Finding ways to make antidepressants more effective could help the millions of people who take them for depression. Now early research suggests pairing the medication with certain supplements, including omega-3 fish oil and vitamin D, could be one way to do so.
In the new study published in the American Journal of Psychiatry, researchers looked at what happened when some supplements were paired with antidepressants. They combed 40 clinical trials that tested antidepressants taken in conjunction with omega-3s, vitamin D and zinc—nutritional supplements sometimes used to help treat depression, often called nutraceuticals.
The researchers found that people who took omega 3s with antidepressants reported fewer depressive symptoms compared to people taking antidepressants alone. While omega-3s had the most powerful effect, other nutraceuticals also improved the effects of antidepressants, including S-adenosylmethionine, a synthetic form of a compound formed naturally in the body that helps maintain cells and brain chemicals; methylfolate, a form of folate; and vitamin D. Mixed results were seen for zinc, folic acid, vitamin C and the amino acid tryptophan.
Research suggests that the supplements tested in the studies target some of the similar brain processes and pathways as antidepressants. Though recent research has been somewhat mixed, omega-3 supplements have been found to potentially benefit parts of the brain thought to be linked to depression and mood.
“Omega-3 fatty acids appear to exert a range of biological activity which may be beneficial for improving mood,” says study author Jerome Sarris, head of the ARCADIA Mental Health Research Group at the University of Melbourne, in an email. “The question remains whether when combined with medication, a unique beneficial interactive effect is occurring, or whether it is due to two distinct yet complementary mood elevating effects.”
There’s a lot experts don’t know about the drugs, including how exactly they work and why some people respond to them better than others. Antidepressants also appear to have a powerful placebo effect; recent data suggests that anywhere from 30-45% of response to an antidepressant is due to the power of placebo. Figuring out how to make the drugs more effective could help a lot of people.
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“I’m cautiously optimistic about the results, which show some positive benefit,” says Dr. Richard Friedman, professor of clinical psychiatry at Weill Cornell Medical College who was not involved with the study. “There are many methodology concerns about individual studies, like small sample sizes. But the results of this study clearly justify more rigorous large randomized clinical trials of nutraceuticals in the treatment of depression.” Nutraceuticals are largely unregulated, he says, “so quality and purity is a concern.”
The researchers did not turn up major safety issues and found that overall the supplements were well-tolerated; the most commonly reported side effects were constipation, stomach upset and diarrhea. Still, people should consult with their physician about what supplements and medications to take, they conclude. Based on the findings, which need to be replicated in larger studies, taking supplements alongside antidepressants may be a low-cost way to improve treatment.