Multi-nutrients as Adjunctive Treatment for Bipolar Disorder: A randomized-controlled trial

Introduction: An open-label trial suggested that a comprehensive micronutrient supplement, Empower Plus Advanced, in combination with Fish Oil, could reduce symptoms in adults with bipolar disorder. A double-blind, randomized, controlled feasibility trial explored the parameters necessary for a large-scale trial. Methods: Participants (N=69) from a family medicine training clinic with diagnoses of bipolar disorder in the electronic health record were randomized in a 3:2 ratio to Multi-nutrients or Placebo. Diagnoses were confirmed via psychiatric interview or chart review (for obvious cases). The primary outcome measure was change on a composite z-score combining changes on the clinical global impressions scale (CGI), changes on the UKU Side Effects Scale, and changes in medication doses. The GLM repeated measures procedure of SPSS compared continuous outcome measures. Chi-square testing compared responders to non-responders. Results: Data were analyzed for 50 participants. The mean difference of the composite z-score for the primary outcome variables was statistically significant (p = 0.019) and for the composite z-score of all variables (primary and secondary) combined (p = 0.047). In non-parametric chi-square analysis, significantly more in the Nutrient group improved on the CGI (rated 1 or 2) (p = 0.04; OR = 4.0; 52% responders vs. 22% in the Placebo Group). All secondary outcome measures showed nonsignificant trends in the expected direction. Patients in both groups made significant improvement in all measures. The only adverse events occurring more among the Multi-nutrient group were nausea and loose stools, not statistically significant. Conclusions: Multi-nutrients show promise for adjunctive treatment of bipolar disorder. We observed substantial benefits for all patients of closer surveillance, medication adjustment (mostly reduction), and increased human contact. Future studies would benefit from use of a longer lead-in period during which medications can be adjusted and participants can decide if they are willing to take Multi-nutrients for an extended time. Our data suggest that primary care patients with bipolar disorder would fare better on lower medications doses and more frequent visits. Further clinical trials are warranted.