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Ideally, you never tackle depression with just one weapon.

Effective medications work better when you combine them with psychotherapies like cognitive behavioral therapy, and when you add in lifestyle changes like regular exercise and a healthy diet, you further increase your chances of symptoms improvement.

And sometimes, complementary supplements can also play a role, as an adjunct treatment to further improve the odds of really getting better.

But with so many supplements on the market all promising so much – which ones really deliver?

Here’s a quick overview of some of the most promising supplementary medicines, with research examples of their efficacy, and cautions, where applicable, about their dangers.

4 Clinical Research-Backed Depression Treatment Supplements:

St John’s Wort

Probably the most commonly used herbal depression supplement, St John’s Wort is a yellow flowered weed that grows widely throughout the US. People with depression most commonly take capsules of St John’s Wort powder (typically 300 mgs) three times a day, and there is some research evidence that it works as well as antidepressants in the treatment of mild to moderate depression - while inducing fewer unpleasant side effects.

A Cochrane Review of 29 clinical studies on St John’s Wort as a depression treatment found that the supplement consistently worked better than placebo as a treatment for mild to moderate depression – working about as well as standard antidepressants – and that people reported fewer side effects with the supplement than with typical antidepressants.1


Studies have not found St John’s Wort effective as a treatment for more serious depression and it can limit the effectiveness of some medications, such as birth control pills and antidepressant medications, among others. Obviously, you need to consult with your doctor before initiating a course of this, or any, herbal medicine.


Low levels of the neurotransmitter serotonin are associated with depression.

5-HTP is a necessary precursor for the production of serotonin and so using 5-HTP supplements can result in more serotonin and less depression. Many common antidepressants, such as Zoloft or Prozac also work in the brain to increase serotonin levels to reduce depression symptoms. In some ways, 5-HTP may be considered a more natural form of a serotonin based antidepressant.

Manufacturers derive 5-HTP supplements from the ground seeds of the griffonia simplicifolia plant.

A review of studies shows that 5-HTP works better than placebo as a treatment for depression, but because of side effects, an overall lack of solid clinical research and some lingering questions about the supplement’s safety, most experts do not endorse its use.2


The supplement can cause side effects such as nausea and vomiting. More worrisome, the use of tryptophan supplements has been linked to a possibly fatal syndrome called, eosinophilia-myalgia syndrome. Due to some lingering uncertainty about its safety and because existing serotonin based antidepressants work well, experts do not generally endorse the use of 5-HTP as a treatment for depression.

SAMe (S-adenosyl-L-methionine)

SAMe, which is pronounced ‘Sammy’, is a chemical your body manufactures in the liver which is involved in over 40 metabolic processes, including the synthesis of neurotransmitters like dopamine. Although researchers aren’t exactly sure how it influences mood, SAMe is believed to have antidepressant properties through some moderation of neurotransmitters in the brain.3

Research studies have found that up to 1600 mgs of SAMe daily work better than placebo and about as well as tricyclic anidepressents in the treatment of depression. It seems well tolerated and it may begin to work more quickly than other antidepressants, which can take a number of weeks to become effective. Unfortunately, there have been no high-quality large-scale clinical trials on the effectiveness of SAMe nor any large-scale clinical trials comparing the effectiveness of SAMe to SSRI antidepressants.


SAMe is not recommended for people with bipolar disorder as it can induce mania. People should not take SAMe without first consulting with their doctor as it may alter the potency and effectiveness of other antidepressant medications.4

Folate or L-methylfolate

If you have depression, it’s a good idea to talk to your doctor about whether you should get your folate levels checked out.

People with depression who also present with low blood cell folate levels are less likely to get full effectiveness from their antidepressants, typically present with more severe symptoms of depression and typically wait longer before seeing the positive results of antidepressant therapy.5

Studies of people with depression who use folate supplements or L-methyfolate (which is a form of folate which crosses the blood brain barrier) have demonstrated a role for the supplement in the treatment of depression.6

In research studies, patients with depression who added folate or L-methylfolate supplements as an adjunct to antidepressant therapy got better results than people who used antidepressants and a placebo.7 8


L-methylfolate may increase the risk of seizures in people already prone to having them and may accelerate colon tumor growth for people with colon cancer.

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Page last updated Jun 24, 2012

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