Schachter H M, Pham B, King J, Langford S, Moher D
Thomas C. Chalmers Centre for Systematic Reviews, Children's Hospital of Eastern Ontario Research Institute, Ottawa.
CMAJ. 2001 Nov 27;165(11):1475-88.
Numerous small clinical trials have been carried out to study the behaviourally defined efficacy and safety of short-acting methylphenidate compared with placebo for attention-deficit disorder (ADD) in individuals aged 18 years and less. However, no meta-analyses that carefully examined these questions have been done. We reviewed the behavioural evidence from all the randomized controlled trials that compared methylphenidate and placebo, and completed a meta-analysis.
We searched several electronic sources for articles published between 1981 and 1999: MEDLINE, EMBASE, PsychINFO, ERIC, CINAHL, HEALTHSTAR, Biological Abstracts, Current Contents and Dissertation Abstracts. The Cochrane Library Trials Registry and Current Controlled Trials were also consulted. A study was considered eligible for inclusion if it entailed the following: a placebo-controlled randomized trial that involved short-acting methylphenidate and participants aged 18 years or less at the start of the trial who had received any primary diagnosis of ADD that was made in a systematic and reproducible way.
We included 62 randomized trials that involved a total of 2897 participants with a primary diagnosis of ADD (e.g., with or without hyperactivity). The median age of trial participants was 8.7 years, and the median "percent male" composition of trials was 88.1%. Most studies used a crossover design. Using the scores from 2 separate indices, this collection of trials exhibited low quality. Interventions lasted, on average, 3 weeks, with no trial lasting longer than 28 weeks. Each primary outcome (hyperactivity index) demonstrated a significant effect of methylphenidate (effect size reported by teacher 0.78, 95% confidence interval [CI] 0.64-0.91; effect size reported by parent 0.54, 95% CI 0.40-0.67). However, these apparent beneficial effects are tempered by a strong indication of publication bias and the lack of robustness of the findings, especially those involving core ADD features. Methylphenidate also has an adverse event profile that requires consideration. For example, clinicians only need to treat 4 children to identify an episode of decreased appetite.
Short-acting methylphenidate has a statistically significant clinical effect in the short-term treatment of individuals with a diagnosis of ADD aged 18 years and less. However, the extension of this placebo-controlled effect beyond 4 weeks of treatment has not been demonstrated. Exact knowledge of the extent and definition of the short-term behavioural usefulness of methylphenidate is questioned.
已经开展了许多小型临床试验，以研究与安慰剂相比，速效哌醋甲酯对18岁及以下注意力缺陷障碍（ADD）患者行为学定义的疗效和安全性。然而，尚未进行仔细研究这些问题的荟萃分析。我们回顾了所有比较哌醋甲酯和安慰剂的随机对照试验的行为学证据，并完成了一项荟萃分析。
我们在几个电子资源中搜索了1981年至1999年发表的文章：医学文献数据库（MEDLINE）、荷兰医学文摘数据库（EMBASE）、心理学文摘数据库（PsychINFO）、教育资源信息中心数据库（ERIC）、护理学与健康领域数据库（CINAHL）、健康之星数据库（HEALTHSTAR）、生物学文摘数据库、现刊目次数据库和学位论文文摘数据库。还查阅了考克兰图书馆试验注册库和当前对照试验库。如果一项研究符合以下条件，则被认为有资格纳入：一项安慰剂对照的随机试验，涉及速效哌醋甲酯，且试验开始时年龄在18岁及以下、经系统且可重复诊断为ADD的参与者。
我们纳入了62项随机试验，共2897名初步诊断为ADD（如伴有或不伴有多动）的参与者。试验参与者的年龄中位数为8.7岁，试验中“男性百分比”的中位数为88.1%。大多数研究采用交叉设计。根据两个单独指标的评分，这组试验质量较低。干预平均持续3周，没有试验持续超过28周。每个主要结局（多动指数）都显示哌醋甲酯有显著效果（教师报告的效应量为0.78，95%置信区间[CI]为0.64 - 0.91；家长报告的效应量为0.54，95%CI为0.40 - 0.67）。然而，这些明显的有益效果受到强烈的发表偏倚迹象以及研究结果缺乏稳健性的影响，尤其是那些涉及ADD核心特征的结果。哌醋甲酯的不良事件情况也需要考虑。例如，临床医生仅需治疗4名儿童就能发现1例食欲下降事件。
速效哌醋甲酯在短期治疗18岁及以下诊断为ADD的个体中具有统计学显著的临床效果。然而，这种安慰剂对照效应在治疗4周后的持续情况尚未得到证实。哌醋甲酯短期行为学有效性的程度和定义的确切情况受到质疑。
