Review of Nutritional Supplements for the Treatment of Bipolar Depression

Abstract

Many patients view psychotropics with skepticism and fear and view nutritional supplements as more consistent with their values and beliefs. The purpose of this review was to critically evaluate the evidence base for nutritional supplements in the treatment of bipolar depression (BD). A literature search for all randomized, controlled clinical trials using nutritional supplements in the treatment of BD was conducted via PubMed and Ovid MEDLINE computerized database. The studies were organized into essential nutrients/minerals, nonessential nutrients, and combinations of nutritional products. Among essential nutrients/minerals, omega-3-fatty acids (O3FAs) have the strongest evidence of efficacy for bipolar depression, although some studies failed to find positive effects from O3FAs. Weak evidence supports efficacy of vitamin C whereas no data support the usefulness of folic acid and choline. Among nonessential nutrients, cytidine is the least supported treatment. Studies of N-acetylcysteine have not resolved its efficacy in treating acute depressive episodes relative to placebo. However, one study demonstrates its potential to improve depressive symptoms over time and the other, though nonsignificant, suggests it has a prophylactic effect. Studies of inositol have been mostly negative, except for 1 study. Those that were negative were underpowered but demonstrated numerically positive effects for inositol. There is no evidence that citicholine is efficacious for uncomplicated BD depression, though it may have value for comorbid substance abuse among BD patients. Finally, combination O3FA-cytidine lacks evidence of efficacy. The findings of this review do not support the routine use of nutritional supplements in the treatment or prophylaxis of BD depression. Studies with more rigorous designs are required before definitive conclusions can be made. Despite the inadequacy of the existing data, clinicians should remain open to the value of nutritional supplements: after all, lithium is a mineral too.

The Role of Dietary Supplements in Depression and Anxiety – A Narrative Review

“…In this study, natural Vit C intake seems to be beneficial for depression, but Vit C from dietary supplements has no effect [36]. This implicates that various supplements have influence on depression or being influenced by depression [32][33][34][35][36].…”

“…Both studies refer only to small sample sizes. Rakofsky et al undertook a literature search on PUFA, Vit C, NAC, inositol, folic acid, and citicholine and found inconsistent correlation between PUFA, Vit C, and citicholin and bipolar disorder, no correlation between folic acid, choline and cytidine-PUFA and bipolar disorder [34]. Hashimoto et al also found significantly (p = 0.0029) higher levels of Vit C in the cerebrospinal fluid CSF of elderly people with depression, but no cognitive decline in comparison with healthy controls [35].…”

Common use of dietary supplements for bipolar disorder: a naturalistic, self-reported study

“…The long-term use of supplements had no impact on self-reported mood symptoms, although individual supplements were not analyzed. While the efficacy of dietary supplements in the treatment of bipolar disorder is outside the scope of this analysis, most review articles do not recommend routine use of dietary supplements yet recognize that some products have potential adjunctive benefit (Andreescu et al 2008 ; Rakofsky and Dunlop 2014 ; Sagduyu et al 2005 ; Sarris et al 2011 ). However, adverse effects of some supplements may destabilize mood (Ernst 2003 ; Werneke et al 2006 ).…”

Dietary Omega-6/Omega-3 and Endocannabinoids: Implications for Brain Health and Diseases

“…Supplementation of food supply with ω-3 PUFAs constitutes thus an interesting strategy for the prevention and treatment of mood and anxiety disorders, in particular because of the low side effects expected compared to pharmacological agents. Several trials have been conducted in this context, however, meta-analyses reported mitigated outcomes so far [129,133]. Some trials showed no convincing effect while others demonstrated that ω-3 supplementation for 8-12 weeks have significant positive effects, notably because it improves the efficiency of antidepressants and thus increases the proportion of remission [134].…”