Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial - 25/04/22
, Irene Hatsu, PhD, RD c, Gabriella Tost, BA a, Priya Srikanth, MPH d, Leanna P. Eiterman, PhD c, Alisha M. Bruton, ND, MS a, Hayleigh K. Ast, ND a, Lisa M. Robinette, MS c, Madeline M. Stern, MS c, Elizabeth G. Millington, MC e, Barbara L. Gracious, MD c, f, Andrew J. Hughes, MD a, Brenda M.Y. Leung, PhD e, L. Eugene Arnold, MD, MEd cAbstract |
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; clinicaltrials.gov; NCT03252522.
Le texte complet de cet article est disponible en PDF.Key words : attention-deficit/hyperactivity disorder, irritability, dysregulated mood, micronutrients
Plan
| The study was funded through private donations to the Nutrition and Mental Health Research Fund, managed by the Foundation for Excellence in Mental Health Care (FEMHC), plus a direct grant from FEMHC, and from the Gratis Foundation. Authors also received support from the National Institutes of Health (NIH) National Center for Complementary and Integrative Health (NCCIH) 5R90AT00892403 to the National University for Natural Medicine, NIH-NCCIH T32 AT002688 to Oregon Health & Science University (OHSU); the National Center for Advancing Translational Sciences of the NIH, UL1TR000128, UL1TR002369; 8UL1TR000090-05 at OHSU and Ohio State University; OHSU’s Department of Child and Adolescent Psychiatry; the Department of Behavioral Health and Psychiatry and the Research Institute at Nationwide Children’s Hospital, the Department of Psychiatry and Behavioral Health as well as the Department of Human Sciences at Ohio State University. Dr. Gracious received support from the Jeffrey Fellowship. In Canada, funding was received through the Nutrition and Mental Health Fund, administered by the Calgary Foundation. Dr. Leung is supported by the Emmy Droog Chair in Complementary and Alternative Healthcare. The study funders had no role in the design or reporting of the study. |
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| The research was performed with permission from the Oregon Health & Science University (OHSU; #16870) and the Ohio State University (OSU; #2017H0188) Institutional Review Boards and the Conjoint Health Research Ethics Board at the University of Calgary. |
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| Ms. Srikanth served as the statistical expert for this research. |
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| Author Contributions Conceptualization: Johnstone, Hatsu, Tost, Eiterman, Gracious, Hughes, Leung, Arnold Data curation: Johnstone, Srikanth, Gracious, Leung, Arnold Formal analysis: Johnstone, Srikanth, Robinette Funding acquisition: Johnstone, Hatsu, Gracious, Leung Investigation: Johnstone, Hatsu, Tost, Eiterman, Bruton, Ast, Robinette, Stern, Millington, Gracious, Hughes, Leung, Arnold Methodology: Johnstone, Hatsu, Tost, Srikanth, Ast, Gracious, Leung Project administration: Johnstone, Eiterman, Bruton, Arnold Resources: Johnstone, Leung, Arnold Software: Tost, Gracious, Hughes Supervision: Johnstone, Hatsu, Tost, Eiterman, Gracious, Leung, Arnold Validation: Gracious, Arnold Visualization: Johnstone, Bruton, Arnold Writing – original draft: Johnstone, Tost, Bruton, Robinette, Arnold Writing – review and editing: Johnstone, Hatsu, Tost, Eiterman, Bruton, Ast, Robinette, Stern, Millington, Gracious, Hughes, Leung, Arnold |
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| Disclosure: Dr. Gracious has been or is a consultant to AstraZeneca, Otsuka, and Novo Nordisk. Dr. Arnold has received research funding from Forest, Eli Lilly and Co., Noven, Shire (a Takeda company), Supernus, Roche, YoungLiving, NIH, and Autism Speaks; has consulted with Pfizer, Tris Pharma, and Waypoint; and has been on advisory boards for Arbor, Ironshore, Otsuka, Pfizer, Roche, Seaside Therapeutics, and Shire. Drs. Johnstone, Hatsu, Eiterman, Bruton, Ast, Hughes, Leung and Mss. Tost, Srikanth, Robinette, Stern, Millington have reported no biomedical financial interests or potential conflicts of interest. |
Vol 61 - N° 5
P. 647-661 - mai 2022 Retour au numéro
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