Abstract
Objective: Irritability is a transdiagnostic feature common in youth with elevated ADHD and autistic traits. This study examined whether neurodevelopmental profiles influenced treatment response in The BEAM (Balancing Emotions of Adolescents with Micronutrients) study that investigated broad-spectrum micronutrient (vitamins and minerals) efficacy and safety versus placebo for teenagers with moderate-severe irritability symptoms.
Method: We conducted a secondary analysis in a neurodivergent subgroup (n = 97), defined as teens with elevated ADHD and/or autistic traits. Treatment effects of micronutrients were evaluated across clinician-, parent-, and self-reported outcomes.
Results: Between group comparisons favoured micronutrients, although effect size magnitude varied by domain. Clinician-rated ADHD symptoms showed small, non-significant effects (all ds ≤ 0.19). Moderate and significant effects were observed for emotional dysregulation and internalizing symptoms, including dysphoria (d = 0.55, 95%CI: 0.12–0.98) and suicidal ideation (d = 0.54, 95%CI: 0.11–0.98), alongside improvements in stress (d = 0.42), quality of life (d = 0.46), and prosocial behaviour (d = 0.43). Clinician ratings showed moderate effects for global functioning (d = 0.56) and irritability (ds = 0.41–0.49). While there were no significant differences in responder rates in ASD-only or ADHD-only groups, youth with co-occurring ADHD and ASD traits showed significantly higher odds of response based on clinician ratings in the micronutrient group (50%) versus placebo (21.7%) (χ 2 = 3.92, p = .048; OR = 3.60, 95%CI: 0.99-13.16). There were no group differences in side effects.
Conclusions: Micronutrients were associated with improvements in emotional dysregulation, global functioning, and irritability, but not core ADHD symptoms. Treatment effects were most evident in youth with co-occurring ADHD and ASD traits, indicating greater treatment-placebo differentiation in this subgroup.
Clinical trial registration information: BEAM: Balancing Emotions for Adolescents with Micronutrients https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381338