Skip to main content
Springer Nature Link
Log in

Problems most concerning to parents of children with ADHD and emotional dysregulation in a randomized controlled trial of multinutrients: MADDY secondary analysis

  • Original Contribution
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

Abstract

Objective

With dual focus on structured, objective quantification of parent observations of child’s behavior and identifying behaviors most amenable to change, this report examines Parent Target Problems (PTP) as a secondary outcome in a randomized clinical trial (RCT) of children with attention-deficit/ hyperactivity disorder (ADHD) in which one primary outcome, Clinical Global Impression-Improvement, showed a significant advantage of multinutrients over placebo and the other, Likert-type parent ratings, showed significant improvement in both groups, without significant difference between them.

Method

In a multisite 8-week RCT of broad-spectrum micronutrients (“multinutrients”), parents of children ages 6–12 (N = 126, 73% male, 88% white) with ADHD and emotional dysregulation nominated their child’s most concerning problem(s) at baseline and quantified them by frequency, duration, impairment, and consequences. At subsequent visits, parents re-quantified the problem(s). Blinded child psychiatrists independently reviewed the PTPs and rated change at two timepoints compared to baseline. PTPs were grouped into 9 categories. Mean ratings were compared between active and placebo groups and explored by category.

Results

By week 8, a significant separation favored multinutrients: 38% of the multinutrient group were “definitely improved” or better, compared to 25% of the placebo group, and ratings of “no change” or “worse” occurred in 35% with placebo versus 23% with multinutrients (p = 0.04). Inattention (72.2%) and emotional dysregulation (69.1%) were the most frequently reported PTP categories. Inattention and internalizing symptoms improved more with multinutrients than placebo (p = 0.01, d = 0.55; p = 0.03, d = 0.80, respectively). The multinutrient advantage was not significant for 7 other symptoms, including hyperactivity/impulsivity, aggression, autistic symptoms, or emotional dysregulation/irritable oppositionality.

Conclusions

This secondary analysis found that the multinutrients, compared to placebo, were associated with improvements in parental concerns overall, and in two domains specifically: inattention and internalizing symptoms (anxiety/depression), but not in seven domains: hyperactivity/impulsivity, aggression, autistic symptoms or physiological symptoms, peer relationships or emotional dysregulation/irritable oppositionality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
€32.70 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Finland)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rosen PJ, Factor PI (2015) Emotional Impulsivity and Emotional and Behavioral Difficulties Among Children With ADHD: An Ecological Momentary Assessment Study, J. Atten. Disord, vol. 19, no. 9, pp. 779–793, Sep. https://doi.org/10.1177/1087054712463064

  2. Daley D et al (2018) Sep., Practitioner Review: Current best practice in the use of parent training and other behavioural interventions in the treatment of children and adolescents with attention deficit hyperactivity disorder, J. Child Psychol. Psychiatry, vol. 59, no. 9, pp. 932–947, https://doi.org/10.1111/jcpp.12825

  3. Sonuga-Barke EJ et al (2013) Mar., Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments, Am. J. Psychiatry, vol. 170, no. 3, pp. 275–289, https://doi.org/10.1176/APPI.AJP.2012.12070991

  4. Johnstone JM et al (2022) Micronutrients for Attention-Deficit/Hyperactivity disorder in youths: a placebo-controlled Randomized Clinical Trial. J Am Acad Child Adolesc Psychiatry. https://doi.org/10.1016/J.JAAC.2021.07.005

    Article  PubMed  Google Scholar 

  5. Rucklidge JJ, Eggleston MJF, Johnstone JM, Darling K, Frampton CM (2018) Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial, J. Child Psychol. Psychiatry, vol. 59, no. 3, pp. 232–246, Mar. https://doi.org/10.1111/jcpp.12817

  6. Guy W ECDEU assessment manual for psychopharmacology, Revised. National Institute of Mental Health, Psychopharmacology Research Branch, 1976. [Online]. Available: https://openlibrary.org/books/OL24341821M/ECDEU_assessment_manual_for_psychopharmacology

  7. Guy W (2000) Clinical global impressions (CGI) scale., in Handbook of Psychiatric Measures, 1st ed., Washington, D.C.: American Psychiatric Association, pp. 100–102. Accessed: Oct. 19, 2023. [Online]. Available: https://doi.org/10.1176/appi.ps.53.5.639

  8. Piasecki TM, Hufford MR, Solhan M, Trull TJ (2007) Assessing clients in their natural environments with electronic diaries: Rationale, benefits, limitations, and barriers. Psychol Assess 19(1):25–43. https://doi.org/10.1037/1040-3590.19.1.25

    Article  PubMed  Google Scholar 

  9. Clark DL et al (2008) Mar., Vestibular Stimulation for ADHD: randomized controlled trial of Comprehensive Motion Apparatus, J. Atten. Disord, vol. 11, no. 5, pp. 599–611, https://doi.org/10.1177/1087054707311042

  10. Panagiotakos D (2009) Health Measurement Scales: Methodological Issues, Open Cardiovasc. Med. J, vol. 3, pp. 160–165, Nov. https://doi.org/10.2174/1874192400903010160

  11. American Psychiatric Association (2013) DSM-V: Diagnostic and Statistical Manual of Mental disorders. Fifth Am Psychiatric Association. https://doi.org/10.1176/appi.books.9780890425596

    Article  Google Scholar 

  12. Mulligan A et al (2013) Home environment: association with hyperactivity/impulsivity in children with ADHD and their non-ADHD siblings. Child Care Health Dev 39(2):202–212. https://doi.org/10.1111/j.1365-2214.2011.01345.x

    Article  CAS  PubMed  Google Scholar 

  13. Arnold LE, Wender PH, McCloskey K, Snyder SH (1972) Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms, Arch. Gen. Psychiatry, vol. 27, no. 6, pp. 816–822, Dec. https://doi.org/10.1001/archpsyc.1972.01750300078015

  14. Arnold LE et al (2003) Dec., Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials, J. Am. Acad. Child Adolesc. Psychiatry, vol. 42, no. 12, pp. 1443–1450, https://doi.org/10.1097/00004583-200312000-00011

  15. McGuire JF et al (2014) Dec., Individualized Assessments in Treatment Research: An Examination of Parent-Nominated Target Problems in the Treatment of Disruptive Behaviors in Youth with Tourette Syndrome, Child Psychiatry Hum. Dev, vol. 45, no. 6, pp. 686–694, https://doi.org/10.1007/s10578-014-0437-7

  16. Scahill L et al (2017) Mar., Using a Patient-Centered Outcome Measure to Test Methylphenidate Versus Placebo in Children with Autism Spectrum Disorder, J. Child Adolesc. Psychopharmacol, vol. 27, no. 2, pp. 125–131, https://doi.org/10.1089/cap.2016.0107

  17. Sheridan E et al (2021) Jul., Using Parent Target Problem Narratives to Evaluate Outcomes in Children with Autism Spectrum Disorder, Res. Child Adolesc. Psychopathol, vol. 49, pp. 1527–1535

  18. Weisz JR et al (2011) Jun., Youth Top Problems: using idiographic, consumer-guided assessment to identify treatment needs and to track change during psychotherapy, J. Consult. Clin. Psychol, vol. 79, no. 3, pp. 369–380, https://doi.org/10.1037/a0023307

  19. Johnstone JM et al (2019) Rationale and design of an international randomized placebo-controlled trial of a 36-ingredient micronutrient supplement for children with ADHD and irritable mood: the micronutrients for ADHD in Youth (MADDY) study. Contemp Clin Trials Commun. https://doi.org/10.1016/j.conctc.2019.100478

    Article  PubMed  PubMed Central  Google Scholar 

  20. Johnstone JM et al (2023) Dr. Johnstone Aug. Reply to Dr. Elmrayed, J. Am. Acad. Child Adolesc. Psychiatry, pp. S0890-8567(23)01423–5, https://doi.org/10.1016/j.jaac.2023.07.994

  21. Institute of Medicine (1998) Dietary reference intakes for Thiamin, Riboflavin, Niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and Choline. National Academies, Washington, DC

    Google Scholar 

  22. Institute of Medicine (2001) Dietary reference intakes for vitamin. In: Vitamin A, Arsenic K (eds) Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. The National Academies, Washington, DC

    Google Scholar 

  23. Institute of Medicine (2011) Dietary reference intakes for calcium and Vitamin D. The National Academies., Washington, DC

    Google Scholar 

  24. Leibenluft E (Apr. 2017) Pediatric Irritability: A systems Neuroscience Approach. Trends Cogn Sci 21(4):277–289. https://doi.org/10.1016/j.tics.2017.02.002

  25. Leibenluft E, Stoddard J (2013) The developmental psychopathology of irritability, Dev. Psychopathol, vol. 25, no. 4 Pt 2, pp. 1473–1487, Nov. https://doi.org/10.1017/S0954579413000722

  26. International statistical classification of diseases and related health problems. (2019) Accessed: Oct. 19, 2023. [Online]. Available: https://icd.who.int/

  27. StataCorp (2017) Stata Statistical Software. StataCorp LLC, College Station, TX

  28. Rucklidge JJ, Johnstone JM, Kaplan BJ (2021) Nutrition Provides the Essential Foundation for Optimizing Mental Health, Evid.-Based Pract. Child Adolesc. Ment. Health, vol. 6, no. 1, pp. 131–154, Jan. https://doi.org/10.1080/23794925.2021.1875342

  29. Kaplan BJ, Crawford SG, Gardner B, Farrelly G (2002) Treatment of mood lability and explosive rage with minerals and vitamins: two case studies in children. J Child Adolesc Psychopharmacol 12(3):205–219. https://doi.org/10.1089/104454602760386897

    Article  PubMed  Google Scholar 

  30. Kaplan BJ, Simpson JS, Ferre RC, Gorman CP, McMullen DM, Crawford SG (2001) Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder, J. Clin. Psychiatry, vol. 62, no. 12, pp. 936–944, Dec. https://doi.org/10.4088/jcp.v62n1204

  31. Rucklidge J, Taylor M, Whitehead K (Jan. 2011) Effect of micronutrients on behavior and mood in adults with ADHD: evidence from an 8-week open label trial with natural extension. J Atten Disord 15(1):79–91. https://doi.org/10.1177/1087054709356173

  32. Gadow KD et al (Jun. 2016) Severely aggressive children receiving stimulant medication Versus Stimulant and Risperidone: 12-Month Follow-Up of the TOSCA Trial. J Am Acad Child Adolesc Psychiatry 55(6):469–478. https://doi.org/10.1016/j.jaac.2016.03.014

  33. Arnold LE, Kirilcuk V, Corson SA, Corson EO (Feb. 1973) Levoamphetamine and dextroamphetamine: differential effect on aggression and hyperkinesis in children and dogs. Am J Psychiatry 130(2):165–170. https://doi.org/10.1176/ajp.130.2.165

  34. Visser L, Röschinger J, Barck K, Büttner G, Hasselhorn M (2022) Learning difficulties in children with symptoms of DCD and/or ADHD: analyses from a categorical and a continuous Approach. Int J Disabil Dev Educ 69(5):1505–1521. https://doi.org/10.1080/1034912X.2020.1786023

    Article  Google Scholar 

  35. Faraone SV, Larsson H (Apr. 2019) Genetics of attention deficit hyperactivity disorder. Mol Psychiatry 24(4):562–562. https://doi.org/10.1038/S41380-018-0070-0

  36. Hatsu IE, Eiterman L, Stern M, Lu S, Johnstone JM, Leung BM, Srikanth P, Robinette L, Tost G, Odei JB, Gracious BL (2022) Household food insecurity is associated with symptoms of emotional dysregulation in children with attention deficit hyperactivity disorder: the MADDY study. Nutrients 14(6):1306

    Article  PubMed  PubMed Central  Google Scholar 

  37. Robinette LM, Hatsu IE, Johnstone JM, Bruton AM, Leung BM, Arnold LE (2023) Treatment response to supplemental nutrients for ADHD is independent of diet quality: the MADDY Study RCT. Nutritional Neuroscience, pp.1–10

  38. Elmrayed S (2023) Dosages of Nutrient Supplements and Potential Long-Term Toxicity in Attention-Deficit/Hyperactivity Disorder Micronutrient Study, J. Am. Acad. Child Adolesc. Psychiatry, Aug. https://doi.org/10.1016/j.jaac.2023.01.027

  39. Leung BMY et al (2023) Jun., Micronutrients for ADHD in youth (MADDY) study: comparison of results from RCT and open label extension, Eur. Child Adolesc. Psychiatry, https://doi.org/10.1007/s00787-023-02236-2

  40. Rucklidge JJ, Eggleston MJF, Ealam B, Beaglehole B, Mulder RT (2019) An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms, J. Altern. Complement. Med, vol. 25, no. 6, pp. 613–622, Jun. https://doi.org/10.1089/acm.2018.0352

  41. Simpson JSA, Crawford SG, Goldstein ET, Field C, Burgess E, Kaplan BJ (2011) Systematic review of safety and tolerability of a complex micronutrient formula used in mental health, BMC Psychiatry, vol. 11, no. 1, p. 62, Apr. https://doi.org/10.1186/1471-244X-11-62

  42. About PCORI Patient-Centered Outcomes Research Institute. Accessed: Oct. 19, 2023. [Online]. Available: https://www.pcori.org/about/about-pcori

  43. Ginsburg GS, McCarthy JJ (2001) Personalized medicine: revolutionizing drug discovery and patient care, Trends Biotechnol, vol. 19, no. 12, pp. 491–496, Dec. https://doi.org/10.1016/s0167-7799(01)01814-5

  44. Hamburg M, Collins F (2010) The path to personalized medicine, N Engl J Med, vol. 363, no. 4, pp. 301–304, Jul. https://doi.org/10.1056/NEJMp1006304

Download references

Acknowledgements

Thank you to the parents and children who participated in the study. The study was supported 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) K2390281846 and T32AT002688 to Oregon Health & Science University (OHSU) and NIH-NCCIH 5R90AT00892403 to the National University for Natural Medicine; 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. The authors report no competing interests to share although Dr. Arnold has received research funding from Supernus Pharmaceuticals, Roche/Genentech Pharmaceuticals, Otsuka Pharmaceuticals, Axial, Yamo Pharmaceuticals, MapLight Therapeutics, Myndlift, Young Living Essential Oils and National Institute of Health (USA, R01 MH 100144), has consulted with Pfizer Pharmaceuticals, Yamo, and CHADD, and been on advisory boards for Otsuka and Roche/Genentech. Supplement and matched placebo were provided by Hardy Nutritionals, who had no input into design, data collection, data analysis, interpretation, or reporting.

Study data may be made available on request by contacting the corresponding author.

Correspondence to:

Jeanette Johnstone, PhD, MA.

Assistant Professor, Oregon Health & Science University.

3181 SW Sam Jackson Park Road, DC7P.

Portland, OR 97239.

(503) 494–3700.

jojeanet@ohsu.edu.

Author information

Authors and Affiliations

  1. Center for Mental Health Innovation, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, DC7P, Portland, Oregon, 97239, United States

    Gabriella Tost, Alisha Bruton, Irene E. Hatsu & Hayleigh K. Ast

  2. National University of Natural Medicine, Helfgott Research Institute, Portland, Oregon, United States

    Jeanette M. Johnstone

  3. OHSU-Portland State University School of Public Health, Portland, Oregon, United States

    Priya Srikanth

  4. The Ohio State University, Columbus, Ohio, United States

    Irene E. Hatsu, Leanna P. Eiterman, Lisa M. Robinette, Craig Williams, Barbara Gracious &  L. Eugene Arnold

  5. Orange Park Medical Center, Florida, Florida, United States

    Barbara Gracious

  6. Edward Via College of Osteopathic Medicine, Auburn, Alabama, United States

    Barbara Gracious

  7. University of Lethbridge, Alberta, Canada

    Brenda MY Leung

Authors
  1. Gabriella Tost
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Priya Srikanth
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Alisha Bruton
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Irene E. Hatsu
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Brenda MY Leung
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Hayleigh K. Ast
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Leanna P. Eiterman
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Lisa M. Robinette
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Craig Williams
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Barbara Gracious
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. L. Eugene Arnold
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Jeanette M. Johnstone
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Ms. Tost, along with Drs. Johnstone and Arnold, wrote the preliminary manuscript draft. All authors contributed to editing. Drs. Arnold, Williams and Gracious rated the PTPs. Dr. Srikanth conducted all analyses and prepared the tables and figures.

Corresponding author

Correspondence to Jeanette M. Johnstone.

Ethics declarations

Competing interests

The authors declare no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tost, G., Srikanth, P., Bruton, A. et al. Problems most concerning to parents of children with ADHD and emotional dysregulation in a randomized controlled trial of multinutrients: MADDY secondary analysis. Eur Child Adolesc Psychiatry 33, 4335–4347 (2024). https://doi.org/10.1007/s00787-024-02463-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-024-02463-1

Keywords