Do Vitamins and Supplements Make Antidepressants More Effective?

26 April 2016 - Scientific American

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The multibillion-dollar supplement industry spews many dubious claims, but a new study suggests that some nutritional supplements, including omega-3 fatty acids and vitamin D, may boost the effectiveness of antidepressants. If so, the supplements might help relieve symptoms for the millions of people who don’t immediately respond to these drugs.

The meta-analysis—published Tuesday in the American Journal of Psychiatry—reviewed the results of 40 clinical trials that evaluated the effects of taking nutritional supplements in conjunction with several major classes of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants. It revealed that four supplements in particular upped the potency of the medications, compared with a placebo.

The researchers, based at Harvard University and the University of Melbourne, found the strongest evidence for an omega-3 fish oil called eicosapentaenoic acid, or EPA. In general, people with depression who took an antidepressant drug and an omega-3 sourced from fish oil experienced a significant reduction in their symptoms as assessed by a the Hamilton Depression Rating Scale, a common measure used by most of the studies in the review.

The same was true, although to a lesser extent, for S-adenosylmethionine, methylfolate (a form of the B vitamin folic acid) and Vitamin D. A few isolated studies found some benefit from augmenting treatment with creatine, while adding zinc, vitamin C, the amino acid tryptophan and folic acid produced mixed results. The authors deemed all of these supplements relatively safe.

Lead study author Jerome Sarris of the University of Melbourne’s ARCADIA Mental Health Research Group notes that a large percentage of people with depression do not fully respond during one or two trials of an antidepressant. By some estimates, two-thirds don’t respond to the first antidepressant they try and a third fail to get better after several treatment attempts.

“The implications are that clinicians and the public can consider [adding] therapeutic doses of nutrients such as omega-3s as a potential low-cost approach to reducing depression in people who are non-responsive to antidepressants,” he says.  

Sarris and his colleagues speculate that the supplements may enhance the efficacy of antidepressants in various ways, perhaps directly by altering neurostransmitter activity or indirectly by reducing inflammation, known to contribute to depression.

Leading nutritional psychiatry researcher Felice N. Jacka of Deakin University and the University of Melbourne explains that conditions like depression can trigger a cascade of physical concerns that certain supplements, when combined with accepted antidepressant therapies, could help mitigate.

"Serious illnesses such as major depression can result in increased inflammation and oxidative stress, which can in turn result in nutritional deficiencies and a depletion of essential fatty acids,” she notes.

“Nutrients form the substrate of the essential biological processes of the body and brain, so ensuring that nutrient levels are adequate in patients suffering from any serious illnesses is important.”

Doctors and scientists often come down hard on nutritional supplementation. There is little to no scientific evidence backing many of the products crowding the shelves at health food stores and pushed by celebrity doctors. In fact, many come in mega-doses associated with serious side effects. And countless manufacturers produce these supplements, many with no standardized processes and varying degrees of quality control.

Indeed, the supplement industry exists largely outside of any oversight by the Food and Drug Administration (FDA). In December last year, the FDA announced the formation of a new Office of Dietary Supplement Programs to help tighten regulation, but for now when it comes to supplements, consumers often don’t know what they are getting.

Sarris acknowledges that supplements can differ greatly in quality and that his results should be approached with caution.

"We're not telling people to rush out and buy buckets of supplements,” he wrote in a press release accompanying the new paper. “Always speak to your medical professional before changing or initiating a treatment.”

But researchers like Sarris are gradually disentangling potential fact from fiction. A number of vitamins and supplements are coming under scientific scrutiny. Vitamin D in particular has been the focus of a host of recent studies and may be beneficial in treating a variety of conditions, from multiple sclerosis to schizophrenia.  

For brain health, all—or at least most—roads lead to the sea.  

Many small trials have reported associations between omega-3 fatty acids—obtained either through diet or supplements—and improved depression symptoms. In practice, omega-3s derived from fish appear to reach significantly higher blood levels than those sourced from plants. And there is a fast accumulating body of data linking a reduced risk for depression to traditional diets—including the Mediterranean, Scandinavian and Japanese diets—that are high in vegetables, whole grains and fish.

How does the evidence sit in light of the new study’s findings?

“It is important to advise that a balanced whole-food diet is important for physical as well as mental health, and that supplements should not replace this,” Sarris notes. “However, I believe a good diet in addition to select nutraceutical prescriptions can still be recommended in some cases, such as when people have inadequate responses to antidepressant medication.”

As a next step, Sarris believes that researchers should move beyond specific supplements and study augmenting antidepressant treatment with, say, the Mediterranean diet.

Both he and Jacka also feel that more work needs to be done to determine which supplements may benefit patients as individuals, based on their specific nutrient deficiencies, brain conditions and genetic profiles.

“A key imperative for nutritional psychiatry is to develop a clear understanding of what supplements are useful for whom, and under what conditions, and also to understand the baseline factors that might influence nutrient metabolism, such as gut health,” Jacka says.

“This sort of knowledge should help us to begin to design targeted and personalized nutritional interventions for psychiatric illnesses."