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Micronutrients for ADHD in youth (MADDY) study: comparison of results from RCT and open label extension

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Abstract

Background

The Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youth (MADDY) study evaluated the efficacy and safety of a multinutrient formula for children with ADHD and emotional dysregulation. The post-RCT open-label extension (OLE) compared the effect of treatment duration (8 weeks vs 16 weeks) on ADHD symptoms, height velocity, and adverse events (AEs).

Methods

Children aged 6–12 years randomized to multinutrients vs. placebo for 8 weeks (RCT), received an 8–week OLE for a total of 16 weeks. Assessments included the Clinical Global Impression-Improvement (CGI-I), Child and Adolescent Symptom Inventory-5 (CASI-5), Pediatric Adverse Events Rating Scale (PAERS), and anthropometric measures (height and weight).

Results

Of the 126 in the RCT, 103 (81%) continued in the OLE. For those initially assigned to placebo, CGI-I responders increased from 23% in the RCT to 64% in the OLE; those who took multinutrients for 16 weeks increased from 53% (RCT) to 66% responders (OLE). Both groups improved on the CASI-5 composite score and subscales from week 8 to week 16 (all p–values < 0.01). The group taking 16 weeks of multinutrients had marginally greater height growth (2.3 cm) than those with 8 weeks (1.8 cm) (p = 0.07). No difference in AEs between groups was found.

Conclusion

The response rate to multinutrients by blinded clinician ratings at 8 weeks was maintained to 16 weeks; the response rate in the group initially assigned to placebo improved significantly with 8 weeks of multinutrients and almost caught up with 16 weeks. Longer time on multinutrients did not result in greater AEs, confirming an acceptable safety profile.

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Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity; inquiries may be made to the corresponding author.

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Acknowledgements

The MADDY study researchers would like to thank all the parents and children who participated in the study, giving of their time and data to make this study possible.

Funding

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. Financial support from the National Institutes of Health (NIH) National Center for Complementary and Integrative Health (NCCIH) R90AT008924 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; UL1TR002733 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. 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. Micronutrient supplement and matched placebo were donated by Hardy Nutritionals. The study funders/donors had no role in the design, analysis, or reporting of the study.

Author information

Authors and Affiliations

  1. Faculty of Health Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada

    Brenda M. Y. Leung

  2. Oregon Health & Science University-Portland State University School of Public Health, Portland, OR, USA

    Priya Srikanth

  3. Department of Human Sciences, The Ohio State University, Columbus, OH, USA

    Lisa Robinette & Irene Hatsu

  4. Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA

    Alisha M. Bruton, Gabriella Tost & Jeanette M. Johnstone

  5. Department of Psychiatry & Behavioral Health, The Ohio State University, Columbus, OH, USA

    L. Eugene Arnold

  6. Helfgott Research Institute, National University of Natural Medicine, Portland, OR, USA

    Jeanette M. Johnstone

Authors
  1. Brenda M. Y. Leung
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  2. Priya Srikanth
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  3. Lisa Robinette
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  4. Alisha M. Bruton
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  6. Irene Hatsu
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  7. L. Eugene Arnold
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  8. Jeanette M. Johnstone
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Contributions

BMYL wrote and edited the main manuscript text with LEA and JMJ providing additions to the manuscript text. PS conducted all data analyses and prepared the tables and Figs. 2, 3. LR prepared Fig. 1. All authors reviewed the manuscript.

Corresponding author

Correspondence to Brenda M. Y. Leung.

Ethics declarations

Conflict of interest

Dr. Arnold has received research funding from Forest, Lilly, Noven, Shire, Supernus, Roche, and YoungLiving (as well as NIH and Autism Speaks); has consulted with Pfizer, Tris Pharma, and Waypoint; and been on advisory boards for Arbor, Ironshore, Otsuka, Pfizer, Roche, Seaside Therapeutics, Shire. The other authors declare that they have no competing interests.

Ethics approval

The MADDY study was approved by the US Food & Drug Administration under investigational new drug (IND) #127832, Health Canada (Control #207742), the University of Calgary Conjoint Health Research Ethics Board (CHREB) REB #17-0325, Institutional Review Boards at OHSU IRB #16870, and OSU IRB # 2017H0188.

Consent to participate

All participants provided written parental consent and child assent prior to participation.

Consent for publication

All authors consent to the publication of this manuscript.

Availability of data and material

Not applicable.

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Not applicable.

Supplementary Information

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Supplementary file1 (DOCX 16 KB)

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Leung, B.M.Y., Srikanth, P., Robinette, L. et al. Micronutrients for ADHD in youth (MADDY) study: comparison of results from RCT and open label extension. Eur Child Adolesc Psychiatry (2023). https://doi.org/10.1007/s00787-023-02236-2

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