Multinutrients as Adjunctive Treatment for Bipolar Disorder: A randomized-controlled trial feasibility study

Abstract Introduction: An open label trial showed reduction in symptoms from a comprehensive micronutrient supplement in combination with Fish Oil for adults diagnosed with bipolar disorder. Methods: A double blinded, randomized, controlled feasibility trial explored the parameters necessary to mount a larger trial. We randomized in a 3:2 ratio to multinutrients or Placebo. We recruited patients diagnosed with bipolar disorder from a family medicine residency clinic. Diagnoses were confirmed via psychiatric interview. The primary outcome measure was change on a composite z-score of the clinical global impressions scale (CGI), the UKU Side Effects Scale, and medication doses. Results: A total of 69 patients were randomized and data was analyzed for 49 patients. The mean difference of the composite z-score for the multinutrient group was 0.63 (SD; 0.25) and for the Placebo Group 0.47 (SD=0.22). Independent samples t-testing gave a t-score for that difference of 2.429 (p = 0.019; ES = 0.437; 95% CI = -0.556 to -0.053). Significantly more patients in the multinutrient group improved on the CGI (p = 0.04; OR = 4.0; 52% responders vs. 22% in the Placebo Group). All patients improved on the secondary measures with inter-group differences favoring the multinutrient group that did not reach statistical significance. The only adverse events occurring more among the multinutrient group were nausea and loose stools but these were not statistically significant between groups. Conclusions: Multinutrients show promise for adjunctive treatment of bipolar disorder. We observed benefits for patients from closer surveillance, medication adjustment (mostly reduction), and increased human contact.