TY - JOUR
T1 - Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths
T2 - A Placebo-Controlled Randomized Clinical Trial
AU - Johnstone, Jeanette M.
AU - Hatsu, Irene
AU - Tost, Gabriella
AU - Srikanth, Priya
AU - Eiterman, Leanna P.
AU - Bruton, Alisha M.
AU - Ast, Hayleigh K.
AU - Robinette, Lisa M.
AU - Stern, Madeline M.
AU - Millington, Elizabeth G.
AU - Gracious, Barbara L.
AU - Hughes, Andrew J.
AU - Leung, Brenda M.Y.
AU - Arnold, L. Eugene
N1 - Funding Information:
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.
Funding Information:
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.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. 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
Publisher Copyright:
© 2021 American Academy of Child and Adolescent Psychiatry
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - attention-deficit/hyperactivity disorder
KW - dysregulated mood
KW - irritability
KW - micronutrients
UR - http://www.scopus.com/inward/record.url?scp=85113577340&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113577340&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2021.07.005
DO - 10.1016/j.jaac.2021.07.005
M3 - Article
C2 - 34303786
AN - SCOPUS:85113577340
SN - 0890-8567
VL - 61
SP - 647
EP - 661
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
IS - 5
ER -