Just as the IM intake described above is comprehensive and holistic, so too may be the treatment. The integrative treatment of major depression is an instructive example in which to explore the clinical application of IM to behavioral health, since it incorporates a broad spectrum of modalities that demonstrate well this holistic approach. The approach includes conventional therapies when indicated (e.g., pharmaceuticals, psychotherapy), though these are beyond the scope of this chapter (see Chapter 25). The key integrative therapies that are most frequently used are foundational health practices (nutrition, exercise, sleep, and stress management), light, mind–body therapies (e.g., meditation, guided imagery), and botanical medicines and supplements (e.g., St. John’s wort). Some studies suggest that transcranial magnetic stimulation may be beneficial. Energy medicine therapies (e.g., Reiki), manual medicine techniques (e.g., osteopathy, massage), aromatherapy, and alternative systems (e.g., Traditional Chinese Medicine, homeopathy) may also be used, although there is less research evidence for these at present.
Foundational Health Practices: Nutrition, Exercise, Sleep, Stress Management
Nutrition: Food affects mood through a variety of mechanisms such as nutritional deficiencies, psychoactive foods (e.g., alcohol, caffeine), hunger (possibly including hypoglycemia), and food intolerances (e.g., celiac disease, fructose intolerance). Integrative treatment of depression, therefore, includes a comprehensive assessment of the patient’s diet. General guidelines for nutrition in depression are:
Eating mostly whole foods (e.g., grains, legumes) and few or no refined foods (e.g., processed cereal, sweetened beverages, and baked goods)
Eating copious amounts of vegetables and fruits
Reducing or eliminating alcohol, caffeine, and sugar
Choosing healthy fats (e.g., fish and plant-derived) more often than unhealthy fats (polyunsaturated vegetable oils, animal-source saturated fats, trans fats)
Using healthy snacks to avoid hunger between meals
Though results are mixed, some research has found a beneficial effect of supplementing with key nutrients, such as folate or omega-3 fatty acids from fish oil, either as monotherapy or as adjunctive therapy to pharmaceutical medicines for depression.
Exercise: Exercise has been shown to be beneficial for mild-to-moderate depression in some clinical trials. Many forms of aerobic exercise (e.g., running, walking, dancing), strength training, and mindful exercise (e.g., tai chi, qi gong) may be beneficial. Certainly, exercise should be a part of any wellness program for those who are able to participate.
Sleep: Sleep is another foundational health practice that affects mood (see Chapter 31). Chronic insomnia, for example, is a risk factor for depression. Integrative assessment of a patient with depression includes evaluation of sleep health. Recommendations for sleep health in a depressed patient, known as “sleep hygiene,” are:
Light transition is helpful (gradually reducing amount of ambient light until ready for sleep). If this is too much trouble, then it is recommended to at least avoid bright light for the hour preceding bedtime. The sleep room should be thoroughly darkened. Illuminated clocks or any light-emitting devices should be off or facing away from the eyes.
It is recommended that the following be avoided in the period of time before sleep: vigorous physical exertion, mental stimulation, problem-solving or other task-oriented cognitive function, and loud or emotionally provocative stimuli. Meditation or prayer can be ideal. Relaxation exercises are useful. Listening to calming music or other calming sound can also be useful. Many people find aromatherapy helpful for falling asleep (e.g., lavender, chamomile).
The bed is for sleep or intimacy only. One should not read in bed, eat in bed, nor watch television in bed. This helps to condition the mind so that when one goes to bed the mind becomes calm rather than remaining active.
Stress Management: The last of the four foundational health practices, stress management, is very important in the integrative treatment of depression. Stress has a strong causal relationship with major depression, and mind–body therapies that reduce stress have proved to be beneficial (see Chapter 34).
Light, or phototherapy, is an effective treatment for seasonal affective disorder (SAD), and may also be helpful as an adjunctive treatment of nonseasonal depression as well. Bright, full-spectrum light (10,000 lux) of 30–60 minutes in the morning from an appropriate bulb has been studied, but natural sunlight is likely to be effective also. This exposure to appropriate artificial or natural light is part of a comprehensive IM treatment plan for depression.
Mind–body medicine is commonly defined as the field of medicine that uses processes of the mind to influence the health of the body. This is a useful definition with which to start, but it is important to note that it can perpetuate the mind versus body dualism, and it fails to acknowledge the bidirectional relationship of mind and body, that is, not only does the state of mind affect physical health (e.g., depression worsens coronary artery disease outcomes) but the state of the physical body can affect mental state (e.g., aerobic exercise improves mood). It may be more accurate to think of mind/body as a single entity, where the health of one part necessarily influences the health of the other. Examples of mind–body therapies are meditation, guided imagery, biofeedback, hypnosis, progressive muscle relaxation, breathing exercises, yoga, tai chi, and qi gong.
Mind–body therapies can be useful for treating depression. A Cochrane review and meta-analysis of 11 trials of relaxation therapies (e.g., progressive muscle relaxation, relaxation imagery, autogenic training) found significant reduction in self-rated depressive symptoms compared with no treatment. Mindfulness-based programs (mindfulness-based stress reduction [MBSR] and mindfulness-based cognitive therapy [MBCT]) have shown benefit in treating depression and preventing relapse.
Botanical Medicines and Supplements
The botanical medicine St. John’s wort and the supplement S-adenosylmethionine (“SAMe”) are the two nonpharmaceutical medicines that have the most research evidence supporting their use in the integrative treatment of depression.
St. John’s Wort (Hypericum perforatum)
St. John’s wort is a perennial plant, with a yellow flower, native to Europe and naturalized to North America. It is one of the oldest medicinal botanicals of Europe. Over the past two decades, St. John’s wort has been studied in thousands of patients for the treatment of depression. Several well-designed randomized, controlled clinical trials (RCTs) have found that St. John’s wort is more effective than placebo for the treatment of mild-to-moderate depression and has fewer side effects than pharmaceutical antidepressants. Other recent RCTs have not replicated these findings, leading some experts to not endorse the use of St. Johns wort for this purpose. As with all treatment modalities, clinicians should discuss the potential risks and benefits of the treatment with their patients and come to a decision through a shared decision-making paradigm.
St. John’s wort inhibits serotonin, norepinephrine, and dopamine reuptake in the central nervous system and may modulate autonomic system reactivity. As an oral medicine it is very well tolerated. Data from 35 double-blind randomized trials show that drop out and adverse event rates in patients receiving Hypericum extracts were less than that for tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRI). Side effects include gastrointestinal upset, photodermatitis, mild headache, and restlessness. Cases of withdrawal symptoms similar to those that occur with SSRI antidepressants have been described, so gradual tapering of dose is recommended when therapy is terminated. Patients are advised to avoid taking St. John’s wort in combination with prescription antidepressants because there have been case reports of serotonin syndrome. Importantly, St. John’s wort also potently induces the cytochrome P450 system (isozyme CYP3A4), which may lower the blood levels of medications that are metabolized by this system (e.g., alprazolam, ethinyl estradiol, warfarin, cyclosporine, statins, and indinavir). St John’s wort can also lower the serum level of medications by increasing activity of the P-glycoprotein transporter system, thereby increasing drug excretion through the gastrointestinal mucosa. St. John’s wort has the potential for multiple herb–drug interactions through induction of the CYP3A4 and P-glycoprotein systems. Concurrent use of St. John’s wort and medications metabolized by these systems should be avoided.
The usual dose of St. John’s wort is 300 mg three times daily of a preparation standardized to hypericin (0.3%) or hyperforin (2–5%).
S-adenosylmethionine (SAMe) is a naturally occurring compound made in the human body that facilitates transmethylation reactions, such as those that occur in neurotransmitter metabolism. Levels of SAMe are dependent on B-vitamin concentrations. Although the exact mechanism of its antidepressant effect is not known, SAMe is associated with increased serotonin turnover and increased dopamine and norepinephrine levels in the brain.
There have been more than a dozen randomized controlled trials on SAMe for depression; although most of these studies show benefit, several examined parenterally administered SAMe, and there were methodological limitations to many.
S-adenosylmethionine appears to be safe. Side effects include gastrointestinal upset (nausea, vomiting, diarrhea) and psychomotor stimulation (insomnia, anxiety, restlessness). There have been cases of mania and hypomania in people with bipolar disorder who have taken SAMe, hence, it should be avoided in this population. SAMe can lower blood glucose levels and, therefore, should be used cautiously in patients taking hypoglycemic agents. SAMe might interfere with the action of levodopa in those with Parkinson disease.
The dose of SAMe for depression is 800–1600 mg daily. The cost of this supplement is high, relative to other over-the-counter supplements.
A 26 year-old male graduate student in the chemistry department of a university presents to an IM physician complaining of “feeling unhappy a lot”, “stressed out”, “just working all the time,” and “out of touch with life.” He confirms that his work and social life have suffered due to persistent low mood. He has no prior history of major depression, but does describe previous periods of “doldrums” in his adult life. He began weekly psychotherapy for the first time 1 year ago. He began taking an SSRI antidepressant for the first time 8 months ago, has never been hospitalized for mental illness, and has no history of suicidality. He does not drink alcohol nor use illegal substances. He prefers to work in the laboratory late in the evening, goes to bed between midnight and 1 A.M., has trouble falling asleep due to anxiety, awakens between 8 and 9 A.M., and does not feel alert until early afternoon. He either skips breakfast or eats a bagel with jam. In the mid-afternoon, he eats a burrito or sandwich, and he purchases take-out food from one of the local restaurants for dinner. He is anxious about a wide variety of things in his life (career, family, social life, health) and finds that his mind is mostly occupied with anxious thoughts when he is not focused on work. He was raised in the Catholic tradition and misses the participation that he recalls when he was younger. He exercises on the weekends occasionally, going to a local gym to run on the treadmill. He misses the team soccer he enjoyed regularly in his twenties. His weekly psychotherapy has been helpful, as has the SSRI, but he still feels lonely, anxious, and “not fully alive.”
Because this patient may have major depression and possibly a generalized anxiety disorder, the IM approach to his case would include a discussion of pharmaceutical augmentation options. Nonpharmaceutical suggestions would address his foundational health practices, light, social and spiritual health, the use of mind–body medicine modalities, and supplements.
Regarding his nutrition, it would be recommended to never skip breakfast and to include all three macronutrients (protein, carbohydrate, fat) in that meal. To ensure adequate amount of B vitamins the patient could be asked to include more B vitamin rich foods in his diet or temporarily begin a B vitamin complex supplement. Increasing the quantity of whole foods, fruits, and vegetables would also be recommended for general nutritional benefit.
Regarding exercise, it would be strongly advisable to do more regular aerobic exercise. Due to his circadian rhythm phase shift, ideally this exercise would occur in the morning. His previous enjoyment of soccer and the social interaction that it offers as a team sport offer additional potentially therapeutic options. For example, he could do 30 minutes of vigorous aerobic exercise most weekday mornings and participate in soccer matches on weekends.
Regarding sleep, it would be important to address his behaviors around sleep (i.e., sleep hygiene) as well as the anxiety that interferes with falling asleep. Additionally, preliminary research suggests that shifting his circadian rhythm earlier would be helpful in improving mood.
At least 30 minutes of natural or appropriate artificial light in the morning would be another helpful adjunct in the treatment of this patient’s mood. If an outdoor morning exercise routine could be established, then this may be accomplished naturally; however, a light box would be an effective alternative.
Exploring his nostalgia for the Church would be another important element in his integrative treatment plan. In addition to the benefit from spiritual practice, this could offer another social support and even a spiritually congruent way to introduce a mind–body practice. Centering Prayer, a method with ancient roots but developed in the 1970s, is a practice that shares much of the form and benefits of meditation.
Other mind–body practices that may be helpful for this patient are MBSR and the 4-7-8 breath. Mindfulness-based stress reduction is an 8-week program that is proven to help depression, anxiety, and sleep. It may also be particularly helpful with his complaint of “being out of touch with life,” since mindfulness is an attentional training method that emphasizes present moment awareness (see Chapter 7). The 4-7-8 breath is derived from ancient breath practices known as pranayama, a branch of Ayurveda. The 4-7-8 method is easy, fast (2–3 minutes), and useful for acutely reducing anxiety and sympathetic tone.
Because the patient is on an SSRI, addition of St. John’s wort would not be indicated. One could cautiously augment with SAMe; however, the anxiety component of this case argues against its use because SAMe can be stimulating and actually cause or exacerbate anxiety. Supplementation with fish oil may be useful for augmentation in this case and is very unlikely to be harmful.
Many other aspects of his case would of course also be explored, such as checking thyroid function if that has not already been done, checking testosterone and DHEA (dehydroepiandrosterone) levels if other symptoms of hypoandrogenism are present, addressing any other particular psychological tendencies of this patient (e.g., poor self-esteem), and discovering what most gives him a sense of meaning and purpose.