Gillies Donna, Sinn John Kh, Lad Sagar S, Leach Matthew J, Ross Melissa J
Western Sydney and Nepean Blue Mountains Mental Health Service, Parramatta, Australia.
Cochrane Database Syst Rev. 2012 Jul 11;2012(7):CD007986. doi: 10.1002/14651858.CD007986.pub2.
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity and impulsivity, and is associated with long-term social, academic and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Children and adolescents with ADHD have been shown to have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD.
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
We searched the following databases in August 2011: CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (1948 to July Week 3, 2011), EMBASE (1980 to 2011 Week 29), PsycINFO (1806 to current), CINAHL (1937 to current), BIOSIS (1969 to 30 July 2011), Science Citation Index (1970 to 30 July 2011), Social Science Citation Index (1970 to 30 July 2011), Conference Proceedings Citation Index - Science (1990 to 30 July 2011), Conference Proceedings Citation Index - Social Science and Humanities (1990 to 30 July 2011), Cochrane Database of Systematic Reviews (2011, Issue 7), DARE (2011 Issue 2), Dissertation Abstracts (via Dissertation Express) and the metaRegister of Controlled Trials (mRCT). In addition, we searched the following repositories for theses on 2 August 2011: DART, NTLTD and TROVE. We also checked reference lists of relevant studies and reviews for additional references.
Two review authors independently assessed the results of the database searches. We resolved any disagreements regarding the selection of studies through consensus or, if necessary, by consultation with a third member of the review team.
Two members of the review team independently extracted details of participants and setting, interventions, methodology and outcome data. If differences were identified, we resolved them by consensus or referral to a third member of the team. We made all reasonable attempts to contact the authors where further clarification or missing data were needed.
We included 13 trials with 1011 participants in the review. After screening 366 references, we considered 23 relevant and obtained the full text for consideration. We excluded five papers and included 18 papers describing the 13 trials. Eight of the included trials had a parallel design: five compared an omega-3 PUFA supplement to placebo; two compared a combined omega-3 and omega-6 supplement to placebo, and one compared an omega-3 PUFA to a dietary supplement. Five of the included trials had a cross-over design: two compared combined omega-3/6 PUFA to placebo; two compared omega-6 PUFA with placebo; one compared omega-3 to omega-6 PUFA, and one compared omega-6 PUFA to dexamphetamine. Supplements were given for a period of between four and 16 weeks.There was a significantly higher likelihood of improvement in the group receiving omega-3/6 PUFA compared to placebo (two trials, 97 participants; risk ratio (RR) 2.19, 95% confidence interval (CI) 1.04 to 4.62). However, there were no statistically significant differences in parent-rated ADHD symptoms (five trials, 413 participants; standardised mean difference (SMD) -0.17, 95% CI -0.38 to 0.03); inattention (six trials, 469 participants; SMD -0.04, 95% CI -0.29 to 0.21) or hyperactivity/impulsivity (five trials, 416 participants; SMD -0.04, 95% CI -0.25 to 0.16) when all participants receiving PUFA supplements were compared to those receiving placebo.There were no statistically significant differences in teacher ratings of overall ADHD symptoms (four trials, 324 participants; SMD 0.05, 95% CI -0.18 to 0.27); inattention (three trials, 260 participants; SMD 0.26, 95% CI -0.22 to 0.74) or hyperactivity/impulsivity (three trials, 259 participants; SMD 0.10, 95% CI -0.16 to 0.35).There were also no differences between groups in behaviour, side effects or loss to follow-up.Overall, there were no other differences between groups for any other comparison.
AUTHORS' CONCLUSIONS: Overall, there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents. The majority of data showed no benefit of PUFA supplementation, although there were some limited data that did show an improvement with combined omega-3 and omega-6 supplementation.It is important that future research addresses current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, short follow-up times and other methodological weaknesses.
注意力缺陷多动障碍（ADHD）是儿童和青少年中的一个主要问题，其特征为注意力不集中、多动和冲动的程度与年龄不符，并伴有长期的社会、学业和心理健康问题。兴奋剂药物哌甲酯和苯丙胺是治疗ADHD最常用的药物，但这些药物并非总是有效，且可能伴有副作用。临床和生化证据表明，多不饱和脂肪酸（PUFA）缺乏可能与ADHD有关。研究表明，患有ADHD的儿童和青少年血浆和血液中的PUFA浓度显著较低，尤其是ω-3多不饱和脂肪酸水平较低。这些发现表明，补充PUFA可能会减少与ADHD相关的注意力和行为问题。
比较PUFA与其他治疗形式或安慰剂在治疗儿童和青少年ADHD症状方面的疗效。
我们于2011年8月检索了以下数据库：CENTRAL（考克兰系统评价数据库2011年第2期）、MEDLINE（1948年至2011年第3周）、EMBASE（1980年至2011年第29周）、PsycINFO（1806年至今）、CINAHL（1937年至今）、BIOSIS（1969年至2011年7月30日）、科学引文索引（1970年至2011年7月30日）、社会科学引文索引（1970年至2011年7月30日）、会议论文引文索引 - 科学（1990年至2011年7月30日）、会议论文引文索引 - 社会科学与人文科学（1990年至2011年7月30日）、考克兰系统评价数据库（2011年第7期）、DARE（2011年第2期）、学位论文摘要（通过学位论文快递）和对照试验元注册库（mRCT）。此外，我们于2011年8月2日在以下论文库中检索了论文：DART、NTLTD和TROVE。我们还检查了相关研究和综述的参考文献列表以获取其他参考文献。
两位综述作者独立评估数据库检索结果。我们通过协商解决了关于研究选择的任何分歧，如有必要，还咨询了综述团队的第三位成员。
综述团队的两名成员独立提取了参与者和研究背景、干预措施、方法和结局数据的详细信息。如果发现差异，我们通过协商或转交给团队的第三位成员来解决。在需要进一步澄清或缺少数据时，我们尽一切合理努力联系作者。
我们纳入了13项试验，共1011名参与者。在筛选了366篇参考文献后，我们认为其中23篇相关，并获取了全文以供考虑。我们排除了5篇论文，纳入了描述13项试验的18篇论文。纳入的试验中有8项采用平行设计：5项将ω-3多不饱和脂肪酸补充剂与安慰剂进行比较；2项将ω-3和ω-6联合补充剂与安慰剂进行比较，1项将ω-3多不饱和脂肪酸与膳食补充剂进行比较。纳入的试验中有5项采用交叉设计：2项将ω-3/6多不饱和脂肪酸联合补充剂与安慰剂进行比较；2项将ω-6多不饱和脂肪酸与安慰剂进行比较；1项将ω-3与ω-6多不饱和脂肪酸进行比较，1项将ω-6多不饱和脂肪酸与右旋苯丙胺进行比较。补充剂服用时间为4至16周。与安慰剂相比，接受ω-3/6多不饱和脂肪酸补充剂的组改善的可能性显著更高（两项试验，97名参与者；风险比（RR）2.19，95%置信区间（CI）1.04至4.62）。然而，当将所有接受多不饱和脂肪酸补充剂的参与者与接受安慰剂的参与者进行比较时，在家长评定的ADHD症状（五项试验，413名参与者；标准化均数差（SMD）-0.17，95%CI -0.38至0.03）、注意力不集中（六项试验469名参与者；SMD -0.04，95%CI -0.29至0.21）或多动/冲动（五项试验，416名参与者；SMD -0.04，95%CI -0.25至0.16）方面无统计学显著差异。在教师评定的总体ADHD症状（四项试验，324名参与者；SMD 0.05，95%CI -0.18至0.27）、注意力不集中（三项试验，260名参与者；SMD 0.26，95%CI -0.22至0.74）或多动/冲动（三项试验，259名参与者；SMD 0.10，95%CI -0.16至0.35）方面也无统计学显著差异。在行为、副作用或失访方面，各组之间也没有差异。总体而言，在任何其他比较中，各组之间没有其他差异。
总体而言，几乎没有证据表明补充多不饱和脂肪酸对儿童和青少年的ADHD症状有任何益处。大多数数据显示补充多不饱和脂肪酸没有益处，尽管有一些有限的数据确实表明ω-3和ω-6联合补充有改善作用。未来的研究解决该领域当前的弱点很重要，这些弱点包括样本量小、选择标准的变异性、补充剂类型和剂量的变异性、随访时间短以及其他方法学弱点。
