Williams Katrina, Brignell Amanda, Randall Melinda, Silove Natalie, Hazell Philip
Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, 50 Flemington Rd, Parkville, Victoria, Australia, 3052.
Cochrane Database Syst Rev. 2013 Aug 20;2013(8):CD004677. doi: 10.1002/14651858.CD004677.pub3.
Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours.
To determine if treatment with an SSRI:1. improves the core features of autism (social interaction, communication and behavioural problems);2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;3. improves the quality of life of adults or children and their carers;4. has short- and long-term effects on outcome;5. causes harm.
We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field.
Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD.
Two authors independently selected studies for inclusion, extracted data and appraised each study's risk of bias.
Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety.
AUTHORS' CONCLUSIONS: There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.
自闭症谱系障碍(ASD)的特征是社交互动和沟通技能异常,以及刻板行为、活动受限和兴趣狭窄。选择性5-羟色胺再摄取抑制剂(SSRI)被用于治疗常与ASD共病的疾病,如抑郁、焦虑和强迫行为。
确定使用SSRI进行治疗是否:1. 改善自闭症的核心特征(社交互动、沟通和行为问题);2. 改善行为或功能的其他非核心方面,如自伤行为;3. 改善成人或儿童及其照料者的生活质量;4. 对治疗结果有短期和长期影响;5. 造成伤害。
截至2013年3月,我们检索了以下数据库:Cochrane系统评价数据库、Ovid MEDLINE、Embase、护理学与健康领域数据库、心理学文摘数据库、教育资源信息中心数据库和社会学文摘数据库。我们还检索了ClinicalTrials.gov和国际临床试验注册平台(ICTRP)。通过检索参考文献列表和联系该领域知名专家进行补充。
在ASD患者中,比较任何剂量口服SSRI与安慰剂的随机对照试验(RCT)。
两位作者独立选择纳入研究、提取数据并评估每项研究的偏倚风险。
纳入9项RCT,共320名参与者。评估了4种SSRI:氟西汀(3项研究);氟伏沙明(2项研究);芬氟拉明(2项研究);西酞普兰(2项研究)。5项研究仅纳入儿童,4项研究仅纳入成人。参与者的诊断标准和智商的纳入标准各不相同。报告了18种不同的结局指标。尽管不止一项研究报告了临床总体印象(CGI)和强迫行为(OCB)的数据,但每项研究使用了这些结局的不同工具类型或组成部分。因此,除了一个结局(改善比例)外,数据不适合进行Meta分析。一项针对儿童的大型高质量研究未显示西酞普兰有积极作用的证据。三项针对成人的小型研究显示CGI和OCB有积极结果;一项研究显示攻击行为有所改善,另一项研究显示焦虑有所改善。
没有证据表明SSRI对儿童有效,且有新证据表明其有危害。在偏倚风险不明的小型研究中,仅有有限证据表明SSRI对成人有效。