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

Abstract:

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 teenagers with moderate-to-severe irritability symptoms.

Method: A total of 132 unmedicated teenagers (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/teen 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, 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 teen-reported suicidal ideation. Micronutrients also led to faster improvement in clinician-rated irritability, parent-rated dysphoria, and teen-rated quality of life, stress, and prosocial behaviors. Only one side effect differed significantly between groups: diarrhea was more common on micronutrients (20.9%) than on placebo (6.2%; p = 0.02, RR = 3.40). A minority of participants (<10%) found swallowing pills a challenge.

Conclusion: This RCT provides preliminary evidence that micronutrients may be an effective and safe treatment for teen irritability, with a reassuring reduction in suicidal ideation and, if findings are replicated, may transform outcomes for teens.

Clinical trial registration information: BEAM: Balancing Emotions for Adolescents with Micronutrients:ANZCTR - Registration DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.