Efficacy and safety of a vitamin-mineral intervention for symptoms of anxiety and depression in adults: A randomised placebo-controlled trial "NoMAD"

Background: Anxiety and depression are increasingly burdening society. We investigated whether micronutrients (vitamins and minerals), improve anxiety and depression symptoms in an adult community setting.Methods: Participants (n = 150) describing functionally-impairing symptoms of anxiety/depression randomly received micronutrients or placebo for 10 weeks. Primary outcome measures were Patient Health Questionnaire 9 (PHQ-9), Generalised Anxiety Disorder Scale-7 (GAD-7), and Clinical Global Impression-Improvement scale (CGI-I). They were monitored online with regular phone contact with a clinical psychologist.Results: Linear mixed-effects modelling showed significant improvements in both groups, with the micronutrient group improving significantly more quickly on both the PHQ-9 (t =-2.17, p = 0.03) and the GAD-7 (t =-2.23, p = 0.03). Subsequent models with covariates showed that participant characteristics moderated time-by-group interactions; micronutrients provided fastest improvement relative to placebo for younger participants, those from lower socioeconomic groups and those who had previously tried psychiatric medication. On the CGI-I, there were no group differences at end-point ((F1,148) = 1.36, p = 0.25, d = 0.19, 95 % CI [-0.13 to 0.51]), with 49 % of the micronutrient and 44 % of the placebo groups being identified responders. Participants on micro nutrients had significantly increased bowel motions compared with placebo. There was no increased suicidal ideation, no serious adverse events and the blind was adequately maintained. Drop out was low at 8.7 %. Limitations: The improvement under placebo and lack of formal diagnoses limit generalizability.Conclusions: Despite limited clinician contact, all participants improved significantly, though improvements were faster with micronutrients. Participants in some subgroups demonstrated a lower response to placebo, identifying where micronutrients may offer greatest potential as an intervention.