1-year naturalistic follow-up of a Randomised Double-Blind, Placebo-Controlled Trial (“NoMAD”) Exploring the Effectiveness of Micronutrients in Improving Symptoms of Anxiety and Depression

Q3 Psychology

Journal of Affective Disorders Reports Pub Date : 2025-04-01 DOI:10.1016/j.jadr.2025.100913

Amy Coët, F. Meredith Blampied, Julia J. Rucklidge

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Abstract

Background

A randomised controlled trial (NoMAD trial) showed micronutrients led to faster recovery from depression and anxiety compared with placebo. The RCT was followed by a 10 week open-label component and then a one year naturalistic review.

Aims

This 1-year follow-up of NoMAD explored the association between dominant treatment at 1-year follow-up with psychiatric outcomes.

Study design/Methods

Ninety-four (63 %) of the original 150 NoMAD participants completed 1-year follow-up. Primary outcomes included Generalised Anxiety Disorder-7 questionnaire (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Modified-Clinical Global Impression-Improvements (MCGI-I). Outcomes were explored based on dominant therapy at 1-year follow-up: Micronutrients (n = 20), Psychiatric Medications (n = 9), and No Treatment (n = 56). Nine participants could not be grouped due to mixed treatments at follow-up.

Results

Regardless of dominant therapy, participants were functioning significantly better at 1-year compared to baseline. There was little change from end of 10 weeks of open-label micronutrient treatment, with the exception of depression scores, which were significantly lower (d = 0.4; p<.001). Most participants had either no or mild depression (78 %) and anxiety (85 %) scores at 1-year follow-up. Those who stayed on micronutrients were those who experienced better response at end of open-label compared with those who stopped or switched to medications. They also showed a greater reduction in health anxiety from end of open-label to 1-year follow-up compared with others. The main reason cited for stopping micronutrients was the cost. Limitations include a third of original sample lost to follow-up and uneven group sizes limit generalisability of results.