Micronutrients as Adjunctive Treatment for Bipolar Disorder: A Randomized, Double-Blinded, Controlled Trial

Abstract

ObjectivesAn open label trial had suggested that a comprehensive micronutrient supplement, Empower Plus Advanced, in combination with Fish Oil, would be helpful in reducing symptom burden in adults diagnosed with bipolar disorder.MethodsWe designed a double-blinded, randomized, controlled feasibility trial to explore the parameters necessary to mount a large-scale clinical trial. We aimed to enroll 97 participants and randomize in a 3:2 ratio to Vitamins or Placebo. We recruited patients from a family medicine residency clinic in Maine who were diagnosed in the electronic health record as having bipolar disorder. Diagnoses were confirmed via psychiatric interview or chart review (for obvious cases). The primary outcome measures were changes on the clinical global impressions scale (CGI), changes on the UKU Side Effects Scale, and changes in medications doses.ResultsA total of 69 patients were actually randomized and data were analyzed for 49 patients. The cost per participant was higher than expected due to increased regulatory requirements imposed by our Institutional Review Board (IRB) related to concerns about the hazards of micronutrient supplementation for psychiatric patients. In non-parametric chi-square analysis, significantly more patients in the Vitamin group improved on the CGI over the course of their participation in the study (p = 0.04). However, in parametric analysis the average improvement was not statistically significant between the two groups. All patients showed significant improvement over time in CGI (p = 0.0001) with statistically significant reductions in medication doses and side effects. The only adverse events occurring more among the Intervention group were nausea and loose stools but were not statistically significant.ConclusionsWe suspect the benefits of closer surveillance, medication adjustment (mostly reduction), and human contact overshadowed the potential benefits of micronutrients. Future studies would do well to use a four-month lead-in period during which medications can be adjusted and participants can decide if they are willing to take vitamins 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.Funding SourcesThe Foundation for Excellence in Mental Health.