Nanda N.J. Rommelse

BACKGROUND Irritability is a cross-diagnostic trait that affects a significant proportion of adolescents with mental disorders, including those with attention-deficit/hyperactivity disorder (ADHD). It puts serious burden on youth, families, and society while treatment options are limited. The use of micronutrients as food supplements to alleviate mental health issues has steadily increased in Europe over the recent decades, even though their efficacy and tolerability have not been sufficiently investigated. The few randomized controlled trials that investigated broad-spectrum micronutrient supplementation to reduce irritability or ADHD symptoms have reported benefits mostly on global functioning. However, support for an effect on irritability in a cross-diagnostic sample with and without ADHD, including both medicated and unmedicated children and adolescents is currently lacking. OBJECTIVE To investigate the effects of a broad-spectrum micronutrient (vitamins and minerals) supplement on irritability in a total of 210 children and adolescents. METHODS This trial aims to include youths 11−17;6 years old; 50% using any psychotropic medication and 30% females with a high level of irritability with ADHD (67%) or with other mental conditions. The investigational product includes NADH, Folic Acid, Vitamin B6, B12, and D3, Magnesium, Zinc, Iron, Selenium, Phospholipids and L-carnitine (a more restricted selection than many other broad-spectrum formulas). The study consists of a 10-week double blind, placebo-controlled supplement treatment phase, followed by a 10-week open-label treatment phase and concluded by a two-week follow-up. The primary endpoint is week-10 responder status on the Clinical Global Impression Scale of Improvement (CGI-I, irritability) 1–2 and ≥ 30% parent-rated Affective Reactivity Index (ARI) reduction — analyzed via logistic regression adjusted for center, age, sex, diagnostic group (with/without ADHD), medication status, and baseline ARI. A broad range of secondary measures (behavioral, cognitive, biological) is assessed during five study visits at intervals of five weeks. RESULTS The data have been collected between September 2020 and December 2022. The results have not yet been analyzed. CONCLUSIONS This trial is the first to test an irritability-focused responder outcome of micronutrient supplementation in a cross-diagnostic, medicated/unmedicated sample of children and adolescents with/without ADHD. This study will help to evaluate the usefulness of a micronutrient supplement in the treatment of youth with emotional and behavioral problems, whether or not adjunctive to psychotropic medication. CLINICALTRIAL The trial was prospectively registered with ClinicalTrials.gov: NCT03898336, April, 1, 2019