Findings from a new study published in The American Journal of Psychiatry suggest that some nutritional supplements can enhance the efficacy of antidepressants for patients with depression.

The use of nutraceuticals as adjunctive therapy can potentially impact some neurochemical pathways involved in depression. Though various studies have been conducted regarding this topic, no meta-analysis has been conducted to date. Study authors from the University of Melbourne and Harvard University performed a systematic search up to December 2015 for clinical trials using adjunctive nutrients for depression. They used a random-effects model to analyze the standard mean difference between treatment vs. placebo in the change from baseline to endpoint. 

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The data showed mainly favorable results for similar studies that evaluated S-adenosylmethionine (SAMe), methylfolate, omega-3 (mainly EPA or ethyl-EPA), and vitamin D. Some isolated studies demonstrated positive results for creatine, folic acid, and an amino acid combination. Researchers found nonsignificant results for inositol and mixed results for zinc, colic acid, vitamin C, and tryptophan. 

A meta-analysis that compared omega-3 to placebo indicated a significant and moderate-to-strong effect in favor of omega-3. In contrast, a meta-analysis comparing folic acid to placebo showed a nonsignificant difference between the two agents. Jerome Sarris, PhD, MHSc, head of the ARCADIA Mental Health Research Group, added, “Medical practitioners are aware of the benefits of omega-3 fatty acids, but are probably unaware that one can combine them with antidepressant medication for a potentially better outcome.”

Apart from minor gastrointestinal disturbances, no major adverse effects were documented in the studies. 

The available evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to decrease depressive symptoms, the authors concluded.

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