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Complementary and Alternative Approaches to Treating Anxiety Disorders

Abstract and Keywords

Studies suggest that between 20%–50% of adults in industrialized nations use some form of complementary and/or alternative medicine (CAM) to either prevent or treat health problems, with higher rates of CAM use observed in nonindustrialized nations. Frequently used approaches include biologically based treatments, manipulative and body-based practices, and mind-body interventions. This chapter summarizes findings from systematic investigations of CAM in treating anxiety disorders and other anxiety states.

Keywords: alternative medicine, anxiety disorders, botanical CAM, complementary medicine, dietary supplement

Studies over the last decade suggest that between 20%-50% of adults in industrialized nations use some form of complementary and/or alternative medicine (CAM) to either prevent or treat health problems (Astin, Maries, Pelletier, Hansen, & Haskell, 1998; Eisenberg et al., 1998). Frequently used approaches include biologically based treatments, manipulative and body-based practices, and mind-body interventions, as well as other CAM approaches listed in Table 1. A more detailed overview of these categories can be found on the Web site for the National Center for Complementary and Alternative Medicine (NCCAM) at http://nccam.nih.gov/health/.

A 2002 survey of U.S. adults revealed that 62% of respondents used CAM in the last year for health reasons. Consistent with earlier surveys in Western societies, the most common conditions prompting use are recurring pain, colds, anxiety and depression, gastrointestinal discomfort, and insomnia (Astin, 1998; Barnes, Powell-Griner, McFann, & Nahin, 2004; Eisenberg et al, 1998). The principal reason for use is the belief that CAM would improve health when used in combination with conventional medical treatment (Barnes et al., 2004).

Among psychiatric outpatients and other adults with self-defined anxiety and/or depression, rates of CAM use can exceed 50% (Kessler et al., 2001; Knaudt, Connor, Weisler, Churchill, & Davidson, 1999). These treatments are often used in conjunction with care provided by conventional (allopathic) health care providers, but not necessarily with the provider's knowledge (Astin et al., 1998; Knaudt et al., 1999). Systematic evaluation of the effects of CAM for diagnosed mental disorders has been very limited. St. Johns' wort (Hypericum perforatum), an herbal product widely used for its moodelevating properties, is arguably the most extensively investigated CAM therapy. However, evidence to support its use remains inconsistent and confusing (Linde, Mulrow, Berner, & Effer, 2005). By comparison, very few randomized controlled trials (RCTs) have been performed in patients with anxiety disorders meeting criteria from the current Diagnostic and Statistical Manual of Mental Disorders (DSM) (American Psychiatric Association, 2000) or (p. 452) International Classification of Diseases (ICD) (World Health Organization, 1993). Most published works have focused on other clinical populations (e.g., cancer, pre- and postoperative patients, wound-healing, chronic neurologic disorders) and situational anxiety in healthy controls. In this chapter, the authors summarize findings from systematic investigations of CAM in treating anxiety disorders and other anxiety states.

Biologically Based Practices

Biologically based practices are part of an ancient healing tradition dating back to prehistoric times. For example, medicinal herbs were found among the personal effects of the mummified Ice Man discovered in Italy in 1991. Practices included under this rubric are noted in Table 1. Among U.S. adults, the most widely used dietary supplements are botanical products, with two products purported to have psychotropic effects among the top 10 products used in 2002: ginkgo biloba (21%) for cognitive enhancement and St. John's wort (12%) for depression (Barnes et al., 2004).

Botanicals

Kava (Piper methysticum) has been used for centuries in South Pacific cultures as a tranquilizing agent and has been adopted in Western Europe for the treatment of anxiety and nervous tension. Findings from preclinical models suggest anxiolytic effects may be mediated through several neurotransmitter systems (e.g., GABA, serotonin, norepinephrine, and dopamine) (Baum, Hill, & Rommelspacher, 1998; Jossofie, Schmiz, & Hiemke, 1994; Seitz, Schule, & Gleitz, 1997). A 2005 Cochrane Database review found that, compared with placebo, kava was an effective symptomatic short-term treatment (1–24 weeks) for anxiety, with the caveats that (1) the effect was small, (2) there were only a few studies with small sample sizes, and (3) rigorous trials with large samples are needed to further clarify efficacy and safety issues (Pittler & Ernst, 2002). Further examination of the individual studies reveals samples of patients with a broad diagnostic representation, ranging from generalized anxiety disorder (GAD; DSM-IV) to nonpsychotic anxiety (DSM-III-R) to a variety of situationally bound anxiety states. Findings from subsequent reports have been inconsistent; a meta-analysis of 6 randomized controlled trials (RCTs) using the same kava product in adults with nonpsychotic anxiety suggested an effect for kava (Witte, Loew, & Gaus, 2005), while results from a pooled analysis of 3 RCTs using the same product in adults with DSM-IV GAD failed to find any significant clinical effects for kava (Connor, Payne, & Davidson, 2006). While it is possible that kava may be of benefit in milder stress reactions, one must carefully examine the risk-benefit ratio of treating with kava. Given the concerns raised in recent years regarding potential hepatotoxicity with the product (Stikel et al., 2003), at the present time, it is hard to justify kava's use in clinical psychiatry.

Table 1. Commonly Used Complementary and Alternative Medicine Therapies

Biologically based practices: botanicals, animal-derived extracts, vitamins, minerals, fatty acids, amino acids, proteins, prebiotics and probiotics, whole diets, and functional foods

Manipulative and body-based practices: chiropractic and osteopathic manipulation, massage therapies, reflexology

Mind-body intervention strategies: relaxation, hypnosis, visual imagery, meditation, yoga, biofeedback, tai chi, qi gong

Energy medicine: deals with two type of energy fields:

(1) veritable (involves use of specific, measurable wavelengths and frequencies to treat patients), and

(2) putative (fields that have defied reproducible measurement to date; also called biofields)

Whole medical systems: traditional Chinese medicine, Ayurvedic medicine, naturopathy, homeopathy

Valerian (Valeriana officinalis) has been traditionally used as a hypnotic for mild to moderate subjective complaints of insomnia. Valerian contains a number of constituents that have demonstrated central nervous system (CNS) activity, and proposed mechanisms include activity at melatonin, serotonin, and central adenosine receptors, as well as through the inhibitory neurotransmitter GABA (Abourashed, Koetter, & Brattshrom, 2004; Schellenberg, Sauer, Abourashed, Koetter, & Brattsrom, 2004). Systematic data supporting possible anxiolytic effects are scant. In one RCT of 36 patients with DSM-III-R GAD treated with valerian extract (81.3 mg/day), diazepam (6.5 mg/day), or placebo for 4 weeks, no differences were noted between any of the treatments on the primary anxiety outcome measures (Andreatini, Sartori, Seabra, & Leite, 2002). The anxiolytic effect of three single doses of valerian in combination with lemon balm (Mellisa officinalis) was assessed in a placebo-controlled (p. 453) crossover study in 24 healthy adults subjected to stress in a laboratory setting. Mixed anxiolytic effects were observed, with greater effect at the lowest dose (600 mg), but reduced cognitive performance at all doses (Kennedy, Little, Haskell, & Scholey, 2006).

Other Supplements

Little research exists on the anxiolytic effects of vitamins, minerals, and other dietary supplements. Gotu kola (Centella asiatica) has been associated with significant reduction in acoustic startle response in healthy adults, but the effect in patients with clinically significant anxiety is unknown (Bradwejn, Zhou, Koszycki, & Jakov, 2000). One RCT assessed the effect of a multivitamin combination containing calcium, magnesium, and zinc, on psychological well-being in 80 healthy adult males (Carroll, Ring, Suter, & Willemsen, 2000). After 1 month of treatment, the multivitamin combination was superior to placebo in reducing anxiety and perceived stress, suggesting a possible stress-modulating effect for the supplement. While this treatment demonstrated an effect in healthy adults without clinically significant anxiety, the effect in patients with clinically significant anxiety is unknown. Omega-3 fatty acids are popular nutritional supplements that may also have a role in treating anxiety, as suggested by positive findings from open-label studies in test anxiety (Yehuda, Robinovitz, & Mostofsky, 2005) and DSM-IV anxiety disorders (Connor, Zhang, Watkins, Payne, & Davidson, 2005). However, larger, well-designed RCTs are needed to further understand the possible role for omega-3 fatty acids in treating anxiety.

Manipulative and Body-Based Practices

Manipulative and body-based practices focus primarily on structures and systems of the body, including bones, joints, soft tissues, and the circulatory and lymphatic systems. Some of these practices are integral components of ancient, traditional medical systems (e.g., traditional Chinese medicine, ayurveda), while others were developed within the last 150 years (chiropractic and osteopathic manipulation). While quite different in many respects, these practices share the following principles: the human body is self-regulating and has the ability to heal itself; and the parts of the human body are interdependent. It is notable that these modalities are among the most common CAM approaches used by mainstream physicians in the United States (Astin et al., 1998).

Chiropractic

Chiropractic focuses on the relationship between the body's structure (particularly the spine) and function. Practitioners use hands-on therapy (called manipulation or adjustment), which often involves rapid movements and is in contrast to some other body-based treatments. The conceptual basis of chiropractic care is that misalignments of the spine interfere with “nerve flow” and lead to disease.

Chiropractic is growing in popularity among suffers of chronic back pain, who tend to perceive the therapy as a valuable component of their health care. Despite this public endorsement, conclusions from systematic assessments provide guarded optimism in chiropractic's role in treating acute lower back pain, neck pain, and muscle tension headaches (Kaptchuk & Eisenberg, 1998). It is notable that these pain syndromes are common in anxiety patients and, while chiropractic has not been studied in an RCT of patients with anxiety disorders, improvement in pain may lead to an indirect reduction in anxiety. One RCT has examined the effect of chiropractic on blood pressure and anxiety, finding reduction in blood pressure, but no difference from placebo on its effect on anxiety (Yates, Lampling, Abram, & Wright, 1988).

Massage

The anxiolytic effects of massage have been investigated in a variety of clinical populations, including women in labor, women with premenstrual dysphoric disorder, patients with subacute lower back pain, poststroke, and prior to surgery. Administered either in a single session or multiple sessions over days or weeks, in comparison to placebo, the benefits were generally noted immediately after treatment (Agarwal et al., 2005; Chang, Wang, & Chen, 2002; Mok & Woo, 2004), although in two trials the differences were noted at follow-up (Preyde, 2000) or at various time points in the study (Hernandez-Reif et al., 2000). Factors that likely contribute to these inconsistencies include the differences in study samples, massage therapy techniques, duration of treatment (single versus multiple treatments), and other study design features.

Massage may also be used in combination with aromatherapy. A meta-analysis of this treatment combination in different populations revealed an effect size comparable to psychotherapy in reducing trait anxiety (Moyer, Rounds, & Hannum, 2004). In a systematic review of lung cancer patients receiving combined massage and aromatherapy, reduction in anxiety was the most consistent clinical finding (p. 454) (Fellowes, Barnes, & Wilkinson, 2004). While its effect in anxiety disorders is unknown, massage with or without aromatherapy may be of particular benefit for reducing anxiety in patients at risk for poor medication tolerability and/or drug-drug interactions, or in whom conventional therapies have provided limited relief.

Mind-Body Intervention Strategies

Mind-body medicine has been defined as “interventions that use a variety of techniques designed to facilitate the mind's capacity to affect bodily function and symptoms” (Astin, Sharpiro, Eisenberg, & Forys, 2003), and largely focuses on strategies and interventions to promote health. Fundamental precepts include the respect for and enhancement of an individual's capacity for self-knowledge and selfcare. Illness is viewed as an opportunity for growth and transformation, with health care providers serving as guides or catalysts in this process. As with other CAM modalities, many of these approaches are components of ancient healing traditions. Yet today, mind-body interventions constitute a large portion of CAM use, with more than 30% of U.S. adults reporting use of relaxation techniques and imagery, biofeedback, and hypnosis in 2002 (Wolsko, Eisenberg, Davis, & Phillips, 2004).

Research in recent decades has empirically demonstrated the physiologic relationship between stress and neuroendocrine responses in animals, with the attribution of the phrase fight or flight to describe sympathetic nervous system activation to perceived stress (Cannon, 1932). In humans, mind-body interventions attempt to modify this stress response by reducing sympathetic activation and increasing parasympathetic tone. Examples of treatments in this field include relaxation, hypnosis, meditation, biofeedback, music, aromatherapy, yoga, tai chi, and qi gong. While several of these areas will be discussed below, additional information on meditation-based treatments can be found in Chapter 36.

Hypnosis

Hypnosis is an altered state of consciousness where a hypnotherapist can increase the patient's attention and make the patient more responsive to suggestions. Advocates compare the trancelike state of awareness in hypnosis to the experience of being so intensely focused on a task that one becomes unaware of things in the surrounding environment. Hypnosis may involve the therapist inducing a relaxed state by talking in a way that creates a sense of relaxation and security. The therapist may also help create visual imagery or, alternatively, teach techniques of self-hypnosis.

The putative mechanism of action for the hypnotic effect is unknown, but it may involve activation of medial prefrontal cortex and left dorsolateral prefrontal cortex, thus affecting information processing (Linden, 2006). There is mixed evidence for efficacy of hypnosis in anxiety. An RCT in patients with acute stress disorder demonstrated that hypnosis in conjunction with cognitive behavioral therapy (CBT) is more effective than either CBT or supportive counseling alone (Bryant, Moulds, Guthrie, & Nixon, 2005). However, a systematic review of a form of hypnosis (autogenic training) for stress and anxiety was inconclusive due to the poor methodological quality of the trials (Ernst & Kanji, 2000).

Biofeedback

Biofeedback techniques help patients to control involuntary body responses (e.g., blood pressure, muscle tension, heart rate, or even neural activity) (DeCharms et al., 2005). Treatment sessions involve measuring the patient's physiological responses, with the therapist providing feedback via auditory and visual cues. Over time, the patient associates the physiological response with the symptom, and applies various techniques to reduce these responses (Manuck, 1976). The mechanism of action is not entirely known, although it is hypothesized that so-called autonomic functions (that were thought to be entirely automatic) are under conscious control to some extent. It is noteworthy that some patients with stress-responsive conditions (i.e., hypertension, diabetes) who apply biofeedback skills may experience improvement in their conditions and require lower doses of medication.

With regard to effects on anxiety, findings from one RCT in patients with GAD showed that after 8 sessions, biofeedback significantly reduced state anxiety and physiologic symptoms, with maintenance of effect 6 weeks after treatment (Rice, Blanchard, & Purcell, 1993). A similar finding occurred with alcohol-dependent patients with high anxiety (Clark & Hirschman, 1990).

Music

The therapeutic effects of music have been demonstrated not only through subjective reports of relaxation, but also through observed entrainment of motor and sensory functions that have facilitated recovery in patients with neurologic dysfunction (e.g., cerebral palsy, stroke, traumatic brain injury). While the putative mechanism of action is (p. 455) unknown, evidence suggests that music affects the release of norepinephrine and corticotropin releasing hormone (CRH) (Watkins, 1997).

Evidence supporting the effectiveness of music therapy to treat anxiety is inconclusive. A meta-analysis found music reduces anxiety in hospital patients undergoing normal care, but not in preoperative patients (Evans, 2002). However, a systematic review of the effect of music therapy on anxiety experienced by patients in short-term waiting periods, such as day surgery, was inconclusive (Cooke, Chaboyer, & Hiratos, 2005).

Aromatherapy

Aromatherapy utilizes the application of aromatic oils for therapeutic benefit and is often combined with massage. While the mechanism of action is unknown, there is some evidence to suggest effects on neurotransmitters and perhaps even neuroprotective effects (Perry & Perry, 2006).

In terms of an effect on anxiety, results are mixed. Following a systematic review, Cooke and Ernst 2000 concluded that aromatherapy has mild, transient anxiolytic effects. Three subsequent controlled trials found that aromatherapy was not effective in reducing anxiety in patients with advanced cancer after 4 weeks (Soden, Vincent, Crasken, Lucas, & Ashley, 2004), or in patients receiving radiation therapy (Graham, Browne, Cox, & Graham, 2003), or prior to therapeutic abortion (Wiebe, 2000). However, in a trial of 40 healthy adults, aromatherapy with lavender (considered a relaxing scent) compared to rosemary (considered a stimulating scent) was associated with reduction in anxiety and related EEG changes (Diego et al., 1998). In addition, in patients undergoing magnetic resonance imaging (MRI) testing for a diagnostic cancer workup, aromatherapy was associated with reduced anxiety (Redd, Manne, Peters, Jacobsen, & Schmidt, 1994).

Yoga

Yoga is an ancient practice from India that literally means to yoke, the concept being that yoga helps yoke or bind together one's physical, mental, and spiritual dimensions. Yoga incorporates various specific postures to increase the flow of life energy (or prana in Sanskrit).

In a systematic review of studies of yoga for anxiety, each of the 8 studies meeting selection criteria (8 controlled trials; 6 were randomized and 2 were not) showed a positive result in favor of yoga. The most methodologically rigorous study provided a positive result as well; of note, a meta-analysis could not be performed because of study heterogeneity, mainly because of the varied conditions studied (Kirkwood, Rampes, Tuffrey, Richardson, & Pilkington, 2005). A subsequent Cochrane Database review was inconclusive; it selected two studies for inclusion, one in which transcendental meditation (TM) reduced anxiety symptoms and electromyography scores comparable with electromyography-biofeedback and relaxation therapy, while the other showed that Kundalini Yoga (KY) did not differentiate from relaxation/mindfulness meditation in lowering anxiety (Krisanaprakornkit, Krisanaprakornkit, Piyavhatkul, & Laopaiboon, 2006). Likely the most rigorous RCT on yoga in the literature compared KY with a relaxation response and mindfulness meditation arm in obsessive-compulsive disorder (OCD) patients and found a significant treatment difference in favor of KY, with a large effect size of 1.10 (Shannahoff-Khalsa et al., 1999).

Less rigorous trials have shown a mixed picture. In other trials examining the effects of a variety of yoga techniques and in which anxiety was not the primary outcome, results have tended to be negative, including in patients with multiple sclerosis (Iyengar yoga; Oken et al., 2004), cancer (Tibetan yoga (TY); Cohen, Warneke, Fouladi, Rodriguez, & Chaoul-Reich, 2004), and irritable bowel syndrome (Taneja et al., 2004). Another RCT did find a reduction in anxiety for mildly depressed patients compared to a waitlist control (Woolery, Myers, Sternlieb, & Zeltzer, 2004). In a sample of healthy young adults, one RCT showed decrease in anxiety and increase in parasympathetic activity (Ray et al., 2001). Similarly, yoga has been shown to decrease basal anxiety and anticipatory anxiety in medical students prior to exams (Malathi & Damodaran, 1999).

Energy Medicine

Energy medicine employs the use of veritable and putative energy fields, veritable fields being mechanical or electromagnetic forces that can be measured, and putative fields being fields that have not yet been measurable. The latter is based on the concept that humans have a subtle form of energy known as qi in traditional Chinese medicine, ki in Japan, and prana in Ayurveda.

Energy medicine proponents believe that illness results from disturbances of these subtle energies. Therapeutic approaches in this category include reiki, qi gong, therapeutic touch, and magnetic therapy. The common aspect of all these approaches (p. 456) is that the practitioners believe that by moving their hands over the patient's body, they can reorient the patient's energies. Although there is not currently established physical proof for these subtle energies, a superconducting quantum interference device (SQUID) has been claimed to measure large frequency-pulsing biomagnetic fields emanating from the hands of Therapeutic Touch practitioners during therapy (Zimmerman, 1990).

A systematic review shows some support for therapeutic touch in anxiety/pain (Spence & Olson, 1997). Another review found no generalizable findings (Wardell & Weymouth, 2004). Several RCTs have shown evidence for efficacy; one study showed a trend toward significant reduction of anxiety with therapeutic touch in high anxiety patients (Olson & Sneed, 1995); another showed therapeutic touch and relaxation were significantly beneficial among psychiatric patients with anxiety (Gagne & Toye, 1994); another showed a significant effect of therapeutic touch in reducing anxiety of institutionalized elderly patients (Simington & Laing, 1993); while another study in burn patients showed a significant reduction in anxiety (Turner, Clark, Gauthier, & Williams, 1998). Similarly, therapeutic touch has been shown to reduce anxiety in healthy volunteers (Lafreniere et al., 1999). Magnetic therapy is also considered part of energy medicine; however, no systematic reviews, meta-analyses, or RCTs in anxiety or anxiety disorders have been published to date.

Whole Medical Systems

Whole medical systems include homeopathy, traditional Chinese medicine (TCM), ayurvedic medicine, and chiropractic medicine. These are systems of medicine that are distinguishable from modern Western (allopathic) medicine. They often have their own systems of theory and practice and have evolved separately from Western medicine.

Homeopathy

Homeopathy was developed in Germany and has been practiced in the United States since the early 19th century. One of the key concepts of homeopathy is that patients can heal themselves by invoking their own “vital force.” Practitioners believe that when this vital energy is imbalanced, disease occurs. Homeopathic treatment involves giving very small doses of substances that at larger doses can cause the symptoms that are being treated in order to invoke the patient's own healing powers. Dilution, homeopathy posits, actually makes the treatment more effective by extracting the vital essence of the substance. Homeopathy also posits that treatment must be individualized to the particular patient's emotional and physical state and constitutional type, so that different patients with the same symptoms may necessarily receive different treatments.

No systematic reviews/meta-analyses with homeopathy and anxiety were available. An RCT with GAD patients showed no difference from placebo (Bonne, Shemer, Gorali, Katz, & Shalev, 2003). An animal study showed effects on anxiety in mice with a particular homeopathic preparation (Dhawan, Kumar, & Sharma, 2002).

Traditional Chinese Medicine

Traditional Chinese Medicine (TCM) is a system of healing that dates back more than 2,000 years. The view of TCM is that the body has a balance of two forces, yin (the slow or passive principle) and yang (the fast or active principle). Health, it is believed, is achieved by balancing yin and yang. Imbalance leads to disease by blockage of vital energy (qi) along pathways known as meridians. Herbs, acupuncture, and massage are used to unblock qi.

There were no systematic reviews/meta-analyses available on acupuncture or acupressure with anxiety disorders. Several RCTs have found auricular acupuncture to be effective in reducing anxiety in prehospital transport settings (Kober et al., 2003), in preoperative anxiety in surgical outpatients (Wang, Peloquin, & Kain, 2001), and in healthy anxious adults (Wang & Kain, 2001).

Ayurveda

Ayurveda (or “the science of life”) is a system of healing from ancient India that places emphasis on balancing mind, body, and spirit. Ayurvedic treatments include diet, massage, use of herbs and metals, exercise, meditation, and yoga. Meditation is covered elsewhere in this chapter and yoga has been discussed earlier. Two ayurvedic herbs have activity to suggest potential anxiolytic effects: Sesbania grandiflora, traditionally used to treat so-called epileptic fits; and Withania somnifera, used to promote physical and mental health and to defend against disease and adverse environmental influences. In mice, treatment with the leaves of S. garndiflora was associated with increased brain levels of GABA and serotonin and with greater time in the open arm of the elevated plus maze, indicating anxiolytic activity (Kasture, Deshmukh, & Chopde, 2002). The roots of W. somnifera contain bioactive glycowithanolides (WSG) which, in rats, have shown anxiolytic (p. 457) activity comparable to lorazepam in several models for anxiety as well as in reduction of brain levels of tribulin, an endocoid marker of clinical anxiety, following administration of an anxiogenic agent (pentylenetetrazole) (Bhattacharya, Bhattacharya, Sairam, & Ghosal, 2000). However, while evidence from animal models suggests anxiolytic activity for these herbs, these effects have not been investigated in humans.

Summary and Conclusions

Complementary and alternative medicine practices have immense popularity, although upon critical investigation, many of these practices often do not stand up to scientific scrutiny. Botanical products in particular have to be taken with caution as they do not undergo the same regulatory scrutiny as medications. Drug products undergo rigorous investigation and regulatory review for evidence of efficacy and safety prior to being approved for use in the market. Manufacturers are also required to follow good manufacturing practices (GMP) and any claims of benefit must be submitted to regulatory authorities for review and approval. Different regulatory requirements, however, are applied to dietary supplements, including botanical products. For example, in the United States, supplements are regulated as food products by the Food and Drug Administration (FDA), under the guidance of the Dietary Supplement Health and Education Act (DSHEA) of 1994, and are subject to the same GMP standards of foods, but not of drugs. Manufacturers of supplements are responsible for ensuring the safety of their products and are not subject to premarket approval or a specific postmarketing surveillance period by the FDA. Under DSHEA, manufacturers may make claims of benefit based on the published literature, and the Federal Trade Commission is then responsible for monitoring manufactured products for truth in advertising. This regulatory framework is under review in the United States and, in examining the safety of supplements in 2002, the Institute of Medicine issued a report recommending a framework for the cost-effective and science-based evaluation of supplements by the FDA (Institute of Medicine of the National Academies, 2004).

Given these differences, there are a number of issues to consider when interpreting data from studies of supplements, and for botanical products in particular. Medicinal herbs are complex mixtures of a variety of potentially pharmacologically active compounds, with potentially multiple actions. Herbs are also available in a variety of forms (e.g., fresh, dried, extracts), using different plant parts (e.g., roots, leaves, flowers), and routes of administration (e.g., pills, ointments, oils, suppositories, inhaled smoke, infused beverages). The content of active constituents in a given botanical product varies depending on a number of variables, including the plant part used, growing conditions, procedures used for collection, storage, processing, and stability over time. Thus, there are high levels of inter-batch and interproduct variability. Traditionally, these treatments have been used in the restoration of health, whereas drugs are generally designed to affect a specific ailment or disease. Therefore, one could question if the current gold-standard RCT model is appropriate to assess the efficacy of these treatments. Lastly, readers need to consider issues of study methodology when interpreting study results, including but not limited to the following: diagnostic heterogeneity of samples; small sample sizes; variability in products, doses, route of administration, and duration of treatment; adequacy of placebo controls, blinding, and comparators; and use of validated outcome measures.

Despite the lack of scientific evidence to support efficacy and safety in combining CAM with conventional medical treatment, more than half of U.S. adults use CAM for this purpose, believing that this combination will improve their health (Barnes et al., 2004). We know that botanical products are commonly used in this manner and that patients are often reluctant to disclose this use to their health care providers. Therefore, it is the responsibility of health care providers to inquire about use of dietary supplements in all patients at each visit. While very little is known about supplement-medicine and supplement-supplement interactions, several serious interactions have been reported, such as those between St. John's wort and immunosuppressants or antiretrovirals (Izzo, 2004).

In conclusion, systematic research on CAM modalities in anxiety disorders is very limited and has yielded results that are often inconclusive. Given the popularity of CAM worldwide, further research is needed to increase our understanding of the safety and efficacy of these approaches. In addition, it is imperative that health care providers be mindful of patients' use of these therapies and discuss the use of supplements and other CAM treatments with their patients.

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