Supplements for Depression: What Works, What Doesn’t

The multibillion-dollar market for dietary supplements is filled with products that claim to boost mood or improve depression. But don’t believe everything you read on a label.


What it is: An organic, glucose-like compound that facilitates the transmission of serotonin and other neurotransmitters. People ingest about 1 gram of inositol a day from fruits and vegetables, whole grains, meat, and other foods, and it is also sold as a capsule and powder.

The evidence: The brains of people with depression and bipolar disorder have been shown to have below-average levels of inositol, which prompted researchers to investigate whether inositol supplements could help treat depression.

The initial research was promising. A small study published in 1995 found that taking 12 grams of inositol a day—an amount equivalent to a fistful of the capsules sold in health stores—improved depression symptoms more effectively than placebo. Surprisingly, no one has ever tried to replicate this success. Instead, researchers have studied whether inositol enhances the effects of antidepressants or mood stabilizers—and those studies found no differences between inositol and placebo.

The bottom line: Inositols effectiveness has not been proven. Future research may yet reveal uses for the compound, but in the meantime experts caution against using it as a supplement for depression.


What it is: The polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential to brain function and cardiovascular health. Combined in roughly equal amounts, EPA and DHA are the main ingredients in fish oil, but they are also sold in formulas that include more of one than the other.

The evidence: A link between omega-3 consumption and mood is supported by two main sources of evidence: People with depression have been shown to have lower levels of omega-3 fatty acids, and countries that eat a lot of fish per capita (such as Japan) have lower rates of depression.

The research on omega-3 supplements is mixed, however. In several controlled trials, EPA, DHA, or a combination of the two have been shown to improve the symptoms of depression and bipolar disorder better than placebo—but in nearly all of those studies, the omega-3s were added to antidepressant medications or mood stabilizers, so its unclear whether omega-3s had an independent effect. And in a recent study published in the Journal of the American Medical Association (JAMA), omega-3s plus Zoloft fared no better than placebo plus Zoloft.

The two studies that have used omega-3s on their own for depression have also generated mixed results. One found that 2 grams a day of DHA for six weeks was no better than placebo; the other—which was conducted in children ages 6 to 12—found that a combination of EPA and DHA did outperform placebo.

The bottom line: Although some of the research on omega-3s and mood disorders is encouraging, it remains unclear just how effective omega-3s are, and what formulation and combination of treatments are most beneficial. But omega-3s have few side effects and have cardiovascular and other health benefits, so they may be worth a try (after consulting your doctor first).


What it is: A spice, made from the dried stigmas of crocus plants, that is used in cooking and also in traditional Persian medicine to treat symptoms of depression (among other conditions). Although they can be found online, saffron supplements are not widely available.

The evidence: Little research has been conducted on saffrons effect on mood. But in a series of small controlled trials conducted in Iran in recent years, the spice has performed surprisingly well in treating mild to moderate depression. Delivered in 30-milligram doses a day, saffron has outperformed placebo and has demonstrated an antidepressant effect comparable to Prozac and imipramine (an older tricyclic antidepressant), at least in the short term.

The bottom line: Although more research is needed, saffron appears to be a promising treatment for milder cases of depression. That said, using the worlds most expensive spice as a dietary supplement seems impractical and pricey.

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Ray Hainer
Last Updated: November 10, 2009

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