Teens irritability responded to a mega-vitamin, especially with disruptive mood dysregulation
STUDY: Rucklidge JJ et al, J Am Acad Child Adolesc Psychiatry 2026
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Health Research Council of New Zealand, University of Canterbury Foundation, and the School of Psychology, Speech and Hearing. Micronutrients and matching placebo were supplied free by Hardy Nutritionals (but they did not fund it).
Background
Disruptive mood dysregulation disorder (DMDD) entered the DSM in 2013. The diagnosis wasn’t well understood, but we needed a way to recognize children with mood and behavioral problems who were otherwise getting misdiagnosed with bipolar disorder.
A decade later, small trials suggest benefits with SSRI (as augmentation to stimulant) and psychotherapy (CBT, DBT, and interpersonal).
Micronutrients have improved similar symptoms in ADHD, and this is the first trial to test these mega-vitamins in teens with DMDD and other non-specific irritatability.
The Study
- 132 teens (age 12-17) with clinically significant irritability, randomized evenly to a micronutrient formula or placebo for 8 weeks; 117 completed
- 30 carried a DMDD diagnosis
- Intervention: Daily Essential Nutrients with added Vitamers, taken with food and water, titrated as 1 three times a day (TID) for 2 days, then increase by 3 caps/day every 2 days until reaching 4 TID.
Results
Micronutrients surpassed placebo on the primary outcome, a measure of global improvement (CGI):
The effect size was small (0.30 to 0.36), but larger in teens with DMDD (1.06-1.44). Lower-income teens were also more likely to respond.
Parent-rated emotional reactivity, though not on total irritability. Secondary outcomes, including severity, conduct symptoms, prosocial behavior, and suicidal thoughts, improved more with micronutrients.
Side Effects
Temporary diarrhea was more common on micronutrients (21% vs 6%). No other side effect differed between groups, and there were no serious drug-related adverse events.
Limitations
Only 30 participants had DMDD, so that subgroup result needs replication. The placebo response was high, and there was no time-by-treatment effect on any primary outcome, so you can’t tell patients this works faster than nothing.
More on Micronutrients
The theory behind these mega-vitamins is that food processing and industrial farming have stripped away many of the micronutrients from the Western diet. The deficit impairs brain function, with effects on neurotransmitter production, neuroplasticity, inflammation, and stress hormones. Some of the ingredients improved mental health in studies of their own: B vitamins, vitamin D, iron, zinc, and magnesium. The ingredients used in this trial are below.
In ADHD, micronutrients improved emotional dysregulation, aggression, and inattention in one large and two small placebo-controlled trials, earning them a place in CANMAT and World Federation of Biological Psychiatry guidelines for CAM therapies. The trials support two brands, which have similar ingredients: EMPowerplus and Daily Essential Nutrients.
Practice Implications
- The micronutrients used in the study are available from Hardy Nutritionals. They are safe and free of drug interactions, but are pricey.
- Most of the ingredients can also be obtained from a healthy diet.
- Learn more about how to use micronutrients in our Carlat interview with the lead author, Julia Rucklidge.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
