Verbeeck Wim, Bekkering Geertruida E, Van den Noortgate Wim, Kramers Cornelis
Centrum ADHD/ASS, GGZ Vincent van Gogh Instituut Venray, Noordsingel 39, Venray, Netherlands, 5801 GJ.
Cochrane Database Syst Rev. 2017 Oct 2;10(10):CD009504. doi: 10.1002/14651858.CD009504.pub2.
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention, impulsivity and/or excessive activity. The syndrome is commonly accompanied by psychiatric comorbidities and is associated with educational and occupational underachievement.Although psychostimulant medications are the mainstay of treatment for ADHD, not all adults respond optimally to, or can tolerate, these medicines. Thus, alternative non-stimulant treatment approaches for ADHD have been explored. One of these alternatives is bupropion, an aminoketone antidepressant and non-competitive antagonism of nicotinic acetylcholine receptors. Bupropion is registered for the treatment of depression and smoking cessation, but is also used off-label to treat ADHD. OBJECTIVES: To assess the effects and safety of bupropion for the treatment of adults with ADHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and seven other databases in February 2017. We also searched three trials registers and three online theses portals. In addition, we checked references of included studies and contacted study authors to identify potentially relevant studies that were missed by our search. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that evaluated the effects (including adverse effects) of bupropion compared to placebo in adults with ADHD. DATA COLLECTION AND ANALYSIS: Two review authors (WV, GB) independently screened records and extracted data using a data extraction sheet that we tested in a pilot study. We extracted all relevant data on study characteristics and results. We assessed risks of bias using the Cochrane 'Risk of bias' tool, and assessed the overall quality of evidence using the GRADE approach. We used a fixed-effect model to pool the results across studies. MAIN RESULTS: We included six studies with a total of 438 participants. Five studies were conducted in the USA, and one in Iran. All studies evaluated a long-acting version of bupropion, with the dosage ranging from 150 mg up to 450 mg daily. Study intervention length varied from six to 10 weeks. Four studies explicitly excluded participants with psychiatric comorbidity and one study included only participants with opioid dependency. Four studies were funded by industry, but the impact of this on study results is unknown. Two studies were publicly funded and in one of these studies, the lead author was a consultant for several pharmaceutical companies and also received investigator-driven funding from two companies, however none of these companies manufacture bupropion. We judged none of the studies to be free of bias because for most risk of bias domains the study reports failed to provide sufficient details. Using the GRADE approach, we rated the overall quality of evidence as low. We downgraded the quality of the evidence because of serious risk of bias and serious imprecision due to small sample sizes.We found low-quality evidence that bupropion decreased the severity of ADHD symptoms (standardised mean difference -0.50, 95% confidence interval (CI) -0.86 to -0.15, 3 studies, 129 participants), and increased the proportion of participants achieving clinical improvement (risk ratio (RR) 1.50, 95% CI 1.13 to 1.99, 4 studies, 315 participants), and reporting an improvement on the Clinical Global Impression - Improvement scale (RR 1.78, 95% CI 1.27 to 2.50, 5 studies, 337 participants). There was low-quality evidence that the proportion of participants who withdrew due to any adverse effect was similar in the bupropion and placebo groups (RR 1.20, 95% CI 0.35 to 4.10, 3 studies, 253 participants). The results were very similar when using a random-effects model and when we analysed only studies that excluded participants with a psychiatric comorbidity. AUTHORS' CONCLUSIONS: The findings of this review, which compared bupropion to placebo for adult ADHD, indicate a possible benefit of bupropion. We found low-quality evidence that bupropion decreased the severity of ADHD symptoms and moderately increased the proportion of participants achieving a significant clinical improvement in ADHD symptoms. Furthermore, we found low-quality evidence that the tolerability of bupropion is similar to that of placebo. In the pharmacological treatment of adults with ADHD, extended- or sustained-release bupropion may be an alternative to stimulants. The low-quality evidence indicates uncertainty with respect to the pooled effect estimates. Further research is very likely to change these estimates. More research is needed to reach more definite conclusions as well as clarifying the optimal target population for this medicine. Treatment response remains to be reported in a DSM5-diagnosed population. There is also a lack of knowledge on long-term outcomes.
背景:注意力缺陷多动障碍(ADHD)是一种常见的神经生物学疾病,其特征为行为和认知症状,如注意力不集中、冲动和/或活动过度。该综合征常伴有精神共病,并与教育和职业成就低下有关。尽管精神兴奋剂药物是治疗ADHD的主要手段,但并非所有成年人对这些药物都能产生最佳反应或耐受。因此,人们探索了ADHD的替代非兴奋剂治疗方法。其中一种替代方法是安非他酮,一种氨基酮类抗抑郁药,对烟碱型乙酰胆碱受体具有非竞争性拮抗作用。安非他酮已注册用于治疗抑郁症和戒烟,但也被用于治疗ADHD的非适应证用药。 目的:评估安非他酮治疗成人ADHD的疗效和安全性。 检索方法:我们于2017年2月检索了Cochrane对照试验中央登记库(CENTRAL)、MEDLINE、Embase和其他七个数据库。我们还检索了三个试验注册库和三个在线论文门户。此外,我们检查了纳入研究的参考文献,并联系了研究作者,以识别我们检索遗漏的潜在相关研究。 选择标准:我们纳入了所有评估安非他酮与安慰剂相比对成人ADHD疗效(包括不良反应)的随机对照试验(RCT)。 数据收集与分析:两位综述作者(WV,GB)独立筛选记录,并使用我们在一项预试验中测试过的数据提取表提取数据。我们提取了所有关于研究特征和结果的相关数据。我们使用Cochrane“偏倚风险”工具评估偏倚风险,并使用GRADE方法评估证据的总体质量。我们使用固定效应模型汇总各研究的结果。 主要结果:我们纳入了六项研究,共438名参与者。五项研究在美国进行,一项在伊朗进行。所有研究均评估了长效安非他酮,剂量范围为每日150毫克至450毫克。研究干预时长从六周至十周不等。四项研究明确排除了有精神共病的参与者,一项研究仅纳入了有阿片类药物依赖的参与者。四项研究由行业资助,但这对研究结果的影响尚不清楚。两项研究由公共资金资助,其中一项研究的主要作者是几家制药公司的顾问,还从两家公司获得了研究者驱动的资金,然而这些公司均不生产安非他酮。我们认为没有一项研究无偏倚,因为对于大多数偏倚风险领域,研究报告未能提供足够详细的信息。使用GRADE方法,我们将证据的总体质量评为低质量。由于存在严重的偏倚风险和因样本量小导致的严重不精确性,我们对证据质量进行了降级。我们发现低质量证据表明,安非他酮降低了ADHD症状的严重程度(标准化均数差 -0.50,95%置信区间(CI)-0.86至 -0.15,3项研究,129名参与者),并增加了达到临床改善的参与者比例(风险比(RR)1.50,95%CI 1.13至1.99,4项研究,315名参与者),以及在临床总体印象 - 改善量表上报告有改善的比例(RR 1.78,95%CI 1.27至2.50,5项研究,337名参与者)。有低质量证据表明,因任何不良反应而退出的参与者比例在安非他酮组和安慰剂组中相似(RR 1.20,95%CI 0.35至4.10,3项研究,253名参与者)。当使用随机效应模型以及仅分析排除有精神共病参与者的研究时,结果非常相似。 作者结论:本综述将安非他酮与安慰剂用于成人ADHD进行比较,结果表明安非他酮可能有益。我们发现低质量证据表明,安非他酮降低了ADHD症状的严重程度,并适度增加了ADHD症状达到显著临床改善的参与者比例。此外,我们发现低质量证据表明,安非他酮的耐受性与安慰剂相似。在成人ADHD的药物治疗中,缓释或长效安非他酮可能是兴奋剂的一种替代药物。低质量证据表明汇总效应估计存在不确定性。进一步的研究很可能会改变这些估计。需要更多的研究以得出更明确的结论,并阐明该药物的最佳目标人群。治疗反应仍有待在DSM5诊断的人群中报告。关于长期结局也缺乏相关知识。
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