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David Baxter

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Herbal and Dietary Supplements for Treatment of Anxiety Disorders
August 15, 2007
by SY ATEZAZ SAEED, RICHARD M. BLOCH, and DIANA J. ANTONACCI
American Family Physician, Vol. 76 No. 4

Use of complementary and alternative medicine has increased over the past decade. A variety of studies have suggested that this use is greater in persons with symptoms or diagnoses of anxiety and depression. Data support the effectiveness of some popular herbal remedies and dietary supplements; in some of these products, particularly kava, the potential for benefit seems greater than that for harm with short-term use in patients with mild to moderate anxiety. Inositol has been found to have modest effects in patients with panic disorder or obsessive-compulsive disorder. Physicians should not encourage the use of St. John's wort, valerian, Sympathyl, or passionflower for the treatment of anxiety based on small or inconsistent effects in small studies. Although the evidence varies depending on the supplement and the anxiety disorder, physicians can collaborate with patients in developing dietary supplement strategies that minimize risks and maximize benefits. (Am Fam Physician 2007;76:549-56)

Use of complementary and alternative medicine in all of its varieties, such as herbal remedies and dietary supplements, increased from 34 percent of the overall U.S. population in 1990 to 42 percent in 1997.1 Use appears to be twice as great in persons reporting anxiety and depression than in those reporting any other problem, except for back and neck pain.1 Based on results of two large-scale community surveys,2,3 investigators have noted an association between both panic disorder and major depression and the use of complementary and alternative medicine.

Currently, the preferred treatment for anxiety disorders is cognitive behavior therapy and pharmacologic agents. Beta blockers or benzodiazepines are used for time-limited and predictable anxiety disorders, whereas selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, buspirone (Buspar), or monoamine oxidase inhibitors are preferred for chronic or recurrent anxiety disorders.

In recent years, studies using herbal remedies and supplements to treat mild to moderate anxiety disorders have emerged. It is important for physicians to recognize that supplements offer both benefits and risks. By doing so, they can avoid an overly dismissive attitude that discourages patients from disclosing their supplement use. At the same time, understanding the limits of available evidence allows physicians to collaborate with interested patients in developing dietary supplement strategies that minimize risks and maximize benefits.

In this article, the supplements purported to ameliorate anxiety disorders are divided into three groups: herbal supplements, nutritional supplements, and neurotransmitter and hormonal precursors. These divisions are somewhat arbitrary in that all of the products are taken orally, are available over the counter, are marketed with a variety of health claims on the Internet, and are justified by their purported ultimate effects on the neurotransmitter systems that mediate worry, stress, or fatigue symptoms in patients with anxiety disorders.

Information on supplements that claim to be useful or commonly used for anxiety disorders was obtained from several Internet sites, particularly http://www.revolutionhealth.com/drugs-treatments, http://www.healthyplace.com/Communities/Anxiety/treatment/alternative_treatment.asp, and http://www.naturaldatabase.com. Medline via Ovid was used to search for clinical trials, guidelines, and meta-analyses that tested or asserted the effectiveness of these preparations in the treatment of patients with diagnosed anxiety disorders. Table 1 includes suggested supplements that have some evidence of effectiveness for treating anxiety. Only therapies with evidence of effectiveness are discussed in this review.

Table 1. Supplements with Clinical Trial Evidence of Effectiveness or Noneffectiveness for Treating Anxiety (see attached PDF version)

Patients often justify the use of certain preparations on the basis of irrelevant or misleading evidence; to help physicians recognize such preparations, those supplements with no clinical evidence of effectiveness in reducing anxiety are presented in Table 2. Clearly, the vast majority of supplements with purported anxiolytic effects have no evidence of clinical benefit.

Table 2. Supplements with No Clinical Trial Evidence of Effectiveness in Anxiety Disorders (see PDF file)

Herbal Supplements
Kava
There is substantial evidence that kava has a positive effect on the symptoms of anxiety disorders. Table 3 summarizes the evidence on the effectiveness and safety of kava in patients with anxiety disorders.4-12

Table 3. Evidence Regarding the Effectiveness and Safety of Kava in Anxiety Disorders (see PDF file)

Kava dramatically inhibits the cytochrome P450 enzyme used by the liver to metabolize many medications, potentially altering the potency of these other medications.13,14 Thus, it is important to be aware of the risk of drug interactions with kava. Other side effects reported with long-term use include a reversible skin rash or lesion and a yellow tint to the skin, but these reports have not been routine. Despite the absence of long-term data on safety and effectiveness,4,13,15 the evidence shows that short-term use (i.e., up to 24 weeks) can lead to small improvements in generalized anxiety,4 and that short-term risks do not outweigh the benefits.

For patients with mild to moderate anxiety who wish to use "natural" remedies and are not using alcohol or taking other medications that are metabolized by the liver, kava appears to be acceptable for short-term use.

St. John's Wort
St. John's wort is a popular supplement for treating depression but is much less popular for treating anxiety disorders. Studies specifically testing the effects of St. John's wort on patients with anxiety are extremely limited. Table 4 summarizes the evidence for the effectiveness and safety of St. John's wort in the treatment of anxiety disorders.16-23

Table 4. Evidence Regarding the Effectiveness and Safety of St. John's Wort, Valerian, Sympathyl, and Passionflower in Anxiety Disorders (see PDF file)

The evidence of positive effects of St. John's wort on anxiety disorders is weak. No placebo-controlled, randomized, double-blind trials have shown St. John's wort to be effective in treating generalized anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder (OCD), or phobias. The only effective trial involved patients with somatoform disorder, although the relationship between somatoform disorder and anxiety is complex. Much stronger evidence is needed before St. John's wort should be considered a treatment option for patients with diagnosable anxiety disorders.

Hawthorn and California Poppy
A single French study exists of a combination product called Sympathyl,22 which contains 20 mg California poppy, 75 mg hawthorn, and 75 mg elemental magnesium. According to the study, Sympathyl had a very small but positive effect on anxiety. No clinical trials suggest that any of the individual components reduce anxiety in patients with anxiety disorders.

Valerian
Although valerian is often cited as having anxiolytic effects and has been used for centuries by herbalists/physicians to treat nervousness, there are only two small trials involving valerian, neither of which produced clear indications of effectiveness (Table 416-23). Thus, at the present time, there is no clinical evidence of an anxiolytic effect of valerian when compared with placebo in patients with anxiety disorder.

Passion Flower
A single randomized double-blind trial compared 45 drops of passionflower tincture per day to 30 mg per day of oxazepam (Serax; brand no longer available in the United States) for 30 days.23 Investigators noted a marked reduction in anxiety score in both groups, but without a placebo group it was unclear whether other aspects of the milieu could have caused the effects.

Nutritional Supplements
Despite the number of nutritional supplements purported on the Internet to treat anxiety, only inositol, part of the vitamin B complex (B8) and an intracellular second messenger, has evidence suggesting superiority to placebo and even comparability with the SSRI fluvoxamine (Luvox; brand no longer available in the United States). Table 5 summarizes the evidence supporting the effectiveness and safety of inositol in managing anxiety disorders.24-27

Table 5. Evidence Supporting the Effectiveness and Safety of Inositol in Anxiety Disorders (see PDF file)

Inositol appears to have a positive effect on patients with panic disorder; however, its effect on patients with OCD is less clear. Physicians should inform patients that the limited data that exist to date suggest partial responses with a side-effect profile that may be comparable with that of SSRIs.

Neurotransmitter or Hormonal Precursors
The anxiolytic neurotransmitter or hormonal precursors with some evidence of effectiveness are shown in Table 1. The vast majority of neurotransmitter or hormonal precursors that claim to be useful for treating anxiety disorders have no evidence supporting clinical utility. Only 5-hydroxytryptophan appeared to show clinical effectiveness among the precursor preparations. Table 6 summarizes the available evidence relevant to the effectiveness and safety of 5-hydroxytryptophan.28,29

Table 6. Evidence Supporting the Effectiveness and Safety of 5-Hydroxytryptophan in Anxiety Disorders (see PDF file)

Although there is some indication that 5-hydroxytryptophan can reduce anxiety symptoms among patients with anxiety disorders, the evidence is weak. Also, it has been known to cause eosinophilia-myalgia syndrome, a significantly dangerous side effect. Therefore, the risk/benefit ratio does not favor physician support of patients choosing this medication because it is "natural."

Key Recommendations for Physicians
Because use of herbal remedies is increasing, it is important for family physicians to ask their patients about such use. Encouraging data support the effectiveness of some of these products, particularly kava and, to a lesser degree, inositol. Although none of these supplements or products are free of adverse effects, the potential for benefit seems greater than the risk of harm.

The existing data show that the popular supplements St. John's wort, valerian, and omega-3 fatty acids have little therapeutic value for anxiety disorders, and their use should be discouraged in favor of more effective treatments. In addition, many preparations that might be used by patients to reduce anxiety lack evidence of effectiveness with anxiety disorders. The availability of natural treatments that are supported by clinical evidence and the recognition of those that are not will help physicians collaborate with patients using or seeking natural remedies to maximize the potential for benefit and minimize the potential for harm.

REFERENCES
See PDF file.
 

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