Applied Evidence

Leveraging CAM to treat depression and anxiety

Author and Disclosure Information

Conventional medications and psychotherapy are still first-line treatments, but certain complementary and alternative strategies have value as adjunctive measures.


› Consider standardized preparations of St. John’s wort for the treatment of mild to moderate depression in certain patients. A

› Encourage patients with depression or anxiety to engage in exercise and meditation to help with symptom management. A

› Consider methylfolate and S-adenosyl methionine as adjunctive treatments to improve depression. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Almost 8% of Americans ages ≥ 12 years have depression and 19.1% of Americans ages ≥ 18 years have experienced an anxiety disorder in the past year.1,2 Furthermore, suicide, which can result from depression and anxiety, is the 10th leading cause of death in the United States, claiming about 40,000 to 49,000 lives per year since 2012, with increasing yearly rates.3 While multiple conventional medication and therapy treatments are available, patients remain interested in complementary and alternative medicine (CAM) options. According to the National Center for Complementary and Integrative Health, more than 30% of American adults use CAM treatments.4

This article provides an overview of the evidence for commonly used CAM treatments for unipolar depression and anxiety in adults. It is designed to serve as a useful resource when patients are interested in looking beyond conventional medications.

St. John’s wort: ‘Yes’ for depression; ‘no’ for anxiety

Hypericum perforatum, more commonly known as St. John’s wort, is a widely used antidepressant, especially in Europe where it is prescribed, rather than offered over the counter as it is here. Its mechanism of action is not completely understood because its various constituents have different neuropharmacologic activities.5,6

A 2008 Cochrane review evaluated 29 randomized, double-blind studies (N = 5489) that compared St. John’s wort with placebo or standard antidepressants in the treatment of depression.7 St. John’s wort was found to be superior to placebo and comparable to standard antidepressants. More recently, a 2017 meta-analysis of 27 studies (N = 3808) had similar findings.8 In patients with mild-to-moderate depression, St. John’s wart produced rates of remission that were comparable to those produced by selective serotonin reuptake inhibitors (SSRIs) but with a lower discontinuation rate.

Mood disorders other than depression. Studies do not support a role for St. John’s wort in the treatment of anxiety disorders. There are no trials that assess the efficacy of St. John’s wort for the reduction of symptoms of general anxiety disorder as a primary outcome of treatment. Some small clinical trials have investigated the efficacy of St. John’s wort in obsessive-compulsive disorder and social anxiety disorder. In those studies, St. John’s wort performed no better than placebo.9,10

A few words of caution. Preparations of St. John’s wort in the United States are not standardized, so St. John’s wort should be used in America with caution. Furthermore, long-term use of St. John’s wort for depression is questionable given that most studies have evaluated only up to 12 weeks of use.8

In patients with mildto-moderate depression, St. John’s wort produced rates of remission that were comparable to those produced by SSRIs— with a lower discontinuation rate.

If used, studies indicate that the St. John’s wort extract that should be used is 0.3% hypericin or 5% hyperforin administered in a dosage of 300 to 400 mg tid.7,8,11 Physicians and patients can use to find St. John’s wort brands that have met specified quality criteria based on independent laboratory studies. This Web site can also be used to investigate the quality of the brands available for the other supplements discussed in this article.

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