Objective

To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample.

Method

A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory−5 (CASI-5). A priori−defined primary outcomes were Clinical Global Impression−Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores.

Results

Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of −0.31 (95% CI = −0.39, −0.23) in the micronutrient group and a mean change of −0.28 (95% CI = −0.38, −0.19) in the placebo group. However, the between-group difference was not significant (mean change = −0.02; 97.5% CI = −0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred.

Conclusion

Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level.

Clinical trial registration information

Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.

中文翻译：

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微量营养素治疗青少年注意力缺陷/多动症：安慰剂对照随机临床试验

客观的

旨在评估北美儿科样本中微量营养素（维生素/矿物质）是否有益于注意力缺陷/多动障碍 (ADHD) 和烦躁情绪。

方法

在 6 至 12 岁患有 ADHD 且至少有 1 种损害性烦躁症状的 6 至 12 岁未接受药物治疗的儿童中进行了一项 3 中心、为期 8 周、安慰剂对照、随机的微量营养素临床试验，根据家长报告儿童和青少年症状清单−5（ CASI-5）。先验定义的主要结局是临床整体印象改善 (CGI-I)（CGI-I 为 1 或 2 = 治疗有反应者）和家长评定的 ADHD、对立违抗、破坏性情绪失调和同伴的 CASI-5 综合评分冲突症状，包括损伤分数。

结果

在 135 名随机参与者（平均年龄 9.8 岁）中，126 名青少年 (93%) 构成了修改后的意向治疗人群。维持盲法。对于 CGI-I，54% 的微量营养素组和 18% 的安慰剂组有反应（风险比 = 2.97，97.5% CI = 1.50, 5.90，p  < .001）。两组的 CASI-5 综合评分均显着改善 ( p  < .01)，微量营养素组的平均变化为 -0.31 (95% CI = -0.39, -0.23)，平均变化为 -0.28 (95% CI) = -0.38, -0.19) 在安慰剂组中。然而，组间差异并不显着（平均变化 = -0.02；97.5% CI = -0.16, 0.12，效应大小 = 0.07，p  = .70）。微量营养素组比安慰剂组长了 6 毫米 ( p  = .002)。没有发生严重的不良事件或血液和尿液测试相对于基线的临床显着变化。

结论

通过盲法临床医生评级，微量营养素显示出优于安慰剂的总体益处，但根据家长报告的 CASI-5 综合评级，在 ADHD 和易怒人群中，微量营养素并未显示出优于安慰剂的益处。微量营养素显示出更高的身高增长。微量营养素的耐受性良好，大多数参与者都遵守规定的胶囊数量。这项随机对照试验复制了 2 项小型试验中报道的 ADHD 的安全性和有效性，试验的相似配方含有所有维生素和已知的必需矿物质，含量在推荐膳食摄入量和最高可耐受摄入量之间。

临床试验注册信息

青少年多动症微量营养素 (MADDY) 研究；https://clinicaltrials.gov；NCT03252522。