Can a Supplement Make an Antidepressant More Effective?

Medically Reviewed

Q. Are there any nutritional supplements that can boost the effectiveness of my antidepressant?

A. Possibly. An analysis published in the American Journal of Psychiatry in June 2016 found that when taken with an antidepressant, certain standardized, pharmaceutical-grade nutritional supplements, or “nutraceuticals,” might help further relieve symptoms of depression.

Researchers analyzed 40 studies in which people with depression took an antidepressant plus one of several nutraceuticals.

These included S-adenosylmethionine (SAM-e), L-methylfolate, folinic acid, folic acid, omega-3 fatty acids, vitamins C and D, L-tryptophan, zinc, inositol, amino acids, and creatine. Each supplement had to be taken for a minimum of three weeks.

Overall, researchers found that taking SAM-e, L-methylfolate, omega-3 fatty acids, and vitamin D plus an antidepressant helped further reduce depressive symptoms.

The results were strongest for omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and ethyl-EPA. Some studies suggested that creatine, the active form of folinic acid, and an amino acid combination also might be helpful.

Bottom line

Talk with your doctor before taking any nutritional supplement in addition to your antidepressant. If the antidepressant you’ve been prescribed does not appear to be working very well, your doctor might suggest switching medications or trying some other type of treatment first.

It is also important to note that large doses of vitamins can actually harm health—so both choice and dose of the nutraceutical are essential.