The effect of adjunctive nutraceuticals in bipolar disorder: A systematic review of randomized placebo-controlled trials

Background: Nutraceuticals are a group of compounds of growing interest for mental health professionals. Given the implication of certain nutrients in the onset of bipolar disorder, it has been hypothesized that nutraceuticals might be effective in improving symptoms of the condition (i.e. mania or depression). Our systematic review aimed to evaluate the effectiveness of adjunctive nutraceuticals compared to placebo. Methods: We searched the following databases from inception to February 2019: Web of Science, CINAHL, Embase, and PsycINFO. We included only original randomized controlled trials written in English, testing the efficacy of nutraceuticals in add-on to standard care, compared to placebo, in patients with bipolar disorder. Results: After identifying 6584 potentially relevant publications, we finally included 25 studies, among which six used fatty acids, seven micronutrients, seven amino acids. One study tested probiotics, while in four trials a combination of different types of nutraceuticals was used. Even if some compounds have shown promising results (i.e. fatty acids and N-acetyl cysteine for depression, amino acid drinks and folic acid for mania), the majority of nutraceuticals did not cause significant improvements in comparison to placebo. Limitations: We could not perform a meta-analysis due to the high heterogeneity of trials, which were also affected by some methodological caveats. Conclusions: Evidence regarding the efficacy of adjunctive nutraceuticals in bipolar disorder is inconsistent. Nevertheless, they appear generally free from relevant side effects. Well-designed trials are needed to further explore the potential role of nutraceuticals in different mood episodes.