DEPRESSION
May 10, 2016

Antidepressants Not Working?

Certain nutraceuticals — omega-3s and others — can boost the effectiveness of antidepressants.

There are antidepressant drugs that can help ease depression, and there are nutritional supplements that are also supposed to improve brain health. Individual studies have suggested that some supplements can boost the potency of antidepressants, particularly among patients on antidepressants whose responses have been disappointing, but it's only recently that enough trials have accumulated to begin to collectively judge them.

Now a review of 40 clinical trials that tested the effect of supplements on depression in people who were also taking antidepressants finds that the combination of antidepressants and supplements like omega-3 fatty acids or s-adenosylmethionine (SAMe) can help relieve depression in people whose response to the drugs alone has been poor.

The potential to improve the mental health of people who have an inadequate response to antidepressant drugs.

The strongest favorable evidence came from trials of omega-3s.

Five out of seven studies found a significant difference in symptoms in people who took omega-3's compared to people who took a placebo. An eighth study had mixed results. In that study, people taking one gram of ethyl-EPA daily showed a significant improvement in symptoms compared to people taking placebo, but those taking two or four grams of ethyl-EPA did not.

“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,” Jerome Sarris, the review's lead author, said in a statement.

Most of the omega-3 studies tested the effect of either eicosapentaenoic acid (EPA) or ethyl-EPA. All were randomized controlled trials where people who did not take omega-3s took a placebo. The patients in the studies were all taking an antidepressant, and their changes in depressive symptoms were measured, most often by the Hamilton Depression Rating Scale (HAM-D).

Three other nutrients also gave positive results — s-adenosylmethionine or sam-E, vitamin D and methylfolate.

There were four studies of the supplement s-adenosylmethionine. Three found a significant positive effect, while the fourth study had mixed results. Positive results were also found for vitamin D (two out of two studies) and methylfolate.

“Millions of people in Australia and hundreds of millions worldwide currently take antidepressants,” said Sarris, head of the ARCADIA Mental Health Research Group at the University of Melbourne in Australia. “There's real potential here to improve the mental health of people who have an inadequate response to them.”

Mixed results were found for several other nutrients — zinc, folic acid, vitamin C and tryptophan, with non-significant results for inositol. No major adverse effects were noted in any study, though some people did report minor digestive disturbances.

Omega-3s, including those contained in fish oil, may interact with drugs ranging from aspirin to birth control pills. And taking them may worsen certain medical conditions. So even though they can be bought without a prescription, it's important to talk to a doctor before taking them.

“We're not telling people to rush out and buy buckets of supplements. Always speak to your medical professional before changing or initiating a treatment,” Dr. Sarris said.

The researchers are currently conducting a new trial that tests the effectiveness of combinations of supplements at easing depression.

Their review appears in the American Journal of Psychiatry.
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