Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials.
OBJECTIVE
Studies using augmentation of pharmacotherapies with nutraceuticals in bipolar disorder (BD) have been conducted and preliminary evidence in many cases appears positive. To date, however, no specialized systematic review of this area has been conducted. We present the first systematic review of clinical trials using nutrient-based nutraceuticals in combination with standard pharmacotherapies to treat BD. A subsequent aim of this report was to discuss posited underlying mechanisms of action.


METHODS
PubMed, CINAHL, Web of Science, and Cochrane Library databases, and grey literature were searched during mid-2010 for human clinical trials in English using nutraceuticals such as omega-3, N-acetyl cysteine (NAC), inositol, and vitamins and minerals, in combination with pharmacotherapies to treat bipolar mania and bipolar depression. A review of the results including an effect size analysis (Cohen's d) was subsequently conducted.


RESULTS
In treating bipolar depression, positive evidence with large effect sizes were found for NAC (d=1.04) and a chelated mineral and vitamin formula (d=1.70). On the outcome of bipolar mania, several nutraceuticals reduced mania with strong clinical effects: a chelated mineral formula (d=0.83), L-tryptophan (d=1.47), magnesium (d=1.44), folic acid (d=0.40), and branched-chain amino acids (d=1.60). Mixed, but mainly positive, evidence was found for omega-3 for bipolar depression, while no evidentiary support was found for use in mania. No significant effect on BD outcome scales was found for inositol (possibly due to small samples).


CONCLUSIONS
BD treatment outcomes may potentially be improved by additional use of certain nutraceuticals with conventional pharmacotherapies. However, caution should be extended in interpreting the large effects of several isolated studies, as they have not yet been replicated in larger trials.
Department of Psychiatry, Faculty of Medicine, University of Melbourne, The Melbourne Clinic2 Salisbury Street, Richmond, Victoria 3121, Australia. jsarris@unimelb.edu.au
Jerome
J
Sarris
David
D
Mischoulon
Isaac
I
Schweitzer
D000596:Amino Acids / Q000627:therapeutic use; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000178:diet therapy* / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D016208:Databases, Factual / Q000706:statistics & numerical data; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006801:Humans; D008903:Minerals / Q000627:therapeutic use; D016896:Treatment Outcome; D014815:Vitamins / Q000627:therapeutic use
D000596:Amino Acids; D018692:Antimanic Agents; D015525:Fatty Acids, Omega-3; D008903:Minerals; D014815:Vitamins