WHOLE HEALTH: CHANGE THE...

WHOLE HEALTH: CHANGE THE CONVERSATION Advancing Skills in the Delivery of

Personalized, Proactive, Patient-Driven Care

This document has been written for clinicians. The content was developed by the Integrative Medicine Program, Department of Family Medicine, University of Wisconsin-Madison School of Medicine and Public Health in cooperation with Pacific Institute for Research and Evaluation, under contract to the Office of Patient Centered Care and Cultural Transformation, Veterans Health Administration.

Information is organized according to the diagram above, the Components of Proactive Health and Well-Being. While conventional treatments may be covered to some degree, the focus is on other areas of Whole Health that are less likely to be covered elsewhere and may be less familiar to most readers. There is no intention to dismiss what conventional care has to offer. Rather, you are encouraged to learn more about other approaches and how they may be used to complement conventional care. The ultimate decision to use a given approach should be based on many factors, including patient preferences, clinician comfort level, efficacy data, safety, and accessibility. No one approach is right for everyone; personalizing care is of fundamental importance.

Depression Educational Overview

WHOLE HEALTH: CHANGE THE CONVERSATIONDepression

Educational Overview

Vignette: Frank

The following is based on a patient vignette developed by the VA Office of Patient-Centered Care and Cultural Transformation.

Frank is a 64-year-old retired Vietnam Veteran who receives his care at a large urban Community-Based Outpatient Center (CBOC). His primary care physician (PCP), whom he has been seeing for a couple of years now, is concerned that Frank has been depressed. He scored a “9” on the Patient Health Questionnaire (PHQ-9), indicating mild depression, but he has scored higher in the past. Six months ago, he was given a suicide risk evaluation, and he was assessed as being a low overall risk. He declined medications at that time because he did not tolerate three medications prescribed in the past. His PCP is wondering what other options to consider to help him.

Frank has been coming to the VA for care for a number of years. His wife died 10 years ago, and Frank has been living alone since then. He struggled with depression when his wife died, but with the support of family and a Veterans’ grief group, he got back on his feet and has been coping well. Recently, he has lost several of his friends and is beginning to feel the effects of aging.

He believes his physician is right about his needing to do more about his depression, but he just does not want to take a bunch of pills. No other options or strategies have been offered to him at this point, and this makes him feel more hopeless.

Frank’s PCP recently suggested that Frank take home and fill out a Personal Health Inventory (PHI) to help identify what really mattered to him. His PCP asked him to schedule a telephone visit with him in one week and to come to the clinic in two weeks to meet with a nurse on his patient-aligned care team (PACT) to talk about the inventory. Frank agreed.

As he worked through the inventory, it became very clear to Frank that the thing that gave him most joy was his grandchildren. Whenever he was with them, or thought about them, he had more energy and felt happy.

VHA Office of Patient Centered Care and Cultural Transformation Page 1 of 42

WHOLE HEALTH: CHANGE THE CONVERSATION Educational Overview: Depression

Your Personal Health Inventory

1. What really matters to you in your life?My family is important to me.

2. What brings you a sense of joy and happiness?Being a good role model for my family. I feel great whenever I talk to my

grandchildren or I’m spending time with them.

3. On the following scales from 1-5, with 1 being miserable and 5 being great, circle whereyou feel you are on the scale.

Physical Well-Being:

1 2 3 4 5

Miserable Great

Mental/Emotional Well-Being:

1 2 3 4 5

Miserable Great

Life: How is it to live your day-to-day life?

1 2 3 4 5

Miserable Great

Where You Are and Where You’d Like to Be For each of the following areas, consider where you are now and where you would like to be. All the areas are important. In the “Where you are” box, briefly write the reasons you chose your number. In the “Where you want to be” box, write down some changes that might make this area better for you. Some areas are strongly connected to other areas, so you may notice some of your answers seem the same. Try to fill out as many areas as you can. You do not have to write in every area or in all the areas at one time. You might want to start with the easier ones and come back to the harder ones. It is OK just to circle the numbers.

Pers

onal

Hea

lth In

vent

ory

(PHI

)



Working the Body: “Energy and Flexibility” includes movement and physical activities like walking, dancing, gardening, sports, lifting weights, yoga, cycling, swimming, and working out in a gym. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5

Where would you like to be? 1 2 3 4 5

What are the reasons you choose this number?

I don’t get out and do things as often as I

should. I spend a lot of time sitting in the

house and listening to talk radio.

What changes could you make to help you get there?

Whenever I go out for a walk, I feel better,

so I want to do this more.

Recharge: “Sleep and Refresh” includes getting enough rest, relaxation, and sleep. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



I feel drained, but I can’t sleep after lying

around all day. I feel the saddest at night,

and I keep thinking about the people I’ve

lost.


Walking every day might help, and maybe I

could talk to one of my grandchildren in

the evening.

Food and Drink: “Nourish and Fuel” includes eating healthy, balanced meals with plenty of fruits and vegetables each day, drinking enough water and limiting sodas, sweetened drinks, and alcohol. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



I know I don’t eat as healthy as I could. I’ve

been eating a lot of frozen dinners and

packaged food lately. I sometimes have a

couple of cocktails in the evening before I go

to bed.


I could probably avoid fast food more.

Personal Development: “Personal Life and Work Life” includes learning and growing, developing abilities and talents, and balancing responsibilities where you live, volunteer, and work. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



Since I’ve retired, I’ve been spending a lot of

time around the house. So many of my

friends have died.


It would probably be good for me to get

out and do something, but I just don’t

know what it would be.

Pers

onal

Hea

lth In

vent

ory

(PHI

)



Family, Friends, and Co-Workers: “Relationships” includes feeling listened to and connected to people you love and care about, and the quality of your communication with family, friends, and people you work with. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



I have a very supportive family. I miss my

grandchildren. I always feel better when I

see them. I wish I could see them more, but

they don’t live in the same city, and it’s

hard for me to visit them as often as I’d

like. Although several of my friends have

died, I still have a few good friends left.


I guess I could try to see my friends more

often, but I can’t afford to travel to see my

grandchildren.

Spirit and Soul: “Growing and Connecting” includes having a sense of purpose and meaning in your life, feeling connected to something larger than yourself, and finding strength in difficult times. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



When my wife died, that changed who I

thought I was. Now that I’ve retired and my

children are all grown up, I just don’t know

what my role in life is anymore. When I was

working and married I had a purpose. I was

a husband and father and had a family to

take care of.


I just don’t feel connected to what matters

to me, so I guess I need to figure that out.

I need to figure out what my purpose is

again.

Surroundings: “Physical and Emotional” includes feeling safe, having comfortable, healthy spaces where you work and live, quality of the lighting, color, air, and water, and decreasing unpleasant clutter, noises, and smells. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



I’m pretty comfortable where I live. I know

my neighbors. I feel safe going out for a

walk. The grocery store and places I need to

go are in walking distance.


I’m satisfied with my house the way it is.

Pers

onal

Hea

lth In

vent

ory

(PHI

)



Power of the Mind: “Strengthen and Listen” includes tapping into the power of your mind to heal and cope and using mind-body techniques like relaxation, breathing, or guided imagery. Where you are: Rate yourself on a scale of 1 (low) to 5 (high) 1 2 3 4 5



I don’t really know what this means. I am

not the kind of person who is going to

meditate or anything like that.


I think I am fine where I am. Maybe I could

learn a little more about what this means.

Professional Care

Prevention: On a scale of 1-5, circle the number that best describes how up to date you are on your preventive care such as flu shot, cholesterol check, cancer screening, and dental care.

1 2 3 4 5 Not at all A little bit Somewhat Quite a bit Very Much

Clinical Care: If you are working with a healthcare professional, on a scale of 1-5, circle the number that best describes how well you understand your health problems, the treatment plan, and your role in your health.

1 2 3 4 5 Not at all A little bit Somewhat Quite a bit Very Much

I am not working with a healthcare professional.

Reflections

1. Now that you have thought about all of these areas, what is your vision of your bestpossible health? What would your life look like? What kind of activities would you bedoing?In some ways, I’m in pretty good shape. It’s nice to see that not everything about

me is broken. I can see that so many things tie back to my relationship with my

grandchildren. I feel motivated to work on things that might help me be a better

grandfather who can be there for them.

2. Are there any areas you would like to work on? Where might you start?If I can figure out ways to feel happier, I know I will be the role model I want to be

for my grandchildren. The best case would be for me to be an active part of their

lives.

Pers

onal

Hea

lth In

vent

ory

(PHI

)



First Things First: Be Aware of Suicide Risk

Frank is not currently at high risk of suicide, but it must always be kept in mind when one is seeing a patient with depression, or other conditions that predispose to higher suicide risk, like posttraumatic stress disorder (PTSD), sleep disorders, substance use problems, and chronic pain. Some key resources to assist with assessing for suicide risk:

• VA Crisis line. Call 1-800-273-8255 and Press 1. http://veteranscrisisline.net/• Suicide Risk Management Training for Clinicians (online

manual) http://www.mentalhealth.va.gov/communityproviders/docs/VA_Suicide_RMT.pdf

• Community Provider Toolkit: Suicide Prevention Basicshttp://www.mentalhealth.va.gov/communityproviders/clinic_suicideprevention.asp - sthash.EV6SsvnS.dpbs.

Introduction

Using the vignette of Frank as an example, this educational overview will review how a clinician might approach a Veteran with depression using a Whole Health approach. Information is organized based on the Components of Proactive Health and Well-Being (Circle of Health), which you will find on the front page of this document. An overall evidence rating summary for various therapies is offered at the end.

Frank is not alone. One in ten adult Americans suffers from a depressive disorder. Depression is the most common mental illness.1 Fourteen percent of U.S Veterans have been diagnosed with depression, but studies indicate it is under diagnosed in this population.2

Not surprisingly, depression is one of the chronic conditions for which alternative therapies are most frequently used.3 The 2011 Complementary Alternative Medicine Survey (HAIG Report), which surveyed 141 VA facilities, found that depression was the fourth most common diagnosis for which Veterans were treated within the VA using complementary therapies.4 Most popular among these were

• Stress management and relaxation therapy (66 facilities)• Mindfulness (62 facilities)• Guided imagery (61)• Progressive muscle relaxation (44)• Biofeedback (41)

For more information on each of these approaches, see the Power of the Mind module.


http://veteranscrisisline.net/

http://www.mentalhealth.va.gov/communityproviders/docs/VA_Suicide_RMT.pdf

http://www.mentalhealth.va.gov/communityproviders/docs/VA_Suicide_RMT.pdf

http://www.mentalhealth.va.gov/communityproviders/clinic_suicideprevention.asp%23sthash.EV6SsvnS.dpbs

http://www.mentalhealth.va.gov/communityproviders/clinic_suicideprevention.asp%23sthash.EV6SsvnS.dpbs


Personalizing Care

It makes sense to meet patients where they are at with their symptoms and the severity of their presentation and target treatment accordingly. A Whole Health approach that combines conventional care with self-care, complementary therapies, the use of a team, community support, and other interventions, can have potential benefit. The goal is to personalize care to the needs of each individual Veteran, partnering with each one to create a Personal Health Plan (PHP) that they truly identify as their own and are willing to follow.

One important aspect of individualizing care is recognizing that depression can manifest in many different ways. Examples in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) include5

• Disruptive mood dysregulation disorder• Major depressive disorder (including minor depressive episodes)• Persistent depressive disorder (dysthymia)• Premenstrual dysphoric disorder• Substance/medication-induced depressive disorder• Depressive disorder due to another medical condition• Other specified depressive disorder• Unspecified depressive disorder (This is the most common category).

Even how one of these diagnoses presents can vary from one person to another in terms of symptom duration, time course, and presumed etiology.6 Again, each person is different, and care must be individualized. For instance, some people manifest depression by withdrawing; others express it more through anger. Some experience strong feelings, while others say they cannot feel anything.

A large majority of depressed patients present primarily with somatic complaints rather than complaining of depressed mood.7 Screening for depression is important and should be done routinely. The Patient Health Questionnaire (PHQ-9) is a simple, well-validated instrument for diagnosing depression and measuring treatment outcomes in the primary care setting and can be accessed at http://www.cqaimh.org/pdf/tool_phq9.pdf.8 This site also offers background information on the questionnaire and describes how to score it.

Many studies find that a strong therapeutic relationship between a clinician and a patient is an important contributor to positive outcomes. In some studies, an empathic clinician with a placebo has had better results than a less empathic clinician with medications.9

VHA currently mandates routine screening for depression in ambulatory settings and supports access to depression treatment through comprehensive mental health services, including primary care-mental health integration programs. Timely suicide risk assessment following positive depression screens is currently a VHA performance measure. For more


http://www.cqaimh.org/pdf/tool_phq9.pdf


specific evidence related to resources available to Veterans through the VA, go to one of the following websites:

• VA Community Provider Toolkit: Serving Veterans ThroughPartnership http://www.mentalhealth.va.gov/communityproviders/index.asp#sthash.CoUqQUWt.VdcjGHTG.dpbs

• VA Mental Health Resources for Veterans withDepression http://www.mentalhealth.va.gov/depression.asp

Mindful Awareness and Depression

Mindful awareness has been described as a practice of learning to focus attention on moment-by-moment experience with an attitude of curiosity, openness, and acceptance. (For details, see the module, Mindful Awareness.) Mindful awareness is a general approach to living, but it can be used to work with many specific issues or concerns, and depression is no exception. A particularly helpful resources is the book The Mindful Way Through Depression, by Mark Williams and colleagues.10 Specific techniques that invoke mindful awareness are featured in the Power of Mind section, below.

Proactive Self-Care and Depression

Working Your Body • Exercise

Exercise has been extensively advocated to benefit and promote health for centuries, with thousands of studies on depression, mostly showing that exercise helps.11 Exercise alone offers effective treatment for mild to moderate depression when compared to medication or psychotherapy. Combining exercise with those approaches appears to be even more effective.12,13 In addition to decreasing symptoms, further benefits include reduced risk for relapse, improved self-esteem, and, of course, higher levels of physical fitness.14,15

Exercise has been shown to regulate neurotransmitters and promote nerve cell growth; exactly how it affects depression is unknown.16,17 Lucassen suggests it may be due to changes in nerve cell development in the brain.18 Reduction in nerve cell growth and toxicity in the hippocampus are thought to be mediated through pro-inflammatory chemicals, such as IL-6. Increases in macrophage activity and in the production of pro-inflammatory cytokines have been consistently reported in depressed patients.19 It has been shown that exercise can alter cellular immunity and reduce markers of inflammation, thereby modifying the metabolism of the key neurotransmitters involved in depression.18

The most recent Cochrane Review that focused on exercise for depression included 39 studies with a total of 2,326 participants; it concluded that exercise is20

o “…[M]oderately more effective than no therapy.” This effect becomes lessclear when only high-quality studies are evaluated.


http://www.mentalhealth.va.gov/communityproviders/index.asp%23sthash.CoUqQUWt.VdcjGHTG.dpbs

http://www.mentalhealth.va.gov/communityproviders/index.asp%23sthash.CoUqQUWt.VdcjGHTG.dpbs

http://www.mentalhealth.va.gov/depression.asp


o No more effective (but also not less effective) than antidepressants orpsychological therapies. This is based on a small number of studies.

Aerobic and non-aerobic activities are equally effective.21 Total energy expenditure becomes more important than the number of times per week someone exercises. How much exercise per week is needed is not clear, but aiming for 150 minutes of total weekly exercise is reasonable.

Exercising on an ongoing basis does make a difference. Consistency is key, and it is essential for patients to establish a routine they will adhere to. It is important to help the Veteran brainstorm about barriers that might get in the way of doing regular activity and generate ideas about how to overcome them. An example would include walking indoors at a local mall if the weather outside is bad.

We know that exercise may produce immediate improvement in mood.22 Therefore, starting systematic exercise early on in a depressive episode may be especially beneficial during the period when medication and psychotherapy have a delayed onset of effect.

While reviews are not entirely clear on the benefits of exercise relative to medications and psychological therapies, it would seem that they have comparable effects. Because exercise has rapid effects for many people, it can serve as an important part of a PHP for a depressed person.

See the Working Your Body module for more information.

• YogaYoga should perhaps best be viewed as a way to promote good overall physical andmental health, rather than as a specific intervention for depression. Potentialreasons for yoga to have positive effects on depression include modulation of theHPA axis, regulation of neurotransmitters, decreases in rumination, promotion ofmore adaptive thinking, and behavioral activation.23

Compiling study data related to yoga as a treatment for depression is challenging.There are many different forms of yoga, and practices stem from many diversetraditions incorporating a wide variety of techniques. A recent meta-analysis foundthat 12 randomized controlled trials (with some methodological limitations noted)of 619 participants concluded yoga had moderate short-term beneficial effects onseverity of depression, compared to usual care. 24 It was less beneficial than aerobicexercise or relaxation. Based on their findings, the authors suggest that yoga beconsidered an ancillary treatment option for patients with depression.

Practicing yoga requires having a trainer, especially if a patient has physicaldisabilities. Beginners should avoid extreme practices such as headstands, lotusposition, and forceful breathing. Individuals with medical preconditions should



work with their physicians and yoga teachers to appropriately adapt postures. Those with glaucoma should avoid inverted positions, and patients with high fracture risk should avoid forceful yoga practices.25 For more information see the Yoga: Looking Beyond “The Mat” clinical tool.

• Tai chiA recent meta-analysis found evidence to suggest both short and long-term tai chipractices (40-minute sessions, ranging from one to four sessions per week over acourse of 6 to 48 weeks) reduce depression symptoms.26 This data was pooledbased on a total of 2,008 patients, from randomized control trials, non-randomizedcomparison studies, and observational studies. No adverse events related to the useof tai chi for depression treatment have been reported.

Surroundings • Light therapy

Sleep and circadian rhythm disturbances are significant symptoms of depression. A large meta-analysis of psychopathological symptoms of circadian rhythm disorders was able to distinguish depressed patients from normal controls.27 Serotonin receptor binding potential (which is associated with depression) is negatively correlated with the duration of daily sunshine one receives. Serotonin receptor binding lowers with increased sunlight during spring and rises when sunlight decreases in the fall.28 High serotonin receptor density is associated with low extracellular serotonin and vice versa.29 Therefore, it comes as no surprise that light therapy has been commonly used for patients with seasonal affective disorder and has been found useful as an adjunctive modality with pharmacotherapy in both unipolar and bipolar depression.30 As a primary treatment, light therapy may be recommended as a one to two week time-limited trial in mild to moderate seasonal depression.31 In more severe forms of seasonal depression, light therapy is recommended as adjunctive to medications.

A few meta-analyses, including Cochrane review, supported at least modest benefit of bright light therapy when compared with placebo for non-seasonal depression.31,32 Furthermore, APA guidelines for the treatment of major depressive disorder, both seasonal and non-seasonal, consider bright light therapy a low-risk and low-cost option.33 The exact mechanism of action is still unknown; however, based on the above evidence, it is thought to be mediated through the serotoninergic neurotransmitter system and is therefore considered a biologic treatment. There are a few side effects to bear in mind when recommending light therapy. Headache, eye strain, nausea, agitation and potential hypomania induction in some patients with bipolar disorder may occur.34

Light therapy dosing recommendations range from 30 to 60 minutes of full-spectrum (10,000 Lux) light daily from special bulbs, or non-direct daylight exposure in the early morning. One should not stare directly at a light source. Therapy is effective so long as light is able to meet the eye at an angle of 30–60°. 35



If depressive symptoms seem to have a seasonal pattern, light therapy is a safe and likely effective therapy to try.

• AromatherapyAromatherapy uses essential oils. They are massaged into the skin or inhaled asvapors. Aromatherapy has been shown to have an effect on mood in several smallstudies. A small non-randomized pilot trial found that adjunctive aromatherapyallowed for reductions in the dosage of antidepressants compared with usualtherapy. 36 In addition, short-term, but not persistent, mood benefits were found foraromatherapy with citrus oil combined with massage in patients with cancer whowere suffering from depression.37 It was not clear in the latter study how mucheach element, that is massage or oils, contributed to the positive effect.

Reported risks of aromatherapy are minimal and include minor rashes at the site ofapplication or allergic reactions. Aromatherapy can be seen as a reasonable meansfor helping to boost mood in the treatment of depression.

• Music therapyEvidence for the benefits of music therapy is limited and difficult to obtain, as it isalmost impossible to double blind music therapy interventions to compare withplacebo. Variability with genre, volume, individual preferences, and so forth canmake conducting and broadly applying research a challenge, to say the least.However, several trials have been published recently, mostly in older patients,which suggest potential antidepressive effects when music therapy was added tousual care. A dose effect was seen—benefits were more pronounced with longerdurations of treatment.38

The most recent Cochrane Review on music therapy for depression found only fivetrials that met inclusion criteria.39 It concluded that music therapy is well toleratedby people with depression and appears to be associated mostly with improvementsin mood. Risks of music therapy are low; therefore, this intervention can beencouraged as supplemental in those interested.

Personal Development • Positive psychology

In 1998, Seligman established positive psychology. This approach emphasizes using skills and positive attributes to promote cognitive, physical and emotional well-being. The focus is on positive qualities and not merely on weaknesses, illness, or what is wrong.40 A recent review found that positive psychology interventions led to lasting increases in happiness and decreased depressive symptoms.41 A systematic review by Santos and colleagues found 28 studies out of 3,400 that met inclusion criteria.42 They concluded the use of positive psychology strategies (increasing positive emotions; developing personal strengths; and seeking direction, meaning and engagement for the day-to-day life of patients) reduced signs and



symptoms of depression and had the potential to prevent depressive episodes as well.

See the Aspiration, Appreciation, Gratitude and Optimism: Focusing on What’s Going Right clinical tool for more information.

Food and Drink Numerous clinical and observational studies have focused on whether or not there is an association between type of diet and depression onset, but findings of systematic reviews have been inconclusive, likely due to in part to study design challenges. 42-44 Isolating information about specific chemical compounds is a major challenge, and it is perhaps most useful to focus on a healthy overall diet, rather than becoming overly focused on any one chemical compound.

A few studies support a causal relationship between daily excess sucrose and caffeine intake and depression.45,46 A small cohort trial found that eliminating refined sucrose and caffeine from the diets of people experiencing unexplained depression resulted in improvements by one week.47 Symptoms recurred when patients were challenged with these substances again but not when they were given placebo.

A systematic review Sanhueza and colleagues concluded that the only nutrients favorably associated with depression risk were folate, omega-3 fatty acids, and monounsaturated fatty acids.48 Beneficial foods included olive oil and fish. Beneficial diets included those rich in fruits, vegetables, nuts and legumes. These associations differed between men and women, and some were nonlinear.

People who mostly follow a Mediterranean dietary pattern are more likely to ensure ade-quate intake of omega-3 fatty acid from fish, monounsaturated fatty acids from olive oil, and natural folate and other B vitamins from legumes, fruits, nuts, and vegetables. Eating a Mediterranean-style diet has the potential to significantly reduce depression risk.49

• Anti-inflammatory dietUsing data for the 121,700 member cohort group in the Nurse’s Health Study, Lucasand colleagues applied reduced-rank regression analysis to derive a dietary patternthat was associated with selected inflammatory biomarkers. They then testedwhether or not this “inflammatory” diet pattern increased depression risk.50 Theyfound that following this diet pattern did indeed increase depression risk; chronicinflammation does seem to be one mechanism through which diet influencesdepression. Therefore, anti-inflammatory diet approaches should prove helpful fordepression prevention and treatment. At this point, there are no studies to confirmthat this is the case, though several anti-inflammatory diets have been developedand may prove to be beneficial.51 For further details, please see The Anti-Inflammatory Diet clinical tool.



Keep in mind that increasingly research is finding a link between depression and chronic inflammation. Behaviors that reduce inflammation, such as eating an anti-inflammatory diet, taking omega-3 fatty acids, minimizing blood sugar spikes due to simple carbohydrates, and managing stress are worth considering.

• ProbioticsA growing body of literature indicates that intestinal microbial compositioninfluences centrally-mediated systems involved in mood.52 Recent studies suggestthat the intestinal microbial balance may alter the regulation of inflammatoryresponses and, in so doing, may be involved in the modulation of mood.53

Desbonnet and colleagues found that the probiotic bifidobacterium infantisdecreases the impact of separating young animals from their mothers.54 Moreclinical research in surrounding probiotics and depression is warranted. See thePromoting a Healthy Microbiome with Food and Probiotics clinical tool for moreinformation.

Recharge • Sleep

There is growing body of research indicating that sleep and depression have a powerful influence on one another. A 2011 meta-analysis showed that non-depressed people with insomnia (compared to people with no sleep difficulties) have double the risk of developing depression.55 Most recently, a prospective study showed reciprocal effects for major depression and sleep deprivation among adolescents.56 In a study of 166 adolescents diagnosed with depression who were assessed for sleep disturbances while being treated with conservative management, it was found that sleep disturbances were associated with poorer treatment responses.57

Cognitive behavioral therapy (CBT) targeting insomnia led to a significantly greater remission rate in both depression and insomnia.58 See the section on CBT under “Conventional Therapies,” below.

Eight weeks of mindfulness-based cognitive therapy targeting insomnia also improved sleep, anxiety, and depressive symptoms in patients with anxiety.59 For more information see the module, Recharge.

Melatonin and serotonin are closely related. Melatonin is stimulated by lower light levels, and serotonin by higher. Healthy sleep, in appropriately dim light levels, can decrease depression.

Family, Friends, and Co-Workers Social support is a key component of depression treatment. It has been studied in several groups of patients with physical health problems and comorbid depression.60-62 It is important to define what social support is, as social relationships can influence the well-



being of depressed individuals, both positively and negatively. Recent reviews, influenced by self-determination theory, propose that the extent to which social contacts are perceived to fulfill or undermine basic psychological needs determines both the positive or negative health mood effects of those relationships.63 Social support intervention should focus on both strengthening relationships that fulfill basic psychological needs and removal of those that patients see as undermining their well-being.

One review focused on emotion regulation as a key element in the mechanism of action of the benefit of social support.64 The authors suggest that emotional regulation is responsive to interpersonal influences, and that this responsiveness may account for the effects of social support on depression. In other words, interacting with others, and modulating the emotions during those interactions, has a variety of specific effects on emotions. This includes biochemical changes.

Spirit and Soul Spirituality encompasses many aspects of a person’s day-to-day experience, and it can play a significant role in influencing mood. Depression strikes at one’s very sense of meaning and purpose, so exploring how a person can enhance that sense is fundamental. Miller and colleagues reported a 90% decreased risk in major depression, assessed prospectively, in adult offspring of depressed people who reported that religion or spirituality was highly important to them.65 Frequency of church attendance was not significantly related to depression risk.65 Placing a high importance on religion or spirituality is associated with having a thicker cerebral cortex.66 This may confer resilience to the development of depressive illness in individuals at high familial risk for major depression.

For more information, see the Spirit and Soul module.

Power of the Mind67,68 • Mindfulness-based therapies

Initial research on mindfulness looked at its influence on stress reduction. Strong evidence supports the use of mindfulness approaches in this role. A number of mindfulness-based interventions have demonstrated effectiveness for reduction in depression symptoms, including:69,70

o Mindfulness-based stress reduction (MBSR). Originally developed by JonKabat-Zinn at the University of Massachusetts Medical School, MBSR is taught as an eight-week course in health care settings around the country, including many VA facilities. It introduces participants to a variety of forms of meditation. More information about MBSR courses can be found at http://www.umassmed.edu/cfm/Stress-Reduction/. In Veterans, Carlson found improvements in perceived stress, depressive symptoms, and quality of life after a six-week mindfulness course.71 Mindfulness-based stress reduction has been successfully used in the VA environment to treat depression and PTSD while improving quality of life.72

o Mindfulness-based cognitive therapy (MBCT). Developed by Segal,Williams, and Teasdale, MBCT adapts the principles of the MBSR eight-week training course specifically to patients with bouts of recurrent depression.73


http://www.umassmed.edu/cfm/Stress-Reduction/


It is strongly recommended as an adjunctive treatment for unipolar (non-bipolar) depression and has strong evidence supporting its use.74

o Mindfulness-based touch therapy. Mindfulness-based touch therapyinvolves the use of a passive body intervention in combination with mindfulness as an active meditative discipline. Stotter and collaborators conducted the first prospective, randomized, single blinded study, which included 28 patients who were on antidepressants throughout the study.75 Fourteen patients were assigned to the test group, and fourteen were in a control group, where they received mindfulness-based stress reduction training without the touch component. Using the Hamilton Rating Scale for Depression (HAMD) to assess symptoms, researchers found reductions of depressed mood, feelings of guilt, and suicidal thoughts. They found improvements in sleep maintenance and motivation. Feelings of anxiety decreased at both the psychological and somatic levels, and there was a decrease in general somatic symptoms as well. These promising findings warrant further controlled studies with larger populations.

Approaches based on mindful awareness, including mindfulness-based stress reduction and mindfulness-based cognitive therapy, are well-supported by the research for the treatment of depressive illness.

o Compassion training. A recent study suggested that compassionate mindtraining could lead to significant reductions in depression, anxiety, self-criticism, and shame.76 The function of a part of the brain known as theamygdala is impaired in a number of disorders, including depression.77

Functional MRI studies of the effect of mindfulness on the amygdala foundthat after an eight-week course of cognitively-based compassion training,there was an increase in right amygdala response to negative images. Thischange in the amygdala was significantly correlated with a decrease indepression scores.78

• HypnotherapyHypnotherapy has been around for more than a century, and its role in treatingdepression has been investigated for the past 20 years.79 A recent meta-analysisbased on a small number of studies suggested that hypnotherapy is a viable non-pharmacologic intervention for addressing symptoms of depression. At this point,there is a need for more trials that tease out differences in efficacy between specifictypes of hypnotherapy.80

In the general population, hypnotherapy appears to have minimal adverse effects,but it must be used in military populations only under the guidance of those withspecific credentialing. Its success depends largely on the engagement of the patient.Therapists must have skill in determining who is or is not an appropriatehypnotherapy candidate, as past traumatic experiences for some people may bereactivated through entering a trance state. Dobbin found self-hypnosis to be a



preferred mode of treatment of depression in a primary care setting and comparable to medications and CBT in a partially randomized preference study design.81

o Cognitive hypnotherapy (CH). Alladin and collaborators combinedhypnotherapy and CBT to create cognitive hypnotherapy, which became the focus of an evidence-based handbook they developed.82 CH is thought to achieve benefits through six means: 1) altering depressive mood, 2) establishing positive expectancy, 3) countering depressive rumination, 4) developing anti-depressive neuro-pathways, 5) accessing and restricting unconscious cognitive distortions, and 6) behavioral activation.

• RelaxationA 2008 Cochrane review concluded that in general, “Relaxation techniques weremore effective at reducing self-rated depressive symptoms than no or minimaltreatment, but not as effective as psychological treatment.”83

• PsychotherapyPsychotherapy takes many forms, some of which are more widely used in healthcare settings than others. Various types of psychotherapy are featured in the nextsection on conventional approaches to depression. It should be recognized,however, that some forms are much more widely used than others. Of course,regardless of which section they are put in in this overview, all of these therapiesinvoke “The Power of the Mind” in various ways.

Conventional Approaches to Depression

Psychotherapy-based approaches There are several modalities of psychotherapy with clinical evidence supporting their use for depression. They have minimal side effects and long-lasting benefits. The modalities that have been studied most and found to be most effective include

• Cognitive-behavioral therapy• Interpersonal psychotherapy• Psychodynamic therapy• Problem-solving therapy, in individual and group formats.

Others with growing research and evidence to support their use include hypnotherapy, cognitive hypnotherapy, mindfulness-based cognitive therapy (featured in the Power of the Mind Section, above) as well as acceptance and commitment therapy, and marital therapy.

The American Psychiatric Association (APA) considers psychotherapy to be a first-line therapeutic option for patients with mild to moderate major depressive disorder. It can be used alone or, in cases of severe major depressive disorder, as combination therapy with other modalities. Using it in combination with medications appears to have superior efficacy to use of medications alone in all levels of depression severity. The APA has a



number of patient friendly, informative videos and documents on psychotherapy available at http://www.apa.org/helpcenter/psychotherapy-works.aspx. Factors to consider in choosing any of the psychotherapy modalities include the following:

• Availability of trained clinicians• Patient preference• Psychosocial context• Prior beneficial response to psychotherapy• The presence or absence of significant psychosocial stressors or interpersonal

difficulties• Intrapsychic conflict• Presence of Axis II disorders (e.g., personality disorders)• Stage, chronicity, and severity of major depressive episodes.

Several psychotherapies practiced within the VA are described below, with a discussion of the state of the evidence supporting (or not supporting) their use. The list is by no means comprehensive, and some approaches are much more widely available than others.

As a clinician, you are encouraged to know the various forms of psychotherapy available to people with depression so that you can be an effective matchmaker between a given individual and a given therapy (or therapist). The “fit” between Veteran and therapist may be as important as the therapy itself.

• Cognitive behavioral therapy (CBT)CBT is the most-studied psychotherapeutic approach to depression. The clinicianguides the patient in identifying and replacing negative patterns of thinking withmore positive and realistic approaches. CBT includes education about therelationship between thoughts, behaviors, and emotions. Patients are taughtbehaviors that serve as more productive responses to challenging circumstances orfeelings. CBT is considered a short-term therapy; the length is usually 10 - 20sessions. For more information, see the National Alliance on Mental Illness (NAMI)websiteat http://www.nami.org/Content/NavigationMenu/Inform_Yourself/About_Mental_Illness/About_Treatments_and_Supports/Cognitive_Behavioral_Therapy1.htm.

CBT decreases the risk of relapse even after formal treatment sessions arecompleted. Continuing CBT in the maintenance phase further decreases this risk. 84

Hollon and colleagues reviewed evidence from 1980 to 2004 and found that CBTcan be as effective as medications in the acute treatment of depressed outpatients. 85

• Interpersonal Therapy (IPT)Like CBT, IPT is another form of psychotherapy. Developed in the 1970s, IPT isbased on the idea that many psychological symptoms arise through interpersonaldistress. Treatment usually is offered for 12-16 weeks and focuses on exploringrelationships and how they influence –and are influenced by – one’s behavior andmood.


http://www.apa.org/helpcenter/psychotherapy-works.aspx

http://www.nami.org/Content/NavigationMenu/Inform_Yourself/About_Mental_Illness/About_Treatments_and_Supports/Cognitive_Behavioral_Therapy1.htm

http://www.nami.org/Content/NavigationMenu/Inform_Yourself/About_Mental_Illness/About_Treatments_and_Supports/Cognitive_Behavioral_Therapy1.htm


IPT’s efficacy has been shown in randomized controlled trials.86,87 IPT can be as effective as medications in the acute treatment of depressed outpatients.85 The degree to which patient and therapist can resolve the interpersonal crisis on which IPT focuses (e.g., a role transition) appears to correlate with symptomatic improvement.88 For more information, see the website for the International Society for Interpersonal Psychotherapy at http://interpersonalpsychotherapy.org/about-ipt/.

• Psychodynamic Therapy (PT)PT is defined differently in various studies. Also known as insight-oriented therapy,it focuses on gaining insight into unconscious processes and how they manifest inthe way a person behaves.89 PT has been used widely in clinical practice for thetreatment of depressive disorders, and it is preferred by many patients over otherapproaches.90 Recent meta-analyses suggest that both short-term and long-termpsychodynamic psychotherapy are effective for depressed patients.91,92 For moreinformation, see the GoodTherapy.org Websiteat http://www.goodtherapy.org/psychodynamic.html.

• Marital therapy (MT)Marital therapy, or couples therapy, involves working with both depressedindividuals and their significant others. MT showed comparable efficacy toindividual psychotherapy for the treatment of depression in a 2006 meta-analysis.93

Several reviews have found that marital therapy is effective for treating depressivesymptoms and reducing risk for relapse.94,95 Some individual studies havesuggested that the efficacy of marital therapy may depend on whether or not maritalproblems are present.96

A lower dropout rate and greater improvement in subjective symptoms ofdepression, at no greater cost, were found for a couples therapy group incomparison to medications alone.97 Patients with major depressive disorderadmitted to inpatient units were more likely to improve if family therapy was partof their treatment. They had significant reductions in interviewer-rated depressionand suicidal ideation.98

• Problem-Solving Therapy (PST)PST is a brief intervention, done in four to eight sessions. A therapist reviews theproblems a person is experiencing in his or her life and then focuses on solving oneor more of those problems to demonstrate more effective problem-solvingtechniques. PST has shown modest improvement in study participants with milddepressive symptoms; most studies have been done in geriatric populations. Forexample, Alexopoulos and colleagues reported that 12 sessions of problem-solvingtherapy were superior to supportive psychotherapy for this population with majordepressive disorder and executive dysfunction.99 For more information, see theUniversity of Auckland PST websiteat http://www.problemsolvingtherapy.ac.nz/index.php?p=steps.


http://interpersonalpsychotherapy.org/about-ipt/

http://interpersonalpsychotherapy.org/about-ipt/

http://www.goodtherapy.org/psychodynamic.html

http://www.problemsolvingtherapy.ac.nz/index.php?p=steps


• Acceptance and Commitment Therapy (ACT)This approach also incorporates mindful awareness to prevent depression relapse.It is classed in this document as a “conventional therapy” because it is rapidlygaining popularity in VA facilities. Research has shown that ACT has powerfulpositive effects on depression, as well as many other illnesses.100

ACT invokes mindfulness techniques, acceptance, and commitment/behaviorchange strategies to enhance a person’s psychological flexibility. A person learns tofocus effectively in the present moment to address any given situation that arises.People are encouraged to “make healthy contact” with thoughts, memories, feelings,and sensations they have avoided in the past. To learn more,see http://contextualscience.org/act.

Pharmaceutical approaches According to current APA guidelines, medication is recommended as one of the initial treatment choices for patients with mild to moderate major depressive disorder and should be offered for those with severe major depressive disorder.101 Effectiveness of antidepressant medications is generally comparable between classes and within classes of medications. Therefore, there are several elements to take into consideration in choosing the initial medication. These include medication response in prior episodes, expected side effects, safety or tolerability of these side effects for the individual patient, pharmacological properties of the medication including other drug interactions, cost, and patient preference.

Many studies demonstrate efficacy for various pharmacological and psychological therapies as first-line treatments; however, the degree to which they are effective is, in many studies, disappointing. This is especially true in the treatment of depression in its mild to moderate forms.9

Clinicians often find it challenging to know how to make individualized medication choices; for more information on personalizing medication remedies, see the following websites:

• Psi-World. http://www.psy-world.com/choosing.htm• Agency for Healthcare Research and Quality. “Choosing Antidepressants for Adults,”

at http://effectivehealthcare.ahrq.gov/repFiles/AntidepressantsClinicianGuide.pdf.

Each of the following medication classes has been shown to have efficacy; that is, they are superior to placebo in controlled studies and meta-analyses.101

• Selective serotonin reuptake inhibitors (SSRIs)SSRIs in use for depression include fluoxetine, sertraline, paroxetine, fluvoxamine,citalopram, and escitalopram. They generally have fewer side effects andinteractions than other classes of antidepressants. Most common side effectsinclude gastrointestinal discomfort, activation/insomnia, sexual side effects,


http://contextualscience.org/act

http://www.psy-world.com/choosing.htm

http://effectivehealthcare.ahrq.gov/repFiles/AntidepressantsClinicianGuide.pdf


serotonin syndrome, interactions with coagulation, and discontinuation syndrome.102

• Tricyclic antidepressants (TCAs)TCAs most often used for depression include amitriptyline, nortriptyline,protriptyline, imipramine, desipramine, doxepin, and trimipramine. They areconsidered in clinical practice to be especially beneficial in a subset of patients withmelancholia or more severe depression. Most significant side effects includecardiovascular, anticholinergic, sedation, weight gain, falls.102

• Serotonin norepinephrine reuptake inhibitors (SNRIs)SNRIs in use for depression include venlafaxine, desvenlafaxine and duloxetine.They have a similar side effect profile to SSRIs, but in addition, they havenoradrenergic activity; this is especially true for venlafaxine when dosed above 150milligrams. Adverse noradrenergic effects include increased pulse rate, dilatedpupils, dry mouth, excessive sweating, and constipation.103

• Monoamine oxidase inhibitors (MAOIs)MAOIs in use for depression include phenelzine, tranylcypromine, isocarboxazid,moclobemide, and a transdermally delivered formulation of selegiline. Thesecompounds have been shown to be particularly effective in treating depressedpatients with atypical features, such as reactive moods, reverse neurovegetativesymptoms, and sensitivity to rejection.104 Special attention needs to be placed hereto diet and medication interactions; tyramine or other vasoactive amines in foodsor medications may produce severe side effects, such as hypertensive crisis.105

• Other antidepressantso Bupropion. Bupropion is classified as a norepinephrine and dopamine

reuptake inhibitor, with a relatively weak dopamine action. Its mechanism ofaction remains unclear. Side effects include headaches, tremors, andseizures.106 It should be avoided in patients with anorexia nervosa orbulimia, and it does not cause sexual side effects.

o Mirtazapine. Mirtazapine is not a reuptake inhibitor. It is a tetracyclicmolecule and is thought to work through noradrenergic and serotonergicmechanisms. Most common side effects include dry mouth, sedation, andweight gain, which is ideal in patients who present with symptoms ofinsomnia and decreased appetite.107 Rarely, it can increase cholesterol andagranulocytosis.

o Trazodone and Nefazodone. Trazodone is mostly used in low doses as asedative-hypnotic mostly due to its most common side effect, sedation.108

However, there is little evidence to support its use for sleep. It has similarefficacy to others in its group in the treatment of depression.107 Nefazodoneis similar to trazodone, but because it is primarily metabolized in the liver, ithas been associated with rare but potentially fatal liver failure. It is rarelyused.



Other conventional approaches • Electroconvulsive therapy (ECT)

ECT has the highest response and remission rates of any form of treatment for depression, with an improvement up to 70%–90% of those treated.109 ECT should be contemplated in patients who fail to respond to medication and/or psychotherapy interventions.110 It may be first line treatment in patients with severe major depression when a fast antidepressant response is desired and when any of the following elements are present: suicide risk, catatonia, psychotic features, severe illness, or food refusal with nutritional compromise.111

The following are classed as conventional therapies not because they are widely used, but because they have FDA approval.

• Transcranial magnetic stimulation (TMS)TMS aims to produce electrical stimulation of superficial cortical neurons at leftdorsolateral prefrontal cortex through the use of a magnetic coil that generatesrapidly alternating magnetic fields. These fields are similar in strength to thoseused for MRI’s.112 TMS has been approved by the FDA to treat depression inpatients who have not had an acceptable response to at least one antidepressanttrial in the current episode of illness. Most, but not all, meta-analyses have foundsmall to moderate benefits of TMS in depression.113 Efficacy is either less than orsimilar to that of ECT. TMS is well tolerated; most common side effects are transientscalp discomfort and headaches.114

• Vagus nerve stimulation (VNS)VNS involves implanting a device that sends electrical pulses to the brain. It hasbeen found useful in chronic depression, but not in the acute phase.115 In 2005,based on clinical trial data, the FDA approved the use of VNS as an adjunctivetherapy for treatment resistant depression in adult patients who have failed four ormore medications. VNS can safely be combined with ECT in cases of acute relapse.The cost is very high--above $40,000 for a day of surgery plus adjustments.116

Complementary Approaches to Depression

Acupuncture Acupuncture is a part of traditional Chinese medicine (TCM) that promotes the restoration and maintenance of health through the stimulation of various points on the body. In acupuncture, points are stimulated by needles, electricity-augmented needles, and lasers. For more general information, see the clinical tool, Acupuncture and Traditional Chinese Medicine. There are also needleless approaches. In TCM, one of the proposed etiologies of mental disorders is internal damage caused by the deregulation of the six emotions: anger, worry, contemplation (thinking), sorrow (grief), fear, and shock.117 When any of these emotions is in excess, dysfunction can arise, resulting in depression.



Many mechanisms of action have been proposed for acupuncture; it is thought to influence mood through the modulation of the neuroendocrine and immune systems, regulating levels of 5-HT, norepinephrine, dopamine, endorphins, and/or glucocorticoids and stimulating responses in the hypothalamus and hippocampus.118

Conclusions of various reviews of acupuncture trials are mixed, but favorable overall. A 2010 Cochrane review found insufficient evidence to recommend using acupuncture for depression, based on 30 studies identified as meeting inclusion criteria (n=2,812).119 It was noted that a subgroup of 94 participants in three studies who had depression as a comorbidity did have a reduction of depression119 in comparison with the use of SSRIs. A meta-analysis of 35 RCTs conducted by Zhang and colleagues identified that acupuncture is a safe and effective treatment for major depressive disorder and post-stroke depression.120 A meta-analysis of eight RCTs by Wang and colleagues concluded that acupuncture can significantly reduce the severity of depression.121 Another study found that a combination of acupuncture plus low-dose fluoxetine was as effective for depression as the recommended dose of fluoxetine, with the lower dose being beneficial for people with intolerable side effects. 122 Increasing numbers of studies focus on whether or not acupuncture can decrease medication side effects; for example, a Cochrane review found that stimulation of the P6 acupuncture point was more effective than antiemetic medication for managing medication-related nausea and vomiting.123 Future studies will evaluate whether similar effects can occur with decreasing side effects of antidepressants.

A 2011 “systematic review of systematic reviews” looked at eight reviews that included 71 primary studies. Five of the reviews arrived at positive conclusions and three did not.124 The positive studies were all done in China. The reviewers concluded that the effectiveness of acupuncture as a treatment for depression remains unproven. Adverse events are rare and include soreness, pain, bruising, and mild bleeding at the needle site.117

The mixed results for studies of acupuncture for treating depression are likely due to four factors:

1. The particular challenge of inadequate placebo interventions2. Variation in definitions/diagnostic criteria of depression; most studies have been

done with diagnostic criteria that differ from DSM-IV TR/V3. Considerable disparities in the way that acupuncture is routinely practiced,

especially in the West4. Most of the evidence available is published in Chinese-language journals.

Studies are increasingly taking these challenges into account. For example, a recent, well designed, non-blinded (blinding is difficult in acupuncture studies) randomized control trial published in English in 2013 used well-validated inventories to assess depression (SDS, MADRS) and personality disorders (MMPI).125 Participants were assigned to one of two groups. One group was treated with electro-acupuncture and the other one treated with paroxetine. Both interventions were equally effective in decreasing severity of depression after 24 weeks. Acupuncture was more effective in decreasing measures on the MMPI subscale of paranoia and social introversion. This study documents in substantial



detail the acupuncture technique used and the practitioner’s experience, allowing for ease of replication and clinical use.

Given the above information, acupuncture seems to have a growing body of evidence of positive clinical use as monotherapy, as augmentation for treatment of symptoms of depression, and for treatment of side effects of medication. Not having a well-trained acupuncturist available might perhaps be the main obstacle to recommending this intervention. Most therapists will note that multiple sessions are needed to treat chronic conditions. For example, a patient may be seen for 30-60 minutes a week for three months or more.

Homeopathy Evidence for the effectiveness of homeopathy in depression is limited, due to a lack of clinical trials of high quality or insufficient numbers of participants.126 Over 50 single case reports/studies mostly serve to indicate the range of remedies employed in patients whose symptoms include depression. Homeopathic medicines rarely provoke adverse effects and when this occurs, they are relatively rare, mild and transient. Still, it is difficult to justify using homeopathy based on the current state of the research. See the Homeopathy clinical tool for more information.

Massage Massage therapy, defined as the intentional and systematic hand motion practiced on soft tissues of the body, has been found to decrease stress and muscle tension, increase pain threshold, and stimulate positive emotions.127

Classical European “Swedish” massage has been the most researched for depression. Rationale for investigating the role of massage in depression stems from findings that massage leads to changes in electroencephalogram patterns. A symmetrical or left frontal pattern has been found, which is associated with happy affect. Massage also stimulates facial expressions and increases vagal activity, which has been shown to reduce depressed affect.128

A multicenter randomized controlled trial found aromatherapy massage to be associated with clinically important benefit for depression symptoms for up to two weeks in patients with cancer.37 A recent meta-analysis including 17 studies containing 786 persons concluded that massage therapy is significantly associated with alleviation of depressive symptoms.129

Given this information, massage should be seen as an effective ancillary treatment and likely a promoter of maintenance of remission. There is no evidence to support its being used alone as a first-line therapy. See the Massage Therapy clinical tool for more general information.



Dietary supplements: non-botanicals

Note: Please see the module on Dietary Supplements for more information about how to determine whether or not a specific supplement is appropriate for a given individual. Supplements are not regulated with the same degree of oversight as medications, and it is important that clinicians keep this in mind. Products vary greatly in terms of accuracy of labeling, presence of adulterants, and the legitimacy of claims made by the manufacturer.

Omega-3’s, folate, magnesium, and zinc are on the VA formulary. The others listed below are not; Veterans typically have to pay for them out of pocket.

• Omega-3 fatty acidsPeople with depression have been found to have a deficiency of omega-3 fatty acidsor an imbalance in the ratio of omega-6 and omega-3 fatty acids.130 Synapticmembrane fluidity is significantly determined by cholesterol and dietarypolyunsaturated fat levels. Therefore, optimal proportion of these elements ispostulated to have an impact in depression.131 A clinically relevant antidepressanteffect was demonstrated recently in a post hoc analysis of depressed patients whosupplemented their diets with omega-3 fatty acids (DHA/EPA) in addition to takingtheir conventional antidepressants.132 Interestingly, rat models, rich in omega-3exhibit increased hippocampal neurogenesis.131 Furthermore, an elevated ratio ofomega-6 to omega-3 fatty acids predicts depression development followinginterferon-alpha treatment.133 A low omega-3 index in late pregnancy wasassociated with higher depression scores three months postpartum.134

• S-Adenosyl methionine (SAMe)Pronounced “Sammy,” S-adenosyl methionine is an amino acid derivative that isfound in virtually all body tissues and fluids. It plays a role in over 100 biochemicalreactions, most of which involve the transfer of methyl groups. SAMe is importantfor the synthesis and metabolism of proteins, nucleic acids, neurotransmitters,hormones, and many other compounds. Deficiencies of B12 and folate can be linkedto low levels of SAMe in the nervous system. SAMe’s mechanism of action isunknown, but higher SAMe levels have been linked to increased serotonin turnoverand elevated dopamine and norepinephrine levels. Severely depressed patientsoften have low levels of SAMe in the spinal fluid, and SAMe supplementation cannormalize them.135

SAMe is often used for treatment of both depression and also pain. Some peoplerefer to it as the supplement equivalent of duloxetine (Cymbalta). SAMesignificantly improves symptoms of depression.136 SAMe tends to have a more rapidonset than many antidepressants, so some clinicians may use it as a stopgap whilewaiting for drug therapies to take effect.137 It can significantly increase remissionrates in depressed patients who do not respond to medications.133 Seven peoplewith non-responsive depression need to be treated with SAMe (dose of 400-800milligrams) to have one additional remission.



SAMe tends to be quite safe. Side effects can occur with high doses, such as nausea, vomiting, diarrhea, constipation, nervousness, dry mouth, headache, but these tend to be minimal in comparison with side effects from antidepressants.136 Dosing ranges from 400 milligrams to 1600 milligrams daily divided into two doses. SAMe’s biggest drawback is that it can be quite expensive to purchase over the counter.

• ZincResearch suggests potential benefits of zinc supplementation for depression, eitheras a stand-alone therapy or as an adjunct to drug therapy. However, a recentsystematic review of randomized controlled trials found methodological limitationsin existing studies and recommended further research.138

• Tryptophan and 5-hydroxytryptophan (5-HTP)A Cochrane review found that in 2 out of 108 trials, tryptophan and 5-HTP werebetter than placebo at alleviating depression. Further research is warranted toevaluate efficacy and safety, as there is a possible association between thesesubstances and the potentially fatal eosinophilia-myalgia syndrome.139 Mostauthorities agree that the occurrence of this syndrome was largely attributable tocontamination of a specific batch of supplements made by one company.

• InositolA meta-analysis identified two depression studies where inositol had marginallymore responders in depression than placebo (p = 0.06).140 However, inositol alsomarginally caused gastrointestinal upset compared with placebo (p = 0.06). Inositolsupplementation may have limited benefit for depression.

• FolateFolate is known to be linked to serotonin metabolism,141 mostly due to its role inmethylation reactions that form the rate-limiting step in the production ofneurotransmitters like serotonin.142 Trials identified in a 2004 Cochrane review didnot find evidence of adverse effects for folate. Limited evidence suggests folate mayhave a potential role as an adjunct to other treatments for depression.143

• MagnesiumThe use of magnesium to treat depression dates back 100 years ago whenmagnesium sulfate injected hypodermically was found to be helpful in patients withagitated depression.144 Magnesium’s mechanism of action is unknown, but it may berelated to the glutamatergic mechanism, since magnesium acts as physiologicalNMDA receptor antagonist.145 A systematic review published in 2013 suggests thatmagnesium may be effective in the treatment of depression, but evidence is limitedoverall.146 Oral magnesium supplementation may prevent depression and might beused as an adjunctive therapy, but further research is needed.



Dietary supplements: botanicals Recently, there has been a 50% increase in the number of studies of botanicals for depression,147 including a number of epigenetic studies.148 Surveys indicate that 44% - 54% of depressed patients have used herbal remedies in the past 12 months.149 Most research focuses on the use of botanicals for mild to moderate depression.

Botanicals differ from medications, most notably because they are polyvalent. That is, they contain multiple chemicals that may contribute to therapeutic benefit that may work in synergy to bring about a therapeutic effect. This is thought to lead to a lower rate of side effects but also to difficulty in standardization. Since depressive disorders tend to be associated with comorbid anxiety and other psychiatric disorders, the use of polypharmacy in psychiatry is increasing; antipsychotics are often used along with antidepressants. Botanicals may, in some ways, have a similar effect; in both cases, the use of multiple different psychoactive compounds can be beneficial.

• St. John’s wort (Hypericum perforatum)This supplement is typically dosed at 300 milligrams three times a day standardizedto between 3% and 6% hyperforin and not less than 6% flavonoids for depression.Outcomes in many studies include reduction in scores on the Hamilton Rating Scalefor Depression (HAMD),150 lower relapse rate, and longer time to relapse comparedto placebo groups.151 Three studies showed an effect of St John’s wort that wascomparable with pharmaceuticals.

If anyone ever asks what botanical has the most interactions with medications, it isSt. John’s wort. It alters the cytochrome P-450 3A4 detoxification pathway. Cautionshould be used in taking St. John’s wort with antiretrovirals, warfarin, cyclosporine,or oral contraceptives, among other medications. Because it is known to be a mildMAO-I, similar dietary and medication interaction precautions should be taken aswith a MAO-I drug. St. John’s wort is not just an herbal SSRI; it seems to affectmultiple different biochemical pathways.

• Roseroot (Rhodiola rosea)Roseroot significantly improved HAMD scores as well as insomnia, somatization,and emotional instability subscale outcome measures at doses of 340 milligramsdaily of standardized extracts.152

• Saffron (Crocus sativus)Saffron demonstrated significant improvement for depression over placebo onHAMD scores.153 Petals and stamen were used in doses of 30 milligrams daily.Equivalent therapeutic response was demonstrated for saffron, imipramine 100milligrams daily, and fluoxetine at 20 milligrams BID on the HAMD.

• Lavender (Lavendula spp.)Lavender showed a synergistic effect to imipramine; adding it to imipraminetherapy was more effective in reducing HAMD rated depression than imipramine



alone.154 It was dosed as a tincture (1:5 50% alcohol, 60 drops daily). Imipramine alone was more effective than lavender alone. The mechanism of action is likely GABA modulation.

• Borage (Echium amoenum)Borage showed limited benefit for depression compared to placebo. There was aninitial decrease in HAMD scores, but the benefit was not maintained after week sixof dosing at 375 milligrams daily.155

• Ginkgo (Ginkgo biloba)Ginkgo has been found to be useful in treating older patients (51-78 years of age)with depression related to organic brain dysfunction, especially when they haveproven to be unresponsive to standard drug treatment.156 Dosing used indepression studies was 40 milligrams to 80 milligrams three times daily of a 50:1extract standardized to contain 24% ginkgo-flavone glycosides. Due to potentialanticoagulation effects, ginkgo should not be used by anyone during the periodsbefore or after surgery or labor and delivery, and it should be used with caution inpeople with bleeding problems. It may interact with blood thinners, calciumchannel blockers, aminoglycoside antibiotics, anticonvulsants, and neuroleptics.

Many supplements show potential benefit, but they must be used with care. St. John’s wort, in particular, is involved in many supplement-drug interactions. In general, it is best not to recommend herbal remedies for depression at the same time as one is taking antidepressant medications.

The Big Picture: A Summary of Levels of Evidence

Because there are so many potential recommendations one could make when addressing depression from a Whole Health approach, a summary of the evidence for the ones featured in this overview is offered below.

One of the most effective ways to rate evidence is the Strength of Recommendation Taxonomy, or the SORT criteria. It is simple, and it takes clinical relevance of the research into account. A simplified summary follows. A more extensive review can be found at http://www.aafp.org/afp/20040201/548.html.157

• Grade A—Based on consistent, good quality, patient oriented evidence.Systematic review or meta-analysis showing benefit, Cochrane review with clear recommendation; high-quality patient-oriented randomized controlled trial.

• Grade B—Based on inconsistent or limited-quality patient oriented evidence.• Grade C—Based on consensus, usual practice, opinion, disease-oriented

evidence, or case series. Topics where more research is needed to draw a finalconclusion are also categorized here.


http://www.aafp.org/afp/20040201/548.html


Recommendations with Grade A evidence: • A healthy therapeutic relationship• Psychotherapy approaches (cognitive behavioral therapy, interpersonal

psychotherapy, psychodynamic therapy, problem-solving therapy, marital therapy)• Medications (but depends a great deal on the specific medication and the specific

research being cited)• Electroconvulsive therapy (severe major depression)• Positive psychology• MBCT for relapse prevention• Ultraviolet light therapy for seasonal symptoms• Eating foods with folate, omega-3 fatty acids, and monounsaturated fats• Dietary supplements

o S-adenosyl L-methionine (SAMe)o St. John’s wort (but drug interactions and overall safety must be considered).

Recommendations with Grade B evidence: • Other types of psychotherapy (acceptance and commitment therapy, behavioral

activation) • Mindfulness meditation• Anti-inflammation diets• Acupuncture (depending on which meta-analyses one reads; benefits include

augmenting medication benefits)• Music therapy• Hypnotherapy (offered by credentialed professional)• Relaxation therapies• Adequate sleep• Social support• Decreasing dietary sugar• Dietary supplements

o Borageo Inositolo Lavendero Methylfolate (as an adjunctive therapy to SSRIs)o Omega-3 fatty acids (as supplements versus in the diet)o Roseroot (Rhodiola)o Saffron

• Transcranial magnetic stimulation• Vagus nerve stimulation

Recommendations with Grade C evidence (more research needed): • Probiotics• Tai chi and yoga• Aromatherapy• Sense of meaning and purpose (spirituality)



• Mindfulness-based touch therapy• Cognitively-based compassion training• Homeopathy• Massage• Supplements

o 5-hydroxytryptophano Ginkgoo Magnesium

Frank’s Personalized Health Plan

Based on the research summarized above, a Personalized Health Plan was created for Frank. The plan was somewhat detailed for Frank, but of course the length of a PHP will vary according to what is practical based on the available time of Frank’s team and Frank’s willingness to make changes. A more detailed plan could look like the one below.

VHA Office of Patient Centered Care and Cultural TransformationPage 29 of 42


Your Personal Health Plan Mission: To bring the love and joy of my relationship with my grandchildren into my everyday life in more consistent ways.Brief Summary of the Plan:

You agree that you are depressed, but you don’t want to take pills. You are willing to look at other ways to deal with your depression and are very motivated to be at your best for your grandchildren. There are times when you feel happy and those times revolve around your family, particularly your grandchildren. Rather than treat this depression with pills, we agree to “dial up the joy.” You have agreed to work with an Integrative Health Coach on our team at the clinic.

Overall Health Goals:

Develop a plan to "dial up the joy" and improve my mood.

Mindful Awareness:

Practice paying more attention to the signs and signals from your body that you are starting to feel sad. Check in with your body and mind several times a day, noting how you are feeling.

Dear Frank,

It was a pleasure meeting with you last week at the VA Medical Center. You sought consultation for developing a plan for your overall health and well-being, specifically to develop a comprehensive treatment plan for your diagnosis of depression.

We are committed to partnering with you to provide comprehensive treatment for your diagnosis of depression while optimizing your well-being throughout the process. Included in this letter is your Personalized Health Plan, which represents your personal values, priorities, and vision for your health based on your responses during your initial personal health planning visit.

In partnership with you, your health care team has developed team recommendations to support you on the road to optimal health and well-being. All members of your health care team can now refer to this plan as your overall strategy for your health, and ensure that our treatment plans align with your priorities and with each other.

Sincerely,

Your Whole Health Team

Pers

onal

Hea

lth P

lan

(PHP

)



Proactive Self Care

Working Your Body Pay attention to the early signs of feeling heavy or blue, and go for a walk, at least around the block. Consider other physical activities for the future.

Surroundings Ask the family to send pictures of the grandchildren so you can place them around the house and see their faces frequently.

Personal Development

Explore opportunities for continued learning or volunteer work, like perhaps as a VA volunteer.

Food and Drink Keep a food, drink, and mood diary and notice if there is a connection between eating and your mood. Join the MOVE program.

Recharge Develop a sleep hygiene routine that includes relaxation techniques. Read the pamphlet “Your Guide to Healthy Sleep.”

Family, Friends and Co-Workers

Talk to your son and daughter and their spouses about wanting to find more regular avenues to connect with your grandchildren.

Spirit and Soul Look for ways to increase connections with your grandchildren, which seem to fuel your spiritual well-being.

Support Team

Principal Professionals Personal

• Primary careclinician

• Integrative healthcoach

• Children• Grandchildren• Friends

Professional Care

Prevention Medications/ Supplements

Testing/ Treatments Referrals Skill building and

education • Up to date • Prescribed

medications• Dietary

supplements

• None at thistime

• Integrativehealth coach (ifavailable)

• MOVE program

• Nutrition• Relaxation and

breathingtechniques

Follow-Up (next steps)

• Telephone visit with primary care practitioner in one week to discuss progress and otherneeds

• Schedule integrative health coaching sessions to work on self-care portion of the plan• Participate in MOVE program

Pers

onal

Hea

lth P

lan

(PHP

)



How Frank Is Doing Now

Frank has seen his integrative health coach four times now and is feeling much happier. He learned the skill of paying attention and noticing the early signs and signals of feeling heavy. That gave him an opportunity to take action before he became sad and depressed. His family loved the idea of helping him connect more to the grandchildren. They set up a Skype account for him and scheduled a time every day (alternating between the families) for him to Skype or talk on the phone with his grandkids. He also learned how to get on the older kids’ Facebook pages. He loved this.

Keeping a food diary helped him see that he often used food to feel better, particularly sweets. If it was after 5:00 p.m., he might have an alcoholic drink or two. He noticed that eating sweets or drinking alcohol made him feel better at first and then worse. And feeling worse would then result in him eating or drinking even more. He decided that when he found himself having those cravings, he would get up and walk around the block. When he returned, if he still wanted the food or drink, he could have it, but more than half of the time he found he no longer wanted it. This fit nicely with the MOVE program, and he found the support through that program very helpful. He was surprised to find that his sleep was improved as well and found even more benefit with the relaxation techniques he learned to use prior to sleep and any time he awakes. Frank decided to become a VA volunteer and will start in two months when he feels more comfortable with his new routines. Frank’s most recent PHQ-9 score was a “5”, which is on the borderline between minimal and mild depression and an improvement since the last score.

Depression Clinical Tools • Depression• Mind-Body Approaches and Depression• Dietary Supplements and Mood

Additional Resources Patient Education Programs Website

Behavioral Health Lab https://vaww.visn4.portal.va.gov/networks/BHL/default.aspx

Translating Initiatives for Depression into Effective Solutions (TIDES)

http://vaww.portal.gla.med.va.gov/sites/Research/HSRD/ClinicalPart/default.aspx

VISN 2 Center for Integrated Healthcare http://www.mirecc.va.gov/cih-visn2/

Provider Education Programs Website

Behavioral Health Lab https://vaww.visn4.portal.va.gov/networks/BHL/default.aspx

Translating Initiatives for Depression into Effective Solutions (TIDES)

http://vaww.port al.gla.med.va.gov/sites/Research/HSRD/ClinicalPart/default.aspx


https://vaww.visn4.portal.va.gov/networks/BHL/default.aspx




http://www.mirecc.va.gov/cih-visn2/




University of Massachusetts Center for Integrated Primary Care

http://www.umassmed.edu/CIPC/Who-We-Are/Our-Mission/

VA-DoD Guidelines for the Management of Major Depressive

Disorder (2009)

http://www.healthquality.va.gov/Major_Depressive_Disorder_MDD_Clinical_Practice_Guideline.asp

VA Primary Care-Mental Health Integration Initiative:

http://vhaishappv11:32675/sites/omh/PCMHI/Pages/default.aspx

See also VA national Rollouts for Interpersonal Psychotherapy (IPT), CBT for Depression, and Problem Solving Therapy (PST)

This educational overview was written by Mario Salguero, MD, PhD, Voluntary Assistant Clinical Professor in the Department of Psychiatry, University of California-San Diego School of Medicine. Dr. Salguero has a private practice as an integrative psychiatrist at La Jolla Village Professional Center, La Jolla, California.

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Whole Health: Change the Conversation Website

Interested in learning more about Whole Health? Browse our website for information on personal and professional care.

http://projects.hsl.wisc.edu/SERVICE/index.php








http://www.nami.org/Content/navigationMenu/Mental_Illnesses/Depression/Depression_Veterans_Factsheet_2009.pdf

http://www.nami.org/Content/navigationMenu/Mental_Illnesses/Depression/Depression_Veterans_Factsheet_2009.pdf

http://shfwire.com/files/pdfs/2011CAM_FinalReport.pdf

http://projects.hsl.wisc.edu/SERVICE/index.php


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