Can Supplements and Herbs Help Cure the Blues?

In one nationally representative survey, researchers found that 42 percent of Americans overall—and 54 percent of those with severe depression—reported using some type of complementary therapy in the previous year. Because herbal and dietary supplements are among the most popular forms of complementary therapies, we're providing a quick review of four supplements that are considered to be safe and effective for some patients.

But three cautions apply. First, most studies of herbal remedies have enrolled patients with mild forms of depression, who tend to respond to many therapies—so the findings are unlikely to apply to patients with major depression. Second, herbal products are not FDA-regulated, so quality and ingredients may vary. Third, patients taking any medication should consult with a clinician before taking an herbal product, to avoid possible interactions.

Folic acid

Background

Folic acid is the synthetic form of folate, a B vitamin found in green leafy vegetables, citrus fruits, beans, and fortified bread and cereals. Among other functions, folic acid helps the brain produce neurotransmitters, including serotonin, which affects mood. Folate deficiency is common among people who are depressed, and people with low blood levels of folate are less likely to get relief from antidepressant drugs.

Evidence

A review by the Cochrane Collaboration analyzed randomized controlled studies, and found only three that met its criteria. One study showed that folic acid supplementation did not provide significant benefit in relieving depressive symptoms when used on its own, but the two other studies showed that it may boost response to antidepressants.

One placebo-controlled study that enrolled patients with moderate to severe depression, for example, found that taking 500 micrograms (mcg) of folate with 20 milligrams (mg) of fluoxetine (Prozac) boosted response to the antidepressant in women, but not in men—possibly because men require higher doses of folic acid supplements than women.

No data are available about efficacy in children.

Caveats

Longer-term research may be needed, because some believe folate acts gradually and cumulatively to relieve depression.

Dosing

Optimal dosage is unclear.

Cautions

Taking more than 1,000 mcg of folic acid per day exceeds the federally advised intake level for adults and can mask a vitamin B-12 deficiency. Anyone considering folate supplements should have a blood test to check B-12 levels before beginning therapy.

Sources

• Coppen A, et al. "Enhancement of the Antidepressant Action of Fluoxetine by Folic Acid: A Randomized, Placebo-Controlled Trial," Journal of Affective Disorders (Nov. 2000): Vol. 60, No. 2, pp. 121–30.
• Natural Standard Research Collaboration. "Folate (Folic Acid)," August 1, 2006. Accessed via the Web site www.nlm.nih.gov/medlineplus.
• Taylor MJ, et al. "Folate for Depressive Disorders," Cochrane Database of Systematic Reviews (2003): Doc. No. CD003390.

SAMe

Background

SAMe (S-adenosyl-L-methionine) is a substance made in the body that boosts production of the neurotransmitters serotonin, norepinephrine, and dopamine—which may be low in patients with depression. SAMe supplements may help restore levels to normal.

Evidence

Six of eight placebo-controlled trials found that SAMe was more effective than placebo. Another eight studies compared SAMe to a tricyclic antidepressant; six concluded SAMe was equivalent to the drug.

Two other studies suggested that combining SAMe with a tricyclic antidepressant speeds treatment response, while a third reported that the supplement may also boost response in patients who are not fully benefiting from a selective serotonin reuptake inhibitor (SSRI) or venlafaxine (Effexor).

Caveats

Less is known about how SAMe supplementation alone compares to treatment with an SSRI. Research is also needed about optimal dosing.

There is no evidence that this supplement is effective in children.

Dosing

The recommended dosages range from 400–1,600 mg per day, although some patients may need 3,000 mg per day to alleviate symptoms.

Cautions

Although SAMe causes few side effects on its own, combining it with an antidepressant may cause serotonin syndrome (see below).

Sources

• Alpert JE, et al. "S-adenosyl-L-methionine (SAMe) as an Adjunct for Resistant Major Depressive Disorder: An Open Trial Following Partial or Nonresponse to Selective Serotonin Reuptake Inhibitors or Venlafaxine," Journal of Clinical Psychopharmacology (Dec. 2004): Vol. 24, No. 6, pp. 661–64.
• Mischoulon D. "Update and Critique of Natural Remedies as Antidepressant Treatments," Psychiatric Clinics of North America (March 2007): Vol. 30, No. 1, pp. 51–68.