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Am Fam Physician. 2008;78(4):433

Author disclosure: Nothing to disclose.

Original Article: Herbal and Dietary Supplements for Treatment of Anxiety Disorders

Issue Date: August 15, 2007

to the editor: In early 2002, the U.S. Food and Drug Administration (FDA) issued a letter to health care professionals recommending that persons with liver disease or those who were taking drugs that may affect the liver should consult a physician before using kava because of rare cases of liver toxicity in kava users.1 In a consumer advisory, the FDA urged people using kava who developed symptoms of liver disease to consult a physician.2 Subsequently, many studies have examined the safety and potential mechanisms of toxicity of kava. Despite FDA warnings, kava remains an extremely popular supplement in the United States. Kava is used most frequently to treat anxiety, depression, insomnia, stress, and menopausal symptoms. The appearance of severe liver toxicity in patients in Europe followed decisions to import the stems and leaves of the kava plant even though traditional preparations used only the roots. Research has identified toxic compounds found in the stem and leaves that are not found in the kava root. The World Health Organization has joined with the Natural Standard Research Collaboration (NSRC) to issue an updated report on the hepatotoxicity of kava.3

The use of the more toxic parts of the kava plant may explain some instances of hepatotoxicity, but psychosocial factors may also contribute to increased use and possible exposure to toxic effects from dietary supplements. Patients taking dietary supplements often do not report this use to their physicians. Kava downregulates the liver enzymes that metabolize many prescribed medications, including the benzodiazepines and selective serotonin reuptake inhibitors commonly used to treat anxiety disorders. As a result, the combination of kava and prescription anxiety medications places patients at risk for hepatotoxic drug interactions.

In our review in AFP of herbal and dietary supplements for treatment of anxiety disorders, we sought high-quality evidence that could support the use of any dietary supplements for the treatment of anxiety disorders. We found solid evidence that kava, when taken for mild-to-moderate generalized anxiety disorder (GAD) for less than 24 weeks, produced significant reductions in symptoms with side effects similar to commonly prescribed medications for this disorder. There is no data supporting kava use for other anxiety disorders, and we did not review the evidence for other uses. The FDA warnings in 2002 are still in effect and are echoed widely by respected sources such as the Natural Medicines Comprehensive Database,4 the National Center for Complementary and Alternative Medicine,5 and the NSRC research collaboration.6 Given the lack of regulation for supplements and the absence of clear indicators of who is at risk for toxic reactions, cautionary statements continue to be justified. Physicians who supervise patients taking kava for the treatment of GAD should take care to avoid the following: (1) high dosages (more than 300 mg per day); (2) combining kava with hepatoactive agents; (3) using non-root preparations; and (4) exposure for longer than 24 weeks. Use of WS1490 standardized kava extract is also recommended. If these safety precautions are followed, kava can be appropriate therapy for selected patients diagnosed with GAD.

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This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

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