Do Adjunctive Neutraceuticals Help Relieve Depression?

Using adjunctive neutraceuticals together with antidepressants can be helpful in reducing depressive symptoms, according to a new systematic review and meta-analysis published in the June 1, 2016 issue of the American Journal of Psychiatry.

An Australian research team analyzed findings of 40 studies encompassing 14 different neutraceuticals and found evidence to support the use of adjunctive S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D in order to alleviate symptoms of depression.

Findings regarding omega-3 were particularly robust. Eight double blind RCTs of omega-3, varying in size (from 20 to 122 participants) and in duration (4 to 12 weeks), met inclusion criteria. Of these, 6 studies showed a statistically significant reduction in depression scores for the treatment group, compared to the placebo group, with a significant effect size of 0.61 (P=0.0009). Ten out of 15 datasets found an effect in favor of 1-carbon cycle neutraceuticals (which consist of SAMe, folic acid, methylfolate, B6, and B12).

Creatine and an amino acid combination yielded positive findings in “isolated studies,” and the researchers stated that these products should receive “tentative consideration.”

The investigators noted that further research is needed to clarify whether zinc, vitamin C, or tryptophan (more specifically, 5-HTP, the active precursor of serotonin) could be of value. They concluded that inositol is “unlikely to have any utility as an adjunctive antidepressant agent,” although some research has suggested it may have utility as depression monotherapy.

Studies were tabulated in 4 separate groups: 1-carbon cycle neutraceuticals (consisting of SAMe and folic acid or related forms, such as methylfolate, B6 and B12); omega-3; tryptophan; other neutraceuticals.

All of the investigated supplements have “mechanistic antidepressant activity underpinning their use,” the researchers emphasized. For example, 1-carbon cycle agents are critical in the methylation processes of monoamines. Omega-3 modulates norepinephrine, dopamine, and serotonin reuptake, degradation, synthesis, and receptor binding.

The study was undertaken in response to the “growing recognition that for many people with a depressive disorder, full remission is either short-lived or absent.” The researchers noted that augmentation and combination approaches with pharmaceuticals are often used in clinical practice. Coadministration of neutraceuticals may “provide an effective and safe approach to enhancing antidepressant effects” either by “synergistically augmenting an antidepressant agent” or by providing “a range of additional biological effects.”

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Sarris J, Murphy J, Mischoulon D, et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016;173(6):575-87.