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浙江大学学报(医学版)  2022, Vol. 51 Issue (4): 480-490    DOI: 10.3724/zdxbyxb-2022-0145
meta分析     
抗抑郁药物治疗儿童青少年抑郁症疗效和耐受性的网状meta分析
饶燕晓1,杨荣旺1,*(),赵京2,曹庆久3
1. 浙江大学医学院附属儿童医院心理科 国家儿童健康与疾病临床医疗研究中心 国家儿童区域医疗中心, 浙江 杭州 310052
2. 中国人民解放军联勤保障部队第九八四医院脑四科,北京 100094
3. 北京大学精神卫生研究所,北京 100083
Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis
RAO Yanxiao1,YANG Rongwang1,*(),ZHAO Jing2,CAO Qingjiu3
1. Department of Psychology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Regional Medical Center for Children, Hangzhou 310052, China;
2. The Fourth Department of Brain Medicine, the 984th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Beijing 100094, China;
3. Institute of Mental Health, Peking University, Beijing 100083, China
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摘要:

目的:比较多种抗抑郁药治疗儿童青少年抑郁症的效果,为儿童青少年抑郁症的治疗提供疗效与耐受性方面的依据。 方法:在PubMed、Cochrane Library、EMBASE、Web of Science、PsycINFO、中国生物医学文献数据库、中国知网和万方数据知识服务平台等数据库中检索关于抗抑郁药治疗儿童青少年抑郁症的随机对照试验,检索时间截至2021年12月。对纳入文献进行质量评价及数据提取,采用Stata 15.1软件对有效率、耐受性进行分析,采用累积排序概率曲线下面积(SUCAR)评估药物有效率和耐受性的累积概率。 结果:最终纳入32篇文献的33项随机对照试验研究,共6949例患者,涉及阿米替林、维拉唑酮、氟西汀、司来吉兰、帕罗西汀、丙咪嗪、地昔帕明、舍曲林、去甲替林、艾司西酞普兰、西酞普兰、文拉法辛、度洛西汀等13种抗抑郁药。网状meta分析结果显示,度洛西汀( OR=1.95, 95% CI: 1.41~2.69)、氟西汀( OR=1.73,95% CI:1.40~2.14)、文拉法辛( OR=1.37, 95% CI: 1.04~1.80)、艾司西酞普兰( OR=1.48,95% CI:1.12~1.95)的有效率显著高于安慰剂(均 P<0.05),网状meta的累积概率排序为度洛西汀(87.0%)、阿米替林(83.3%)、氟西汀(79.0%)、艾司西酞普兰(62.7%)等。丙咪嗪(OR=0.15,95% CI:0.08~0.27)、舍曲林( OR=0.33, 95% CI: 0.16~0.71)、文拉法辛( OR=0.35,95% CI:0.17~0.72)、度洛西汀( OR=0.35, 95% CI: 0.17~0.73)、帕罗西汀( OR=0.52,95% CI:0.30~0.88)的不耐受发生率显著高于安慰剂(均 P<0.05),网状meta的累积概率排序为丙咪嗪(95.7%)、舍曲林(69.6%)、文拉法辛(68.6%)、度洛西汀(68.2%)等。结论:在13种抗抑郁药中,度洛西汀、氟西汀、艾司西酞普兰和文拉法辛治疗儿童青少年抑郁症的效果优于安慰剂,但度洛西汀和文拉法辛的耐受性较差。

关键词: 儿童青少年抑郁症抗抑郁药疗效耐受性meta分析    
Abstract:

Objective: To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis. Methods: Databases of PubMed, Cochrane Library, EMBASE, Web of Science, PsycINFO, CBM, CNKI and Wanfang Data were searched for randomized controlled trials (RCT) related to antidepressants in treatment of children and adolescents with depression from inception to December 2021. Quality assessment and data extraction from the included RCTs were performed. Statistical analyses of efficacy and tolerability were conducted with Stata 15.1 software. Surface under the cumulative ranking (SUCAR) was used to rank the value of the antidepressants. Results: A total of 33 RCTs were included in 32 articles, involving 6949 patients. There are 13 antidepressants used in total, including amitriptyline, vilazodone, fluoxetine, selegiline, paroxetine, imipramine, desipramine, sertraline, nortriptyline, escitalopram, citalopram, venlafaxine and duloxetine. The results of network meta-analysis showed that the efficacy of duloxetine ( OR=1.95, 95% CI: 1.41–2.69), fluoxetine ( OR=1.73, 95% CI: 1.40–2.14), venlafaxine ( OR=1.37, 95% CI: 1.04–1.80) and escitalopram ( OR=1.48, 95% CI: 1.12–1.95) were significantly higher than that of placebos (all P<0.05); the probability cumulative ranks were duloxetine (87.0%), amitriptyline (83.3%), fluoxetine (79.0%), escitalopram (62.7%), etc. The results showed that the intolerability of patients receiving imipramine (OR=0.15, 95% CI: 0.08–0.27), sertraline ( OR=0.33, 95% CI: 0.16–0.71), venlafaxine ( OR=0.35, 95% CI: 0.17–0.72), duloxetine ( OR=0.35, 95% CI: 0.17–0.73) and paroxetine ( OR=0.52, 95% CI: 0.30–0.88) were significantly higher than that of placebos (all P<0.05), and the probability cumulative ranks were imipramine (95.7%), sertraline (69.6%), venlafaxine (68.6%), duloxetine (68.2%), etc.Conclusion: Among 13 antidepressants, duloxetine, fluoxetine, escitalopram and venlafaxine are significantly better than placebo in terms of efficacy, but duloxetine and venlafaxine are less well tolerated.

Key words: Children    Adolescents    Depression    Antidepressant    Efficacy    Tolerance    Meta-analysis
收稿日期: 2022-04-14 出版日期: 2022-11-16
CLC:  R749  
基金资助: 国家自然科学基金(81973060)
通讯作者: 杨荣旺     E-mail: ongwang
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引用本文:

饶燕晓,杨荣旺,赵京,曹庆久. 抗抑郁药物治疗儿童青少年抑郁症疗效和耐受性的网状meta分析[J]. 浙江大学学报(医学版), 2022, 51(4): 480-490.

RAO Yanxiao,YANG Rongwang,ZHAO Jing,CAO Qingjiu. Efficacy and tolerability of antidepressant drugs in treatment of depression in children and adolescents: a network meta-analysis. J Zhejiang Univ (Med Sci), 2022, 51(4): 480-490.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0145        https://www.zjujournals.com/med/CN/Y2022/V51/I4/480

  图 1 抗抑郁药物治疗儿童青少年抑郁症相关文献筛选流程图

编号

第一作者 [文献序号]

发表年份

国家

诊断标准

分组及例数(用药剂量)

治疗时间(周)

年龄范围(岁)

女性比例(%)

结局指标

1

Findling [10]

2009

美国

DSM-Ⅳ

氟西汀 =18(10~20?mg/d)安慰剂=16

8

12~17

14.7

有效率

2

March [11]

2004

美国

DSM-Ⅳ

氟西汀 =109(10~40?mg/d)安慰剂=112

12

12~17

54.4

有效率、耐受性

3

Atkinson [12]

2014

美国、俄罗斯、法国、芬兰、德国、乌克兰、爱沙尼亚、斯洛伐克

DSM-Ⅳ-TR

度洛西汀 =117(60~120?mg/d)氟西汀 =117(20~40?mg/d)安慰剂=103

10

7~17

52.2

有效率、耐受性

4

Attari [13]

2006

伊朗

DSM-Ⅳ

去甲替林 =20(2?mg·kg –1·d –1) 氟西汀 =20(1?mg·kg –1·d –1)

8

7~16

50.0

有效率

5

DelBello [14]

2014

美国

DSM-Ⅳ-TR

司来吉兰 =152(6~24?mg/d)安慰剂=156

12

12~17

64.0

有效率、耐受性

6

Kye [15]

1996

美国

K-SADS和RDC

阿米替林 =18(5?mg·kg –1·d –1) 安慰剂=13

8

13~18

29.0

有效率、耐受性

7

Weihs [16]

2018

美国、墨西哥

DSM-Ⅳ-TR

文拉法辛 =115(25~50?mg/d)氟西汀 =112(20?mg/d)安慰剂=112

8

7~18

54.3

有效率、耐受性

8

杜海霞 [17]

2008

中国

CCMD-3

文拉法辛 =32(100~250?mg/d)氟西汀 =33(20~40?mg/d)

6

9~16

60.0

有效率

9

Wagner [28]

2006

美国

DSM-IV

艾司西酞普兰=131(10~20?mg/d)安慰剂=133

8

6~17

51.9

有效率、耐受性

10

Puig-Antich [29]

1987

美国

K-SADS和RDC

丙咪嗪 =20(2~5?mg·kg –1·d –1) 安慰剂=22

5

6~18

36.8

有效率

11

Geller [30]

1992

未提及

DSM-Ⅲ

去甲替林 =26(140?mg/d)安慰剂=24

10

6~12

30.0

有效率

12

Findling [31]

2013

美国

DSM-Ⅳ-TR

艾司西酞普兰=155(10~20?mg/d)安慰剂=157

8

12~17

59.0

有效率、耐受性

13

Emslie [32]

1997

美国

DSM-Ⅲ-R

氟西汀 =48(20?mg/d)安慰剂=48

8

7~17

45.8

有效率、耐受性

14

Wagner [33]

2003

美国、印度、加拿大、哥斯达黎加、墨西哥

DSM-Ⅳ

舍曲林 =189(200?mg/d)安慰剂=187

10

6~17

51.1

有效率、耐受性

15

Rynn [34]

2006

美国、加拿大、哥斯达黎加、墨西哥

DSM-Ⅳ

舍曲林 =100(50~200?mg/d)安慰剂=126

10

6~17

48.0

有效率、耐受性

16

Le Noury [35]

2015

美国、加拿大

DSM-Ⅳ

帕罗西汀 =93(20~40?mg/d)丙咪嗪 =95(200~300?mg/d)安慰剂=87

8

12~18

62.2

有效率、耐受性

17

Keller [36]

2001

美国、加拿大

DSM-Ⅳ

帕罗西汀 =93(20~40?mg/d)丙咪嗪 =95(200~300?mg/d)安慰剂=87

8

12~18

62.2

有效率、耐受性

18

Emslie [37]

2014

美国、加拿大、墨西哥

DSM-Ⅳ-TR

度洛西汀 =224(30~60?mg/d)氟西汀 =117(20?mg/d)安慰剂=122

10

7~17

51.2

有效率、耐受性

19

Berard [38]

2006

英国、加拿大、意大利、墨西哥、西班牙、荷兰、比利时、阿根廷、南非、阿联酋

DSM-Ⅳ

帕罗西汀 =182(20~40?mg/d)安慰剂=93

8

13~18

66.5

有效率、耐受性

20

Durgam [39]

2018

美国

DSM-Ⅳ-TR

维拉唑酮 =355(15~30?mg/d)安慰剂=171

8

12~17

59.5

有效率、耐受性

21

Emslie [40]

2002

美国

DSM-Ⅳ

氟西汀 =109(20?mg/d)安慰剂=110

10

8~18

49.3

有效率、耐受性

22

Emslie [41]

2009

美国

DSM-Ⅳ

艾司西酞普兰=155(10~20?mg/d)安慰剂=157

8

12~17

59.0

有效率、耐受性

23

Wagner [42]

2004

美国

DSM-Ⅳ

西酞普兰=89 (20~40?mg/d)安慰剂=85

8

7~17

53.4

有效率、耐受性

24

张锦绣 [43]

2012

中国

ICD-10

西酞普兰 =36(10~20?mg/d)舍曲林 =38(50~150?mg/d)

6

14~18

55.4

有效率

25

季卫东 [44]

2008

中国

CCMD-3

文拉法辛 =30(150?mg/d)氟西汀 =30(20?mg/d)

8

12~18

46.7

有效率

26

Emslie [45]*

2007

美国

DSM-Ⅳ

文拉法辛 =179(225?mg/d)安慰剂=175

8

7~17

45.5

有效率、耐受性

27

Emslie [46]

2006

美国、加拿大

DSM-Ⅳ

帕罗西汀 =101(10~50?mg/d)安慰剂=102

8

7~17

46.8

有效率、耐受性

28

Findling [47]

2020

美国、加拿大

DSM-Ⅳ-TR

维拉唑酮 =187(15~30?mg/d)氟西汀 =97(20?mg/d)安慰剂=186

8

7~17

60.2

有效率、耐受性

29

万纯 [48]

2006

中国

CCMD-3

西酞普兰 =38(10~30?mg/d)阿米替林 =37(50~150?mg/d)

8

14~18

42.7

有效率

30

闫凤娟 [49]

2014

中国

CCMD-3

西酞普兰 =22(10~20?mg/d)氟西汀 =23(20~40?mg/d)

6

14~18

48.9

有效率

31

Klein [50]

1998

美国

DSM-Ⅲ-R

地昔帕明 =23(50~300?mg/d)安慰剂=22

6

6~17

67.0

有效率、耐受性

32

Atkinson [51]

2018

美国、智利

DSM-Ⅲ-R

文拉法辛 =243(25~50?mg/d)安慰剂=120

8

7~18

56.5

有效率、耐受性

表 1  纳入文献的基本信息
图2  纳入研究偏倚风险分析结果
图3  抗抑郁药物有效率和耐受性证据关系图 A:13种抗抑郁药的有效率证据关系图;B:12种抗抑郁药物的耐受性证据关系图.
图4  抗抑郁药物有效率和耐受性网状meta分析结果 [ (95% )] ORCIAMI:阿米替林;DES:地昔帕明;FLU:氟西汀;PAR:帕罗西汀;IMP:丙咪嗪;SER:舍曲林;ESC:艾司西酞普兰;VEN:文拉法辛;DUL:度洛西汀;SEL:司来吉兰;NOR:去甲替林;CIT:西酞普兰;VIL:维拉唑酮;PBO:安慰剂; 差异有统计学意义.
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