No clinician wants to be a “pill-pusher,” and most of our patients do not want that kind of treatment. So what can we offer our depressed patients beyond medications? In this article, we’ll review the literature on nonpharmacological strategies, including dietary supplements, food recommendations, light therapy, yoga and mindfulness meditation, and exercise. (See Dr. Spielmans’ article, “Psychotherapy for Depression: What’s Best?” in this issue for a review of psychotherapy, and the October 2009 issue of TCPR for a review of medication options for depression.)
Omega-3 Fatty Acids. While omega-3 FAs are likely effective in the treatment of heart disease, the results of clinical trials for mood disorders have been mixed and generally disappointing (Roth EM et al., Curr Atheroscler Rep 2010;12(1):66–72). (For a review, see the February 2010 issue of TCPR.)
Thus far, the FDA has approved only one omega-3 FA preparation, Lovaza, for the treatment of elevated triglyceride levels. It is not approved for any psychiatric indication, but it is being heavily marketed to psychiatrists, presumably in the hopes that they will prescribe it offlabel for mood disorders (or perhaps to treat the increase in triglycerides that some of our medications cause). Each gram of Lovaza contains 375 mg DHA (docosahexaenoic acid) and 465 mg EPA (eicosapentaenoic acid). Most overthecounter preparations of omega-3 FAs contain similar amounts of DHA and EPA, but are much cheaper. The dosage approved to lower triglycerides is four grams of total omega-3 per day, whereas the dosage examined in most psychiatric trials is one to two grams per day.
Is there any reason to prescribe Lovaza to patients rather than recommending an OTC from a reputable manufacturer, such as Nordic Naturals or Nature’s Way? Paradoxically, for some patients Lovaza may be cheaper—that is, if their insurance companies cover most of the cost. However, insurance companies are unlikely to pay for Lovaza unless you are prescribing it for the specific FDA indication of hypertriglyceridemia.
TCPR’s Take: Omega-3 FA supplementation has been shown to be effective for heart health but there is still no convincing evidence that it is effective for mood disorders.
Folic Acid. The relationship between low folate levels and depression is still unclear. There is some support and little risk for recommending folic acid supplementation (400 micrograms/day). However, there is no evidence, other than theoretical, that Deplin (L-methylfolate, an expensive product that is marketed by Pamlab LLC) is more effective than regular folic acid. (For more information, see TCPR’s thorough review of this topic in the June 2009 issue.)
TCPR’s Take: Folate may be an effective adjunctive treatment for depression. We recommend the cheap stuff, meaning basic folic acid that is available for about $3 a month. A list of folate rich foods, which include green leafy vegetables and enriched grains, is available at www.wheatfoods. org. This might be an even better approach for patients.
Vitamin D. A recent epidemiological study suggests that vitamin D deficiency is a risk factor for the development of depression in older persons (Milaneschi Y et al., J of Clinical Endocrinology and Metabolism 2010; online ahead of print). It is also clear that many people are deficient in vitamin D, a deficiency which has been linked to several chronic medical problems (see for example the entire issue of Endocrinol Metab Clin North Am 2010;39(2)). However, there have been no double-blind placebo controlled studies testing vitamin D specifically for depression treatment or prevention.
The Food and Nutrition Board of the National Institutes of Health recommends 200 IU of Vitamin D as a standard “adequate intake” for adults ages 19 to 50, and 400 IU for those 51 to 70. However, recent reports have increased this recommendation to around 1000 IU (Milaneschi Y et al).
Patients should know that some research suggests that excessive vitamin D intake can lead to hypercalcemia and other conditions. This is a controversial topic, but general agreement is that the risk of toxicity is quite low and requires more research (Cranney A et al., Evid Rep Technol Assess 2007;158:1–235). The best natural sources of vitamin D are salmon, tuna, mackerel, and cod liver oil. D3 (cholecalciferol) is the supplemental form of vitamin D currently recommended.
TCPR’s Take: Given the clear general health benefits and the possible mental health benefits of adequate vitamin D, we recommend at least informing patients that there is some evidence that many people are vitamin D deficient. Whether it is costeffective to actually order a 25-hydroxyvitamin D level in depressed patients is unclear, and will require more research in order to determine the sensitivity and specificity of such testing. Vitamin D has been in the news lately, and many patients are asking whether they should take it. A reasonable response would be to recommend the moderate supplementation amounts noted previously, and to direct patients to bring the topic up with their primary care doctors, who are likely to be more current on guidelines. Treatment dosage recommendations depend on severity of deficiency, time of year, skin type, and level of sun exposure—factors which most psychiatrists would be unlikely to invest the time into learning. Nonetheless, for a good review of the current guidelines and issues, see http://bit.ly/arDPOu.
Foods for Mood
Does eating “junk food” cause or worsen depression? Conversely, is there any evidence that we should be prescribing our depressed patients specific diets?
One meta-analysis of 15 studies found that people with obesity had a 55 percent increased risk of developing depression over time, and that depressed people had a 58 percent increased risk of becoming obese (Luppino FS et al., Arch Gen Psych 2010;67(3):220–229). This finding raises the possibility of a two-way causal link between obesity and depression—with depressive symptoms leading to lifestyle changes that promote obesity, and with obesity leading to self-esteem and health issues that might cause depression.
Two recent studies have suggested that “whole” foods may be protective against depression and anxiety. One of these studies included women only, and found that a diet rich in fruits, vegetables, whole grains, meat, and fish was associated with a reduced risk of depression, anxiety, and dysthymia (Jacka FN et al., Am J Psychiatry 2010;167(3):244–247). Another large study of both men and women found an association between less healthy “processed foods” and depression over a five year period (Akbaraly TN et al., Brit J Psychiatry 2009;195(5):408–413). Both of these studies adjusted for possible confounding variables, such as socioeconomic status and age.
TCPR’s Take: While the evidence is preliminary, these studies suggest that a diet high in processed foods, fried foods, and sugar may lead to a higher risk of depression and anxiety. Therefore, we recommend that you take a basic dietary history, weigh your patients (or determine their weights from self reports), and use weight and height to calculate the Body Mass Index (BMI). (You can use a free BMI calculator at www.nhlbisupport.com/ bmi.) Encourage your patients to eat more whole foods like fruits, vegetables, and whole grains. Informational handouts and informed advice on a healthy whole food diet can help patients decide what to eat. The American Heart Association’s Nutrition Center is a great resource for patients and providers. (It can be found at www.heart. org.) The Physicians Committee for Responsible Medicine offers excellent information at www.nutritionMD.org, and free online nutrition CME for physicians and other health care providers is available at www.nutritionCME.org.
It is possible, of course, that the association is not causal, and that people who eat wholesome diets are less likely to get depressed for other reasons—for example, that they are wealthier, or have higher self esteems. However, it certainly can’t hurt to eat a healthier diet.
Light therapy is clearly effective for seasonal affective disorder (SAD), defined as depression that follows a predictable pattern of starting in the fall or winter and remitting in the spring (Rosenthal NE et al., Arch Gen Psych 1984;41(1):72–80). Is this treatment effective for non-seasonal depression as well? It’s unclear, since the largest recent meta-analysis of light therapy for this indication was inconclusive (Tuunainen A et al., Light therapy for nonseasonal depression. Cochrane Database of Systematic Reviews 2004, Issue 2).
Meanwhile, light therapy has been tested for myriad other disorders, such as treatment resistant depression, bipolar depression, ADHD, and dementia. One review of this literature found some positive results, but sample sizes were small and it was not clear how well the studies maintained the double blind (Terman, Sleep Med Rev 2007;11:497–507).
An intriguing off-shoot of light therapy is called “triple chronotherapeutic intervention” and is a combination of light therapy, partial sleep deprivation (so-called “wake therapy”), and sleep phase advance therapy (a process of resetting a patient’s sleep and wake times progressively over many days). For more information about this method, see the website for the Center for Environmental Therapeutics at www.chronotherapeutics. org. This is a nonprofit center founded by prominent researchers in the field, and the website offers free downloads of many relevant articles.
In a personal communication with us, Dr. Norman Rosenthal, considered by many to be the “father” of light therapy (see his book Winter Blues: Everything You Need to Know to Beat Seasonal Affective Disorder rev 2006; Guilford Publications, Inc: New York, NY), said that in his practice he has had success with light therapy for the common situation of patients who have nonseasonal depression, successfully treated with medication, but whose symptoms nonetheless worsen in the winter or during a period of dark weather.
Broad spectrum white fluorescent light has been used in light therapy studies for almost three decades and is considered effective and relatively safe. Dr. Rosenthal tells us that he personally recommends Verilux Happy Light, Day Light by Uplift, and SunBox, all of which are convenient for most patients and are comparatively priced. (Dr. Rosenthal has no financial relationships with any light box company.) Light boxes are not regulated by the FDA, so efficacy and safety may vary depending on the product. (See the October 2006 issue of TCPR for our test drives of some popular light boxes.)
While light-emitting diode (LED) and blue light therapy were found to be effective for SAD when compared to red light in three studies, there have been no studies comparing LED or blue light therapy with white light (Desan PH, BMC Psychiatry 2007;7(38):883–889; Glickman G et al., Biol Psychiatry 2006;59(6):502–507; Strong, RE et al., Depression Anxiety 2009; 26(3):273–278).
We recommend that most patients with SAD start light therapy toward the end of August or early September, which is when those most sensitive to light will notice shorter days. Most light boxes are 10,000 lux and patients should sit in front of them immediately after awakening for 30 minutes. The length of exposure can be titrated up or down according to response. Dr. Rosenthal cautions that bipolar depressed patients should be started at much lower durations (eg, five to ten minutes) to minimize risk of a switch into mania. Potential side effects of light therapy include headache, nausea, eyestrain, irritability, fatigue, and insomnia.
TCPR’s Take: Prescribe light therapy for patients with SAD as a matter of course, since it has established efficacy and the side effects are minimal. Consider the treatment (noting the smaller evidence base) in the following situations, as well: 1) As an adjunct for nonseasonal depression that worsens during the winter, and 2) As an adjunct for either drug- or ECT-resistant depression, regardless of seasonality of mood.
Everybody loves exercise; everybody hates exercise. We all know it’s good for us and we should do more of it, but should we be prescribing it for patients to treat their depression? Epidemiological studies show a negative association between depression and exercise (Goodwin, Prev Med 2003;36:698–703), but such studies do little to clarify the issue, since this may mean either that exercise cures depression or simply that people who are already depressed lack the motivation to exercise.
Fortunately, there are a growing number of clinical trials in which depressed patients are randomly assigned to exercise versus a wait list or treatment as usual. A recent Cochrane meta-analysis of 23 such randomized controlled trials (including a total of 907 subjects) indicated a large clinical effect for prescribed exercise treatment compared with no treatment or another controlled intervention. However, you might imagine that research on exercise has some methodological challenges, such as adequately blinding the patients and researchers to the nature of the treatment. In fact, the Cochrane authors deemed that only three of the trials had adequate blinding (of the raters only, as it is nearly impossible to blind participants to exercise), and other aspects of methodology, and limiting the analysis to these three studies yielded a much more modest effect size (Mead GE et al., Exercise for depression. Cochrane Database of Systematic Reviews 2009, Issue 3). Other meta-analyses with less strict criteria have also shown impressive benefits of exercise therapy for clinically depressed patients (Craft et al., Prim Care Companion J Clin Psychiatry 2004;6(3):104–111).
Another potential piece of evidence for exercise as a mood-booster is in the literature on fibromyalgia treatment. A Cochrane review of 2,276 subjects across 34 trials of exercise showed robust positive effects on well being and physical functioning, with less of a clear benefit for pain and tender points. The evidence was so persuasive that exercise was awarded the rare “gold level” standard of evidence (Busch AJ et al., Exercise for treating fibromyalgia syndrome. Cochrane Database of Systematic Reviews 2007, Issue 4). However, the effect of exercise for fibromyalgia may be qualitatively different than it is for depression. Part of the syndrome of fibromylagia (and chronic fatigue) is the central role that inactivity plays in perpetuating the syndrome, and exercise directly counteracts inactivity. Whether exercise works in a similarly indirect fashion in depression, or more directly as an antidepressant, is unknown.
What is the best way to talk with our patients about the benefits of exercise? Keeping in mind there is evidence that “high doses” of exercise (in frequency and intensity) alleviate symptoms better than “low doses” (Dunn et al., Am J Prev Med 2005;28(1):1–8; Martin et al., Arch Intern Med 2009;169(3):269–278), the goal is often set at about 30 minutes of moderately intense physical activity a day, three to five days a week. Of course this can be a challenging task for many of our patients who struggle with a lack of motivation and physical limitations.
Methods that have been effective in keeping people engaged include starting patients slowly to gradually build their confidence, carefully assessing each patient’s personal barriers to exercise, and having patients keep an exercise log and use a step counter. Step counters are now common and inexpensive and patients may ask your advice on how to use one. The goal of “10,000 steps a day” (five miles per day) that is publicized may be too much for many of our patients. Find out your patient’s average number of steps per day (it’s often around 3,000 steps), and slowly encourage him or her to increase steps by 1,000 to 2,000 per week. For an excellent discussion on this topic and a more detailed discussion of the practical tips listed above, see the Q&A at http://bit. ly/buykck (Otto et al., Prim Care Companion J Clin Psychiatry 2007;9(4):287–294).
For a good handout to give patients on starting exercise, including frequency and intensity, see uptodate.com’s public access patient website, www.uptodate.com/ patients, keyword: “patient information exercise.”
Meditation and Yoga
While relaxation exercises have been a part of some psychiatric practices ever since Herbert Benson wrote The Relaxation Response in 1975, lately there has been more of an interest in integrating yoga and meditation with psychiatric care. Many of these techniques have fallen within the broad term “mind/body” techniques, and there appear to be at least as many such techniques as there are mind/body practitioners. So sit down, breathe deeply, and relax—as you read our summary of the more wellresearched mind/body methods.
Meditation. For centuries many religious traditions have maintained that meditation can alleviate mental pain and increase well-being. Mental health researchers have been interested in the possibility of an inward contemplative focus to decrease anxiety and improve mood since the 1920s, in part due to the research of Edmund Jacobson and his creation of a relaxation technique known as Progressive Muscle Relaxation (PMR), a technique still often used today in many stress reduction programs.
In the 1970s stress researchers began to study meditation, dividing it into two types: “concentrative” and “non-concentrative.” Concentrative meditation directs attention to a single stimulus, such as a chant or your breathing—the most famous example being transcendental meditation (TM). In a flurry of research interest during the 1970s and 1980s TM was shown to reduce anxiety to a degree comparable to other relaxation treatments. For example, one controlled study of 31 subjects diagnosed with a “anxiety neurosis” compared biofeedback, relaxation therapy, and transcendental meditation (twice daily for 20 minutes), and found no significant differences among the three groups (Raskin et al., Arch Gen Psychiatry 1980;37(1):93– 97).
These days, we are likely to hear more about “mindfulness training” than about TM. Mindfulness differs from TM and some other meditative techniques in that the aim is to maintain a moment-to-moment awareness of all of the contents of your mind, as opposed to just restricting focus to a single mental task, such as repeating a mantra or staring at a candle.
Mindfulness training was popularized and researched extensively by Jon Kabat Zinn at the University of Massachusetts Medical School in a form called mindfulness-based stress reduction (MBSR). MBSR originated as a group-based program to help with chronic pain and stress associated with other medical conditions, and was later studied to treat anxiety disorders (Kabat Zinn, Am J Psychiatry 1992;49(7): 936–943).
An offshoot of MBSR is Mindfulness Based Cognitive Therapy (MBCT), which combines the principles of mindfulness group meditation with elements of cognitive therapy. Unlike traditional CBT, however, there is little emphasis on challenging the contents of thoughts—instead the patient is taught to become nonjudgmentally aware of his/her thoughts and feelings. The problem, according to MBCT, is that depressed patients try to think their way out of their dysphoric mood, which leads to rumination (“What’s wrong with me?” “Why do I always feel overwhelmed?”), and therefore worsens depression. This “doing” mode of mind is second nature to most of us, but it can paradoxically worsen depression. In contrast, mindfulness meditation cultivates a “being” mode, involving watching your feelings drift by like clouds in the sky. By doing so, the meditator begins to notice and to halt the internal triggers that can spiral into hopelessness.
There are several randomized clinical trials demonstrating the effectiveness of MBCT to prevent depressive relapses compared to treatment as usual (TAU) (Teasdale et al., J Consult Clin Psychol 2000;68(4):615–623; Bondolfi et al., J Affect Disord 2010;122(3):224–231). The Bondolfi study, for example, enrolled 60 unmedicated patients who were in remission from a recurrent depression, and randomly assigned them to either TAU or TAU plus MBCT. Although both groups eventually relapsed at similar rates, the time to relapse was much longer in the combined group (204 days compared to 69 days for the TAU group). For a good book describing the MBCT method for preventing depressive relapse written for clinicians and patients alike see “The Mindful Way through Depression” written by Mark Williams et al., Guilford Press, 2007 (it includes a nice CD to assist with meditation practices as well).
Just to confuse matters even more, there are a growing number of “mainstream” cognitive therapies that now include mindfulness practices, such as Acceptance and Commitment Therapy (ACT). In contrast to MBCT, which is a group treatment built around daily meditation practices, ACT is an individual psychotherapy that uses a variety of cognitive techniques including mindfulness. The idea here is that trying to control uncomfortable feelings and thoughts is not just ineffective but counterproductive. Instead, ACT encourages patients to accept their full range of emotional and cognitive experiences while also identifying key personal values that can be translated into behavioral goals. In a recent metaanalysis of 18 randomized control trials (n=917), ACT was superior to waiting lists and treatment as usual, though not significantly more effective than established treatments, such as CT, CBT, and problem solving (Powers et al., Psychother Psychosom 2009;78(2): 73–80). For a good introduction on ACT for clinicians and patients, see “The Mindfulness and Acceptance Workbook for Anxiety” by Forsyth and Eifert, Harbinger Press, 2007 (it also includes a CD with meditation instructions).
TCPR’s Take: Meditation has become mainstream, and the future is in integrating components of its benefits into psychotherapy.
Yoga. Although the term yoga evokes the image of drawstring-clad practitioners who have formed themselves into improbable postures, the word itself—roughly translated from Sanskrit—means “to unite,” and is a general term in Hinduism for the various means by which a person can connect with Brahman, the universal consciousness. The type of yoga most commonly practiced in the U.S. is called Hatha yoga, which focuses on postures (called asanas). Hatha yoga combines meditation, yoga postures and philosophy to promote well-being. There are a confusing number of different yoga practices, ranging from Ashtanga yoga (sometimes called “Power yoga”), a fast-paced intense style of yoga that is physically demanding, to Iyengar yoga, which focuses on precise body alignment and holding poses over long periods.
Does research support yoga as a treatment for psychiatric disorders? A 2005 literature review identified five randomized controlled trials, each of which used different types of yoga interventions to treat depression. All of the trials reported positive results but all had methodological shortcomings (Pilkington et al., Journal of Affect Disord 2005;89:13–24).
One of the few (and best) randomized trials demonstrating the usefulness of yoga examined a technique called Sudarshan Kriya yoga (SKY). In this study, 45 depressed hospitalized patients were randomized to SKY, imipramine (150 mg–225 mg/day) or ECT for four weeks. Reductions in depression measured by the Beck and Hamilton depression rating scales occurred in all three groups, with imipramine and SKY performing similarly, both inferior to ECT (Janakiramaiah N et al., J Affect Disord 2000;57(1–3):255–259). A recent randomized trial of 46 individuals with major depression or dysthymia compared three treatments: yoga with meditation (not SKY), group therapy with hypnosis, and psychoeducation (considered the control group). Significantly more participants in the yoga group experienced a remission than did controls at a nine month follow up. Remission rates in the hypnosis group did not significantly differ from the control group (Butler et al., Journal of Clinical Psychology 2008;64(7):806–820).
Yoga is often used to treat anxiety, and a 2005 review located eight studies, all with positive results, but again the authors noted the “poor quality” of most of the studies (Kirkwood et al., Br J Sports Med 2005;39(12):88–91). One of the better trials in this review randomized 91 subjects with a DSM-III diagnosis of “anxiety neurosis” to either five days per week of yoga practice or diazepam (no dose or frequency given) for three months. Those assigned to yoga had significantly lower anxiety scores at the end of the trial than patients taking diazepam (Sahasi et al., J Pers Clin Stud 1989;5:51–55).
Recent trials have found women in particular may benefit from yoga’s antianxiety effects. One study showed a significant decrease in anxiety for only the women who were randomized to a twice weekly yoga class for 90 minutes compared with a control group (Javnbakht et al., Complement Ther Clin Pract 2009;15(2):102–104). Similarly, another recent trial randomly assigned 98 women with breast cancer to either 60 minutes of yoga once a day or brief supportive therapy and found an overall decrease in several anxiety measures in the yoga group compared to the brief supportive therapy group (Rao et al., Complement Ther Med 2009;17(1):1–8).
TCPR’s Take: Yoga can be a useful adjunctive treatment for both depressed and anxious patients, and may be particularly helpful for women—but the research is still quite limited.