Taking nutritional supplements in addition to antidepressants may help reduce clinical depression, according to a new study out of the University of Melbourne and Harvard. Omega-3 fish oils, S-adenosylmethionine (SAMe), methylfolate, and Vitamin D were shown to be effective in boosting the positive effects of the antidepressants.

The researchers reviewed several international studies to conclude that nutritional supplements could improve outcomes for people on antidepressants. Omega-3 fish oil, in particular, proved to be the most effective. In the past, researchers have linked Omega-3 fatty acids, which comprise the fish oil and are found in fatty fish like salmon, to improved mood and depressive symptoms.

“The strongest finding from our review was that Omega-3 fish oil, in combination with antidepressants, had a statistically significant effect over a placebo,” said Dr. Jerome Sarris, lead author of the study, in a statement. “Many studies have shown Omega-3s are very good for general brain health and improving mood, but this is the first analysis of studies that looks at using them in combination with antidepressant medication. The difference for patients taking both antidepressants and Omega-3, compared to a placebo, was highly significant.”

The notion that supplements or vitamins could make antidepressants work better isn’t new. One-third of patients taking antidepressants see a partial response to the drugs, and another third don’t see any results at all, making psychiatrists keen to find combinations to ameliorate their efficacy for unique patients. A few years ago, doctors started noticing that some patients on antidepressants who were also taking Deplin, a prescription medical food pill consisting of the supplement l-methylfolate, experienced a boost in their mood. For some who had not seen an improvement in symptoms from taking antidepressants alone, the medication was more effective once they added the Deplin. Most recently, a study found that Omega-3 fatty acids helped relieve major depressive disorder, particularly among those taking antidepressants.

However, the researchers note the results should be taken with a grain of salt. It’s notoriously difficult and controversial proving nutritional supplements and vitamins effective. For that reason, the researchers encourage people to first discuss potential supplements with their doctor, especially if they’re looking to use it in collaboration with antidepressants. “We’re not telling people to rush out and buy buckets of supplements,” Sarris said in the statement. “Always speak to your medical professional before changing or initiating a treatment.”

Regardless, the researchers hope that with further research they’ll be able to develop and tailor new therapies for people whose antidepressants aren’t entirely working. “Millions of people in Australia and hundreds of millions worldwide currently take antidepressants,” Sarris said. “There’s real potential here to improve the mental health of people who have an inadequate response to them. … 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.”

Source: Sarris J, et al. American Journal of Psychiatry. 2016.