Complementary and Alternative Medicine Use for Treatment and Prevention of Late-Life Mood Disorders

Trends in the Use of CAM in the United States

The use of complementary and alternative medicine (CAM) in the United States is increasing rapidly, exceeding a prevalence of 60% in a nationally representative survey conducted by the National Center for Health Statistics in 2002.^1,2 CAM therapies are defined by the National Center for Complementary and Alternative Medicine as a group of diverse medical and health systems, practices, and products that are not currently considered to be part of conventional medicine.³ An alternative approach to mental health care is one that emphasizes the interrelationship between mind, body, and spirit. A national U.S. survey noted a 47% increase in total visits to CAM practitioners, from 427 million in 1990 to 629 million in 1997.³ Estimated expenditures for CAM professional services were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion of out-of-pocket expenditures, exceeding out-of-pocket expenditures for all U.S. hospitalizations.³ In a more recent nationwide survey, 36% of U.S. adults age 18 years and older use some form of CAM, and aging baby boomers are expected to accelerate the use of CAM in the coming years.⁴

Despite the increasing use of CAM by individuals, the scientific support for its efficacy is limited. The treatments with the best evidence of effectiveness are St. John’s wort, exercise, and light therapy (for seasonal depression). There is only some degree of evidence to support the effectiveness of acupuncture, light therapy (for nonseasonal depression), massage therapy, negative air ionization (for winter depression), relaxation therapy, S-adenosyl-L-methionine, folate, and yoga breathing exercises.⁵

Use of CAM therapies is typically associated with higher levels of education, poorer health status, environmentalism, feminism, and interest in spirituality and personal growth psychology.⁶ Barnes and colleagues⁴ noted that nearly 33% of older adults used CAM in the preceding year. In their survey, 42% of the patients in a managed care organization reported using at least one CAM therapy, most commonly relaxation techniques (18%), massage (12%), herbal medicine (10%), or megavitamin therapy (9%).⁴

This review is devoted to the description of the evidence-based CAM treatments applied to the care of older adults with late-life mood disorders (Table). We will discuss some of the more commonly used interventions.

Use of CAM in Late-Life Mood Disorders

Mood disorders are the most frequently occurring psychiatric syndromes in older adults. Depressive symptoms occur in approximately 10-15% of patients in primary care settings. The prevention and treatment of depression are important areas to define: depression is linked to cognitive decline and is considered to cause a worldwide health burden greater than that of ischemic heart disease, cerebrovascular disease, or tuberculosis.

Mood disturbances are commonly observed in patients with neurodegenerative disorders including probable Alzheimer’s disease (AD), Parkinson’s disease (PD), and post-stroke depression. Clinically, preference is given to therapy with antidepressants that do not have a significant anticholinergic effect. Other treatment strategies include treatment of pain and infection, environmental and behavioral management, and professional caregiver training. Despite rigorous research, the response to these therapies remains only modest and partial for most patients. While CAM treatments are widely used by consumers, very little research is available to guide patients and their caregivers—or even practitioners in the field. The perceived helpfulness of CAM therapies is similar to that of conventional therapies.^2,5

St. John’s Wort (Hypericum perforatum)
St. John’s wort has been extensively studied in Europe, particularly in Germany. A recent meta-analysis of 23 randomized trials (20 were double-blind) in a total of 1757 outpatients with mild-to-moderate depression found improvement in depressive symptoms in all groups.² In 15 placebo-controlled studies, medication was more effective than placebo. In eight treatment-controlled trials, St. John’s wort was as effective as tricyclic antidepressants (TCAs). However, a recent large National Institutes of Health–sponsored U.S. multisite, randomized trial of St. John’s wort compared to sertraline and placebo for treatment of major depression failed to find drug-placebo differences.⁷

A recent Cochrane database review provided the analyses total of 37 trials, including 26 comparisons with placebo and 14 comparisons with synthetic standard antidepressants.⁸ Results of placebo-controlled trials showed marked heterogeneity. In trials restricted to patients with major depression, the combined response rate ratio (RR) for hypericum extracts as compared with placebo from six larger trials was 1.15 (95% confidence interval [CI], 1.02-1.29) and from six smaller trials was 2.06 (95% CI, 1.65-2.59). In trials not restricted to patients with major depression, the RR from six larger trials was 1.71 (95% CI, 1.40-2.09) and from five smaller trials was 6.13 (95% CI, 3.63-10.38). Trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. As compared with selective serotonin reuptake inhibitors (SSRIs) and TCAs or tetracyclic antidepressants, respectively, RRs were 0.98 (95% CI, 0.85-1.12; 6 trials) and 1.03 (95% CI, 0.93-1.14; 7 trials). Patients who were given hypericum extracts dropped out of trials due to adverse effects less frequently than those who were given older antidepressants (odds ratio [OR], 0.25; 95% CI, 0.14-0.45); such comparisons were in the same direction, but not statistically significantly different, between hypericum extracts and SSRIs (OR, 0.60; 95% CI, 0.31-1.15).

Therefore, current evidence regarding hypericum extracts is inconsistent and confusing. In patients who meet the criteria for major depression, several recent placebo-controlled trials suggest that the tested hypericum extracts have minimal beneficial effects, while other trials suggest that hypericum and standard antidepressants have similar beneficial effects. The recommended doses include 300 mg three times daily or 450 mg twice daily. As the preparations available on the market might vary considerably in their pharmaceutical quality, the results of this review apply only to the products tested in the included studies.

Although it is commonly believed that herbal preparations are safer than the synthetic ones, many of them have limiting side effects. St. John’s wort is useful for the treatment of mild-to-moderate depression but has multiple potentially dangerous and lethal drug interactions due to its monoamine oxidase inhibition demonstrated in vitro.^7-9 In addition, concurrent use of drugs metabolized by means of the cytochrome CYP-450 liver enzyme system may result in altered therapeutic levels because of induction or inhibition of enzymes by St. John’s wort that might preclude its use in elderly persons taking multiple medications, due to potential drug interactions. Human pharmacokinetic studies have reported induction of CYP 3A/3A4 by reductions of drug concentrations. The drug levels of such medications as carbamazepine, cyclosporine, estrogens and oral contraceptives, as well as statins may be altered, causing potentially dangerous and life-threatening side effects. A significant decrease in cyclosporine levels in transplant recipients (eg, kidney, heart) taking St. John’s wort may result in acute transplant rejection and death.¹⁰

In summary, the use of St. John’s wort can be reserved for mild-to-moderate depression in individuals who prefer the use of “natural” remedies and are opposed to the use of antidepressants or psychotherapy. Patients will have to be informed about potential side effects and drug interaction.

Omega-3 Fatty Acids
Other common dietary supplements are fish oil and omega-3 fatty acids. Reductions in cardiovascular risk, depression, and rheumatoid arthritis symptoms have been correlated with omega-3 fatty acid intake, and there is increased interest in the use of omega-3 fatty acid supplementation for other psychiatric illnesses and prevention of AD. Omega-3 fatty acids are found principally in fish and other seafood, although some can be derived from green vegetables. By contrast, omega-6 fatty acids are found in soft margarine, most vegetable oils, and animal fat. Omega-6 is plentiful in most modern Western diets, while omega-3 is often relatively lacking. A high dietary ratio of omega-6 to omega-3 has been linked to vulnerability to many physical and mental disorders. Reported health benefits of omega-3 fatty acids include improvements in mood in unipolar and bipolar disorders, as well as dementia.^5,11-13

There is mounting evidence that dietary supplementation with omega-3 fatty acids may be beneficial in treating a variety of conditions including several psychiatric disorders,¹³ although not all studies are in agreement. Most studies recommend omega-3 essential fatty acids with an EPA:DHA (eicosapentaenoic acid:docosahexaenoic acid) ratio of 7:1. In a recent trial, supplementation with omega-3 in patients with mild-to-moderate AD did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms and agitation symptoms.¹⁴

In summary, omega-3 fatty acids may have a role in the treatment of late-life neuropsychiatric disorders; however, additional studies are needed before their use can be recommended confidently to patients.

S-adenosyl-L-methionine 
S-adenosyl-L-methionine (SAMe) is one of the CAM products that has been studied under rigorous controlled conditions. SAMe is derived from the amino acid L-methionine through the one-carbon cycle, and it is a methyl donor involved in the synthesis of the monoaminergic neurotransmitters. SAMe has been investigated for its antidepressant properties in both open¹¹ and randomized controlled trials.¹⁵ SAMe dosages of 200-1600 mg/day (orally or parenterally) have been shown to be superior to placebo and as effective as TCAs in alleviating depression, although some individuals may require higher doses.¹⁵ SAMe may have a faster onset of action than conventional antidepressants and may potentiate the effect of TCAs¹⁵ or SSRIs. At this time, the recommended dose range most commonly used includes SAMe 200 mg twice daily up to 800 mg twice daily. Oral dosages of SAMe up to 1600 mg/day appear to be significantly bioavailable and safe. SAMe has been associated with minor adverse effects (eg, gastrointestinal symptoms, headaches). However, as with any antidepressant compound, some cases of mania have been reported in patients with bipolar disorder taking SAMe.¹⁵

Overall, SAMe appears to be safe and efficacious in the treatment of depression, but further controlled studies are indicated because current evidence comes mostly from open trials or small controlled studies. SAMe may have a role in the management of patients with bipolar disorder, but more research is needed, in particular to determine its effective dose and to better assess the risk of switch to mania or hypomania.¹⁵ In addition, more research should be conducted on the role of these and other natural products in the prevention and treatment of psychiatric symptoms.

Acupuncture
The Chinese practice of inserting needles into the body at specific points manipulates the body’s flow of energy to balance the endocrine system. This manipulation regulates functions such as heart rate, body temperature, and respiration, as well as sleep patterns and emotional changes. Acupuncture has been used in clinics to assist people with substance abuse disorders through detoxification, to relieve stress and anxiety, to treat attention-deficit hyperactivity disorder in children, to reduce symptoms of depression, and to help people with physical ailments. As compared to other empirically validated treatments, acupuncture designed specifically to treat major depression produced results that are comparable in terms of rates of response and of relapse or recurrence. In a recent small study of acupuncture, positive subjective and objective effects were found on mood and well-being.¹⁶ However, in the recent Cochrane database review of seven trials comprising 517 subjects who generally had mild-to-moderate depression, there was no evidence that medication was better than acupuncture in reducing the severity of depression or in achieving remission.¹⁷ These results warrant a larger trial of acupuncture in the acute- and maintenance-phase treatment of depression.

Ayurveda
Ayurveda is a comprehensive natural healthcare system that originated in India more than 5000 years ago and has been used for anti-aging, memory-enhancement, nerve tonic, anxiolytic, anti-inflammatory, and immunopotentive remedies. It is still widely used in India as a system of primary healthcare, and interest is growing worldwide as well. Ayurveda means “the science of life.” Ayur means “life” and veda means “knowledge or science.” Ayurvedic medicine is described as “knowledge of how to live.” It incorporates an individualized regimen such as diet, meditation, herbal preparations, or other techniques to treat a variety of conditions including depression to facilitate lifestyle changes and to teach people how to release stress and tension through yoga or transcendental meditation. There are encouraging results for its effectiveness in treating various ailments, including chronic disorders associated with the aging process. Pilot studies of depression, anxiety, sleep disorders, hypertension, diabetes mellitus, PD, and AD have yielded positive results.¹⁸

Mindful Physical Exercise and Meditation
Mindful physical exercise (eg, yoga, qigong, tai chi) is a special kind of physical exercise with an additional element that focuses on one’s state of mind. It has recently emerged as a therapeutic intervention for improving the psychosocial well-being of individuals. According to the IDEA Mind–Body Fitness Committee (1997-2001), mindful physical exercise is characterized by “physical exercise executed with a profound inwardly directed contemplative focus.” A physical exercise is considered mindful if it: (a) has a meditative/contemplative component that is noncompetitive and nonjudgmental; (b) has proprioceptive awareness that involves a low to moderate level of muscular activity with mental focus on muscular movement; (c) is breath centering; (d) focuses on anatomic alignment, such as spine, trunk, and pelvis, or proper physical form; and (e) involves energy centric as awareness of individuals’ flow of intrinsic energy, vital life force, qi, etc.

With the above framework, yoga and qigong are two major streams of mindful physical exercise based on the literature. Yoga is used in combination with other treatments for depression, anxiety, and stress-related disorders. Practitioners of yoga, the ancient Indian system of healthcare, use breathing exercises, posture, stretching, and meditation to balance the body’s energy centers. Qigong is a Chinese meditative practice that often uses slow, graceful movements and controlled breathing techniques to promote circulation of qi within the body.

Mindful physical exercise has been shown to provide an immediate source of relaxation and mental quiescence. Scientific evidence shows that medical conditions such as hypertension, cardiovascular disease, insulin resistance, depression, and anxiety disorders respond favorably to the mindful physical exercises.¹⁹ The effects of yoga and Ayurveda on geriatric depression were evaluated in 69 persons older than age 60 who were living in a residential home.²⁰ The depression symptom scores of the yoga group at both 3 and 6 months decreased significantly, from a group average baseline of 10.6 to 8.1 and 6.7, respectively (P < 0.001, paired t-test). The other groups showed no change. Hence, an integrated approach of yoga, including the mental and philosophical aspects in addition to the physical practices, was useful for institutionalized older persons.

Clinical effects of meditation impact a broad spectrum of physical and psychological symptoms and syndromes, including reduced anxiety, pain, and depression, enhanced mood and self-esteem, and decreased stress. Meditation has been studied in populations with fibromyalgia, cancer, hypertension, and psoriasis. Meditation practice can positively influence the experience of chronic illness and can serve as a primary, secondary, and/or tertiary prevention strategy. Healthcare professionals demonstrate commitment to holistic practice by asking patients about use of meditation, and they can encourage this self-care activity. Simple techniques for mindfulness can be taught in the clinical setting. Living mindfully with chronic illness is a fruitful area for research, and it can be predicted that evidence will grow to support the role of consciousness in the human experience of disease.

Spirituality and Pastoral Care
Some people prefer to seek help for mental health problems from their pastor, rabbi, priest, or other religious leader, rather than from therapists who are not affiliated with a religious community. Counselors working within traditional faith communities increasingly are recognizing the need to incorporate psychotherapy and/or medication along with prayer and spirituality to effectively help some people with mental disorders. While religiousness and social support have been shown to influence depression outcome, some researchers have theorized that religiousness largely reflects social support. In a study by Bosworth et al,²¹ religious coping was related to social support but was independently related to depression outcome. The authors concluded that clinicians caring for older patients with depression should consider inquiring about spirituality and religious coping as a way of improving depressive outcomes.²¹ The protective effects of religion against late-life depression may depend on the broader sociocultural environment. Religious practice, church attendance, or prayer, especially when it is embedded within a traditional value orientation, may facilitate coping with adversity in later life and stress reduction.²²

Addressing spirituality in the clinical encounter may lead to improved detection of depression and treatments that are more congruent with a patient’s beliefs and values, as shown in the study of older African-American participants who described depression as being due to a “loss of faith”; faith and spiritual/religious activities were thought to be empowering in the way that they can work together with medical treatments to provide the strength for healing to occur.²³ Faith-based intervention can improve the outcomes of treatment as shown in using the “Christian Steps to Freedom” model prayers, used by individual patients personally and/or with a counselor, that reduced their psychiatric symptoms as compared to those who did not practice prayer.²⁴

Exercise
Human and other animal studies demonstrate that exercise targets many aspects of brain function, providing broad effects on overall brain health. The benefits of exercise have been best defined for learning and memory, protection from neurodegeneration, and alleviation of depression, particularly in elderly populations. Exercise increases synaptic plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by strengthening the underlying systems that support plasticity, including neurogenesis, metabolism, and vascular function. Such exercise-induced structural and functional change has been documented in various brain regions but has been best studied in the hippocampus.²⁵

Emerging evidence suggests that exercise has therapeutic and preventive effects on depression.²⁵ Therapeutic effects of exercise on depression have been most clearly established in human studies. Randomized and crossover clinical trials demonstrate the efficacy of aerobic or resistance training exercise (2-4 mo) as a treatment for depression in both young and older individuals.^26,27 The benefits are similar to those achieved with antidepressants.²⁶ They are also dose-dependent: greater improvements are seen with higher levels of exercise.²⁷

Although exercise seems to have both preventive and therapeutic effects on the course of depression, the underlying mechanisms are poorly understood. Protective effects of exercise from stress have focused on the hippocampus, where exercise-induced neurogenesis and growth factor expression have been proposed as potential mediators, although not without controversy. Other proposed mechanisms include exercise-driven changes in the hypothalamic–pituitary–adrenal axis that regulates the stress response, and altered activity of dorsal raphe serotonin neurons implicated in mediating learned helplessness behaviors.

Expressive Therapies
Creativity interventions have been shown to positively affect mental and physiological health indicators in older adults. Developing creative coping strategies can enable older adults to adapt more effectively to physical, psychological, and psychosocial changes that occur during old age. The process of creating and one’s attitude toward life may be more important than the actual product or tangible outcome. Late-life creativity reflects aspects of late-life thinking: synthesis; reflection; and wisdom. From a problem-solving perspective, creativity is an asset in older adulthood, given the number of health, functional, and financial limitations likely to occur.²⁸ Many older adults might not describe themselves as creative and would be reluctant to engage in typical creative endeavors, such as painting or drawing.

The underlying premise to dance/movement therapy is that it can help a person integrate the emotional, physical, and cognitive facets of “self.” A recent study designed a multimodal program aimed at influencing a group of 75 older adult participants’ purpose in life, depression, and hypochondriasis by targeting physical, mental, and spiritual well-being.²⁹ Interventions included: rhythm and dance exercises; general physical exercises; recreational exercise outdoors; relaxation exercises; a creativity enhancement seminar; a seminar on psychology and philosophy of life; and a seminar on contact with other people and communication. The group sessions were conducted two days per week over a period of four months. Purpose in life, depression, and hypochondria were three parameters of well-being that were measured pre- and post-intervention. The Purpose in Life (PIL) scale measured purpose in life, the Geriatric Depression Scale (GDS) assessed depressive symptoms, and the Hypochondriasis Scale for Institutional Geriatric Patients (HSIG) determined the presence of hypochondria. The first day each week consisted of an hour of some form of exercise and a two-hour seminar. The second day each week was comprised of one hour of relaxation, an hour of exercise, and two hours of a seminar about stimulating creativity. Significant changes in test scores were observed over time. Mean PIL scores increased from pre-intervention to post-intervention, suggesting greater purpose in life, and these scores remained elevated at six months post-intervention. Scores for the GDS and the HSIG decreased from pre-intervention to post-intervention, indicating a decrease in depressive symptoms and hypochondriasis, and continued to be significantly reduced six months post-intervention. Outcomes suggested that interventions were successful in improving quality of life as evidenced by increased purpose in life and decreased depression and hypochondriasis.

Those who prefer more structure or who feel that they have “two left feet” can gain the same sense of release and inner peace from the Eastern martial arts, such as tai chi. There is considerable evidence that tai chi has positive health benefits: physical, psychosocial, and therapeutic.³⁰ Furthermore, tai chi does not only consist of a physical component, but also sociocultural and meditative components that are believed to contribute to overall well-being. Tai chi exercise is chosen by the elderly for its gentle and soft movements. In addition to the physical aspect, the benefits they describe include lifestyle issues, as well as psychological and social benefits.^31,32 Evidence points out that the improvements in physical and mental health through the practice of tai chi among older adults is related to their perceived level of quality of life.³³ It is recommended as a strategy to promote successful cognitive and emotional aging.

Summary

Late-life mood disorders are the most common reasons for using CAM therapies in older persons. The amount of rigorous scientific data to support the efficacy of these therapies in the treatment of depression are extremely limited. There is a need for further research involving randomized controlled trials for the efficacy of CAM therapies in the treatment of depression, cognitive impairment in late-life, and effective treatment approaches for these serious conditions.

Acknowledgment

Dr. Lavretsky’s work was supported by NIH grants R01 MH077650 and R-21 AT003480.

The author reports that she has received research grants from Forest Research Institute.

Dr. Lavretsky is Associate Professor of Psychiatry, Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA.

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