Efficacy and Safety of Micronutrient Treatment for Irritability in Adolescents: 8-Week Double-Blinded Randomized Placebo-Controlled Trial (BEAM)

OBJECTIVE: Irritability is a transdiagnostic dimension characterized by affective and behavioral components. The Balancing Emotions of Adolescents with Micronutrients (BEAM) study investigated broad-spectrum micronutrient (vitamins and minerals) efficacy and safety for adolescents with moderate-to-severe irritability symptoms. METHOD: A total of 132 unmedicated adolescents (12-17 years of age) were randomized to micronutrients (n = 67) or active placebo (n = 65) for 8 weeks and monitored remotely with weekly parent/adolescent questionnaires and monthly online meetings with a registered psychologist. Primary outcome measures were the Clinical Global Impression-Improvement (CGI-I), Emotion Dysregulation Inventory (EDI)-Reactivity subscale, and Clinician Affective Reactivity Index (CL-ARI-Total). RESULTS: Both groups were well matched at baseline. Generalized linear mixed-effect regression models showed significant main effects of treatment on the CGI-I (p = .012), EDI (p = .043), but not CL-ARI-Total (p = .276), although the rate of change over time did not significantly differ between treatment groups. Post hoc analyses showed disruptive mood dysregulation disorder (DMDD) and socio-economic status (SES) modified treatment response; those with DMDD and from lower SES families were more likely to respond to micronutrients. For the entire sample, baseline to end-of-RCT between-group effect sizes (ES) were small-to-medium (0.30-0.36) whereas for those with DMDD (n=30), ES were very large (1.06-1.44); 64.3% of DMDD participants were responders on micronutrients compared with 12.5% on placebo (p = .003, relative risk [RR] = 4.053; NNT = 1.9). Secondary outcomes highlighted significant benefits of micronutrients over placebo on CGI-Severity, parent-reported conduct symptoms and prosocial behavior, and adolescent-reported suicidal ideation. Micronutrients also led to faster improvement in clinician-rated irritability, parent-rated dysphoria, and adolescent-rated quality of life, stress, and prosocial behaviors. Only one side effect differed significantly between groups: temporary diarrhea was more common on micronutrients (20.9%) than on placebo (6.2%; p = 0.02, RR = 3.40). A minority of participants (