 XU WH, XU HP, WU T, et al. Efficacy of traditional Chinese medicine dialectical therapy in patients with insomnia[J]. Jiangsu Med J, 2021, 47(3): 256-259. doi: 10.19460/j.cnki.0253-3685.2021.03.010
[11]	中华医学会神经病学分会, 中华医学会神经病学分会睡眠障碍学组. 中国成人失眠诊断与治疗指南(2017版)[J]. 中华神经科杂志, 2018, 51(5): 324-35. https://www.cnki.com.cn/Article/CJFDTOTAL-XDJB201305005.htm Chinese Society of Neurology, Sleep Disorders Group of the Neurology Branch of the Chinese Medical Association. China adult insomnia diagnosis and treatment guidelines (2017 edition)[J]. Chin J Neurol, 2018, 51(5): 324-335. https://www.cnki.com.cn/Article/CJFDTOTAL-XDJB201305005.htm
[12]	张伯礼, 吴勉华, 林子强. 中医内科学[M]. 北京: 中国中医药出版社, 2019. ZHANG BL, WU MH, LIN ZQ. Chinese Internal Medicine[M]. Beijing: China press of traditional Chinese medicine, 2019.
[13]	PUUSTINEN J, LA HTEENMA KI R, POLO-KANTOLA P, et al. Effect of withdrawal from long-term use of temazepam, zopiclone or zolpidem as hypnotic agents on cognition in older adults[J]. Eur J Clin Pharmacol, 2014, 70(3): 319-329. doi: 10.1007/s00228-013-1613-6
[14]	CHAN YY, CHEN YH, YANG SN, et al. Clinical efficacy of traditional Chinese medicine, Suan Zao Ren Tang, for sleep disturbance during methadone maintenance: A randomized, double-blind, placebo-controlled trial[J]. Evid Based Complement Alternat Med, 2015, 2015: 710895.
[15]	荣润国, 钟家辉, 林少萍, 等. 改良酸枣仁汤治疗原发性失眠随机安慰剂对照试验[J]. 中国心理卫生杂志, 2017, 31(8): 606-613. doi: 10.3969/j.issn.1000-6729.2017.08.005 RONG RG, ZHONG JH, LIN SP, et al. A randomized placebo-controlled trial on the treatment of primary insomnia with modified Suanzaoren Decoction[J]. Chin Ment Heath J, 2017, 31(8): 606-613. doi: 10.3969/j.issn.1000-6729.2017.08.005
[16]	XIE CL, GU Y, WANG WW, et al. Efficacy and safety of Suanzaoren Decoction for primary insomnia: A systematic review of randomized controlled trials[J]. BMC Complement Altern Med, 2013, 13: 18. doi: 10.1186/1472-6882-13-18
[17]	YI PL, TSAI CH, CHEN YC, et al. Gamma-aminobutyric acid (GABA) receptor mediates suanzaorentang, a traditional Chinese herb remedy, -induced sleep alteration[J]. J Biomed Sci, 2007, 14(2): 285-297. doi: 10.1007/s11373-006-9137-z
[18]	YI PL, LIN CP, TSAI CH, et al. The involvement of serotonin receptors in suanzaorentang-induced sleep alteration[J]. J Biomed Sci, 2007, 14(6): 829-840. doi: 10.1007/s11373-007-9197-8
[19]	HUA Y, GUO S, XIE H, et al. Ziziphus jujuba mill. var. spinosa (bunge) hu ex H. F. Chou seed ameliorates insomnia in rats by regulating metabolomics and intestinal flora composition[J]. Front Pharmacol, 2021, 12: 653767. doi: 10.3389/fphar.2021.653767
[20]	MA Y, HAN HS, EUN JS, et al. Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems[J]. Biol Pharm Bull, 2007, 30(9): 1748-1753. doi: 10.1248/bpb.30.1748
[21]	WANG LE, CUI XY, CUI SY, et al. Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors[J]. Phytomedicine, 2010, 17(6): 404-409. doi: 10.1016/j.phymed.2010.01.014
[22]	HUANGFU YR, PENG W, GUO BJ, et al. Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial[J]. J Integr Med, 2019, 17(3): 161-166. doi: 10.1016/j.joim.2019.01.007
[23]	WANG LY, SONG YH, LI F, et al. Effects of Wen Dan Tang on insomnia-related anxiety and levels of the brain-gut peptide Ghrelin[J]. Neural Regen Res, 2014, 9(2): 205-212. doi: 10.4103/1673-5374.125351
[24]	ZHAN LH, DONG YJ, YANG K, et al. Soporific effect of modified Suanzaoren Decoction and its effects on the expression of CCK-8 and orexin-A[J]. Evid Based Complement Alternat Med, 2020, 2020: 6984087.
[25]	LEI YANG, LIYUN HE, XIAO CHEN, et al. Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance[J]. Digit Chin Med, 2022, 5(3): 340-352. doi: 10.1016/j.dcmed.2022.10.010
[26]	刘兰, 张远哲, 陈铭. 基于网络药理学探讨黄连温胆汤治疗失眠的作用机制[J]. 医学信息, 2023, 36(3): 10-14. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXX202303003.htm LIU L, ZHANG YZ, CHEN M. The mechanism of Huanglian Wendan Decoction in the treatment of insomnia based on network pharmacology[J]. J Med Inf, 2023, 36(3): 10-14. https://www.cnki.com.cn/Article/CJFDTOTAL-YXXX202303003.htm
[27]	李亮, 王珠强, 胡莹, 等. 基于神经递质和5-HT_1A/Gα_i/o/cAMP信号通路研究黄连温胆汤对失眠大鼠的治疗作用及机制[J]. 中药新药与临床药理, 2023, 34(5): 591-598. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXY202305012.htm LI L, WANG ZQ, HU Y, et al. Exploring the therapeutic effect and mechanism of Huanglian Wendan Decoction on insomnia rats based on neurotransmitter and 5-HT_1A/Gα_i/o/cAMP signaling pathway[J]. Tradit Chin Drug Res Clin Pharmacol, 2023, 34(5): 591-598. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXY202305012.htm
[28]	HOOD SD, NORMAN A, HINCE DA, et al. Benzodiazepine dependence and its treatment with low dose flumazenil[J]. Br J Clin Pharmacol, 2014, 77(2): 285-294.
[29]	LUSCHER C, UNGLESS MA. The mechanistic classification of addictive drugs[J]. PLoS Med, 2006, 3(11): e437.
[30]	TAN KR, BROWN M, LABOUèBE G, et al. Neural bases for addictive properties of benzodiazepines[J]. Nature, 2010, 463(7282): 769-774.
[31]	FERNANDES M, NEVES I, OLIVEIRA J, et al. Discontinuation of chronic benzodiazepine use in primary care: A nonrandomized intervention[J]. Fam Pract, 2022, 39(2): 241-248.