Whole Health Library

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 provider, 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 has had suicidal thoughts in the past. Frank is reluctant to change medications again because he has already done so three times. Frank’s clinician, is wondering what other options to consider to help Frank and has connected Frank with some Whole Health colleagues at the local VA hospital, including a psychologist who also teaches meditation and a psychiatrist who is known to “think outside the pillbox.”

Frank has been receiving 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 (and complicated grief) 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 for the past few years. Recently, he has lost several of his friends, and he is beginning to feel the effects of aging. Frank agrees with his provider about needing to do more about his depression.

Frank’s provider suggested he take home and fill out a Personal Health Inventory (PHI) to help identify what really matters to him. He scheduled a visit with a Whole Health Coach, and was introduced to Jerry, a Whole Health Partner who has dealt with depression himself.

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

On his PHI, Frank rates himself a 2 out of 5 for his overall physical well-being and a 1 for overall mental and emotional well-being. When asked what matters most to him and why he wants to be healthy, Frank responds:

“My family is important to me. I feel great whenever I talk to my grandchildren or I’m spending time with them.”

For the eight areas of self-care, Frank rates himself on where he is, and where he would like to be. After discussing options with Jerry and his Whole Health Coach, Frank decides to first focus on the areas of Moving the Body and Recharge by walking every day and talking with his grandchildren, who live some distance away, at least 4 times a week. He also agrees to try Mindfulness-Based Cognitive Therapy (MBCT).

For more information, refer to Frank’s PHI.

One in 10 adult Americans suffers from a depressive disorder, with nearly 7% of adults experiencing major depressive disorder in any given year.[1] Depression is the most common mental illness[2] and the leading cause of disability worldwide.[3] Fourteen percent of U.S. Veterans have been diagnosed with depression, but studies indicate it is underdiagnosed in this population.[4]

Emotional health is an important aspect of mental health, not to mention an important aspect of Whole Health. Humans experience multiple emotional states (over 27, according to one recent study, though estimates vary).[5] Some argue that depression is the quintessential emotional disorder; people who suffer from it will go so far as to say that not only might it include sadness, guilt, remorse, or fear, but that it may in fact create a complete absence of emotion altogether. Depression is a complex, challenging-to-treat, and often terminal disorder, and the Whole Health approach can be of great use in helping people who have depression find healing.

Not surprisingly, depression is one of the chronic conditions for which (CIH) therapies are most frequently used.[6] The 2015 HAIG report, which surveyed 141 VA facilities, found that depression was one of the top five most common diagnoses for which Veterans are treated within VA using CIH.[7]

Personalizing Care

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 PHP that they truly identify as their own and are willing to follow. Many different aspects of lifestyle can make an important difference in the course of depression.[11]

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) include the following[12]:

• 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.[12] 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 majority of depressed patients present with somatic complaints, as opposed to reporting depressed mood.[13]

Depression does not typically occur alone; it is associated with multiple comorbidities. A study focused on data from nearly 250,000 people from 60 countries found that 9%-23% of people with at least one chronic physical disease had depression as well, and this was much higher than the risk of having depression in the absence of a chronic physical illness.[14] The authors concluded that “depressions produces the greatest decrement in health compared with the chronic diseases angina, arthritis, asthma and diabetes.” In addition to being linked to all-cause mortality, depression is significantly associated specifically with cardiovascular disease mortality[15]; this may be due in part to the fact that people with depression use tobacco and alcohol more and eat fewer fruits and vegetables.[15] Depression is also associated with a higher relative risk (1.15) of developing some form of cancer.[16]

The etiology of depression is complex. Many genes are linked to depression and bipolar disorder.[17] Cognitive and emotional processing in the brain is altered, but studies in the last 20 years have been inconsistent as far as the details.[18] Latest research findings highlight the contributory roles of brain-derived neurotrophic factor (BDNF)[19], chronic inflammation[20], and the microbiome[21], among many other influences.

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.[22] Collaborate Assessment and Management of Suicidality (CAMS) is an example of a more flexible and personalized approach that is beneficial to Veterans who are dealing with suicidal ideation.[23] This approach, built around empathy, humanism, mindful awareness, and routine co-creation of a plan, was found in a 2019 trial to reduce suicide risk in a heterogeneous population of 78 participants.

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.

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.[24] This site also offers background information on the questionnaire and describes how to score it.

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. 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.[25] Specific techniques that invoke mindful awareness are featured in the Power of the Mind section, below.

Few studies have focused specifically on using mindful-awareness training for bipolar disorder (BPD); a 2018 review found that mindful awareness may help to some degree with anxiety and depression-related symptoms, but not with manic symptoms.[26]

Exercise

Exercise has been studied extensively, and generally seems to be helpful.[27] Exercise alone offers effective treatment for mild to moderate depression when compared to medication or psychotherapy. Combining exercise with various psychotherapeutic approaches appears to be even more effective than exercise alone.[28][29] It seems to augment medication effects as well.[30]

In addition to decreasing symptoms, further benefits of exercise include reduced risk for relapse, improved self-esteem, and, of course, higher levels of physical fitness (with all the other additional health benefits that offers).[31][32] A 2013 Cochrane Review focused on exercise for depression which included 39 studies with a total of 2,326 participants concluded the following[33]:

• Exercise is “…moderately more effective than no therapy.” This effect becomes less clear when only high-quality studies are evaluated.
• It is no more effective (but also no less effective) than antidepressants or psychological therapies. This is based on a small number of studies.
• Aerobic and anaerobic activities are equally effective.[34] Total energy expenditure becomes more important than the number of times per week someone exercises.
• Exercising on an ongoing basis does make a difference. Consistency is key.[31][32]
• Physical activity may produce immediate improvement in mood.[35] Therefore, starting systematic exercise early on in a depressive episode may be especially beneficial during the period of waiting for medications or psychotherapy to take effect.

Physical activity reduces risk of suicidal ideation, according to a 2018 meta-analysis.[36] People who are active versus inactive in general have a lower risk (OR=0.87). The same was true for those who met activity guidelines versus those who did not (OR=0.91).

A 2017 study found that five different genetic patterns that were linked to an increased risk of depression and suicidal ideation were attenuated by regular exercise in military personnel.[37]

How does physical activity help? Exercise has been shown to regulate neurotransmitters and promote nerve cell growth; exactly how it affects depression is unknown.[38][39] It may be due to changes in nerve cell development in the brain.[40] Reduction in nerve cell growth and toxicity in the hippocampus are thought to be mediated through proinflammatory chemicals, such as IL-6. Increases in macrophage activity and in the production of proinflammatory cytokines have been consistently reported in depressed patients.[41] It has been shown that exercise can alter cellular immunity and reduce markers of inflammation, thereby modifying the metabolism of key neurotransmitters.[40]

• For more information, refer to “Moving the Body.”

Yoga

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 diverse traditions incorporating a wide variety of techniques. Yoga is perhaps best used adjunctively, as a way to promote good overall physical and mental health, rather than just as a specific intervention for depression.[42] A 2013 meta-analysis found that 12 randomized controlled trials (RCTs)—with some methodological limitations noted—of 619 participants concluded yoga had moderate short-term beneficial effects on severity of depression, compared to usual care.[43] It was less beneficial than aerobic exercise or relaxation.

Potential reasons for yoga to have positive effects on depression include modulation of the HPA axis, regulation of neurotransmitters, decreases in rumination, promotion of more adaptive thinking, and behavioral activation.[42]

For more information, refer to Yoga.

Tai chi

A 2014 meta-analysis involving 42 studies found that tai chi appears to have benefit, but methodological qualities of studies is low.[44] Limited evidence seems to suggest both short- and long-term tai chi practices (40-minute sessions, ranging from one to four sessions per week over a course of 6 to 48 weeks) reduce depression symptoms.[45] No adverse events related to the use of tai chi for depression treatment have been reported.

More information is available in the Whole Health overview “Moving the Body.”

Light therapy

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.[46] High serotonin receptor density is associated with low extracellular serotonin and vice versa.[47] 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.[48] As a primary treatment, Light Therapy may be recommended as a one- to two-week time-limited trial in mild to moderate seasonal depression.[49]

American Psychiatric Association guide­lines for the treatment of major depressive disorder, both seasonal and nonseasonal, con­sider bright Light Therapy a low-risk and low-cost option.[50] A few meta-analyses, including Cochrane review, supported at least modest benefit of Bright Light Therapy when compared with placebo for nonseasonal depression. [49][51] There are a few side effects associated with Light Therapy. Headache, eye strain, nausea, agitation, and potential hypomania induction in some patients with bipolar disorder may occur.[52]

Light Therapy dosing recommendations range from 30 to 60 minutes of full-spectrum (10,000 Lux) light daily from special bulbs, or indirect 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°.[53]

Positive psychology

In 1998, Seligman established positive psychology, which 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.[54]

A recent review found that positive psychology interventions led to lasting increases in happiness and decreased depressive symptoms.[55] A systematic review of 3,400 studies found that 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.[56]

Resilience Programs

A 2016 study found that prevention programs focused on parents and children with an intent to prevent substance abuse and the onset of mental health disorders also decreased long-term suicide risk.[57]

General nutrition recommendations

Numerous clinical and observational studies have focused on whether or not there is an association between type of diet and depression onset.

• A 2018 review concluded that “…the number of persons who would need to change their diet, from the lowest- to the highest-quality category in order to prevent one case of depression is approximately 47.”[58] The authors note that this is on par with the number needed to treat for many other interventions (including statin drugs to prevent vascular disease.) They also note that more research is needed to confirm how diet and depression relate to one another.
• A 2009 study including nearly 2,500 participants found that a diet high in processed foods was a risk factor for depression in the next five years, whereas a whole foods diet reduced risk.[59]
• A 2016 review concluded a reduced risk of depression was linked most strongly with increasing dietary intake of seafood, vegetables, fruits, and nuts.[60]
• 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 2010 meta-analysis noted that people with obesity are 55% more likely to develop depression, and depressed patients are more likely to become obese.[61]

A few studies support a causal relationship between daily excess sucrose and caffeine intake and depression.[62][63]. 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. Symptoms recurred when patients were challenged with these substances again but not when they were given placebo.[64]

A 2011 Spanish study found that consuming fast food and commercial baked goods may have a detrimental effect on depression as well.[65] Consuming raw fruits and vegetables also seems to lower risk of depression, though consuming them in processed forms may not.[66]

A systematic review concluded that the only nutrients favorably associated with depression risk were folate, omega-3 fatty acids, and monounsaturated fatty acids. Beneficial foods included olive oil and fish. Beneficial diets included those rich in fruits, vegetables, nuts, and legumes.[67] These associations differed between men and women, and some were nonlinear.

Eating a Mediterranean-style diet has the potential to significantly reduce depression risk.[68] Alcohol-related problems are more likely in depressed people.[69] Alcohol temporarily increases serotonin, but ultimately it decreases neurotransmitter levels.[70] Elimination of alcohol seems to reduce depressive symptoms.[11]

Anti-inflammatory diet

Data from the Nurses’ Health Study indicates that a proinflammatory diet pattern increases depression risk.[71] Several anti-inflammatory diets have been developed and may prove beneficial.[72] For further details, review the “Whole Health Tool: The Anti-Inflammatory Diet” in the Passport to Whole Health.

Probiotics

Intestinal microbial composition influences centrally mediated systems involved in mood.[73] Recent studies also suggest that the intestinal microbial balance may alter the regulation of inflammatory responses and influence mood through those means. However, a 2018 meta-analysis concluded that current evidence suggests probiotic supplementation has an overall insignificant effect on mood.[74] Few studies specifically related to depression have been conducted, and more studies are needed, particularly around specific species and time courses, as well as different types of depressive disorders. For more information, refer to “Promoting a Healthy Microbiome with Food and Probiotics.”.

Sleep

There is growing body of research indicating that sleep and depression have a powerful influence on one another. A prospective study showed reciprocal effects for major depression and sleep deprivation among adolescents.[75] A 2011 meta-analysis showed that nondepressed people with insomnia (compared to people with no sleep difficulties) have double the risk of developing depression.[76] Poor sleep is also associated with increased risk of suicidal ideation, suicide attempts, and deaths by suicide.[77][78]

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.

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.[79]

Cognitive Behavioral Therapy for Insomnia (CBT-I) led to a significantly greater remission rate in both depression and insomnia.[80] Eight weeks of Mindfulness-Based Cognitive Therapy (MBCT) targeting insomnia also improved sleep, anxiety, and depressive symptoms in patients with anxiety.[81]

For more information, refer to “Recharge.”

Social support is a key component of depression treatment.[82][83][84] Higher social support has been linked to lower risk of suicide in OEF and OIF Veterans.[85] A 2018 trial found that “loneliness was associated with higher levels of depression and suicidal ideation, as well as lower patient activation and help-seeking intentions.”[86] The converse was also true.

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.[87] Interpersonal influences have an effect on emotional regulation. How a person responds may be linked to depression risk.[88] Social support intervention should focus on both strengthening relationships that fulfill basic psychological needs and removing those the patient sees as undermining their well-being.

Spirituality 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.[89] Frequency of church attendance was not significantly related to depression risk.[89] Placing a high importance on religion or spirituality is associated with having a thicker cerebral cortex.[90] This may confer resilience to the development of depressive illness in individuals at high familial risk for major depression.

A 2019 evaluation of data from the National Health and Resilience in Veterans Study concluded that a higher level of “global meaning” reported by Veterans was linked to a significantly lower likelihood of suicide in Veterans who experienced morally injurious experiences related to deployment.[91]

For more information, refer to the “Spirit & Soul” overview.

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.[92][93] In general, mindfulness meditation affects the prefrontal cortex, reducing vulnerability to depression, and it decreases rumination and reactivity.[94] A number of mindfulness-based interventions have demonstrated effectiveness for reduction in depression symptoms, including the following[95][96]:

Mindfulness-Based Stress Reduction (MBSR)

More information about MBSR courses can be found at UMass Center for Mindfulness. In Veterans, one trial found improvements in perceived stress, depressive symptoms, and quality of life after a six-week mindfulness course.[97] Mindfulness-based stress reduction has been successfully used in the VA environment for depression and PTSD. [98] It also improved quality of life.

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.[99] It is strongly recommended as an adjunctive treatment for unipolar (nonbipolar) depression and has strong evidence supporting its use.[100]. It significantly reduces risk of remission of depressive episodes, as well as overall symptom levels.[94]

Mindfulness-Based Touch Therapy

This therapy involves the use of a passive body intervention in combination with mindfulness as an active meditative discipline. A small study found it led to 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.

Compassion Training

A recent study suggested that compassionate mind training could lead to significant reductions in depression, anxiety, self-criticism, and shame.[101] The function of a part of the brain known as the amygdala is impaired in a number of mental disorders, including depression.[102] Functional MRI studies of the effect of mindfulness on the amygdala found that after an eight-week course of cognitively-based compassion training, there was an increase in right amygdala response to negative images. This change in the amygdala was significantly correlated with a decrease in depression scores.[103]

Hypnotherapy

Hypnotherapy has been around for more than a century, and its role in treating depression has been investigated for the past 20 years.[104] A recent meta-analysis based on a small number of studies suggested that hypnotherapy is a viable nonpharmacologic intervention for addressing symptoms of depression. At this point, there is a need for more trials that tease out differences in efficacy between specific types of hypnotherapy.[105]

In the general population, hypnotherapy appears to have minimal adverse effects. Its success depends largely on the engagement of the patient. Therapists must have skill in determining who is or is not an appropriate hypnotherapy candidate, as some people with past traumatic experiences may have them activated through entering a trance state. One study 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.[106]

Cognitive hypnotherapy (CH). Alladin and collaborators combined hypnotherapy and CBT to create cognitive hypnotherapy, which became the focus of an evidence-based handbook they developed.[107] CH is thought to achieve benefits through six means: 1) altering depressive mood, 2) establishing positive expectancy, 3) countering depressive rumination, 4) developing antidepressive neuropathways, 5) accessing and restricting unconscious cognitive distortions, and 6) behavioral activation.

Guided Imagery

Research related to Guided Imagery for depression is limited. It is known that people with depression have more intrusive imagery and less ability to generate positive imagery, but more research is needed regarding how treatment can use imagery to help with depression.

Relaxation

A 2008 Cochrane review concluded that in general, “Relaxation techniques were more effective at reducing self-rated depressive symptoms than no or minimal treatment, but not as effective as psychological treatment.”[108]

Psychotherapy

Psychotherapy takes many forms, some of which are more widely used in health care settings than others. Various types of psychotherapy are featured in the next section 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 therapies invoke the “Power of the Mind” in various ways.

Music Therapy

A 2017 Cochrane review concluded that Music Therapy (MT) has short-term benefits for depression and works better when combined with medications than when medications are given alone.[109] Several trials have been published recently, mostly in older patients, which suggest potential antidepressive effects when Music Therapy was added to usual care. A dose effect was seen: Benefits were more pronounced with longer durations of treatment.[110] A Cochrane Review on MT for depression found only five trials that met inclusion criteria.[111] It concluded MT is well tolerated by people with depression and appears to be associated mostly with improvements in mood. Risks are minimal.

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. A 2018 Cochrane review concluded, “Moderate-quality evidence shows that psychotherapy added to usual care (with antidepressants) is beneficial for depressive symptoms and for response and remission rates over the short term for patients with treatment-resistant depression. Medium- and long-term effects seem similarly beneficial….”[112]

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.

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.

Cognitive Behavioral Therapy (CBT)

CBT is the most-studied psychotherapy used for depression.[113] The clinician guides the patient in identifying and replacing negative patterns of thinking with more positive and realistic approaches. CBT includes education about the relationship between thoughts, behaviors, and emotions. Patients are taught behaviors that serve as more productive responses to challenging circumstances or feelings. CBT is considered a short-term therapy; the length is usually 10-20 sessions. For more information, refer to the National Alliance on Mental Illness (NAMI) website.

CBT decreases the risk of relapse if continued when a person is doing well. [114] CBT can be as effective as medications in the acute treatment of depressed outpatients.[115]

Interpersonal Therapy (IPT)

Developed in the 1970s, IPT is based on the idea that many psychological symptoms arise through interpersonal distress. Treatment usually is offered for 12-16 weeks and focuses on exploring relationships and how they influence—and are influenced by—one’s behavior and mood.

IPT’s efficacy has been shown in RCTs.[116][117] IPT can be as effective as medications in the acute treatment of depressed outpatients.[115] 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.[118]

For more information, refer to the International Society for Interpersonal Psychotherapy website.

Psychodynamic Therapy (PT)

PT is defined differently in various studies. It is also known as insight-oriented therapy. It focuses on gaining insight into unconscious processes and how they manifest in the way a person behaves.[119] Recent meta-analyses suggest that both short-term and long-term psychodynamic psychotherapy are effective for depressed patients.[120][121]

For more information, go to the Good Therapy website.

Problem-Solving Therapy (PST)

PST is a brief intervention, done in four to eight sessions. A therapist reviews the problems a person is experiencing in his or her life and then focuses on solving one or more of those problems to demonstrate more effective problem-solving techniques. PST has shown modest improvement in study participants with mild depressive symptoms; most studies have been done with geriatric populations. Twelve sessions of problem-solving therapy were superior to supportive psychotherapy for this population with major depressive disorder and executive dysfunction.[122]

For more information, refer to the University of Auckland Problem Solving Therapy website.

Marital Therapy (MT)

MT, or couple’s therapy, involves working with both the depressed individual and their significant other. MT showed comparable efficacy to individual psychotherapy for the treatment of depression in a 2006 meta-analysis.[123] Several reviews have found that MT therapy is effective for treating depressive symptoms and reducing risk for relapse.[124][125] Some individual studies have suggested that the efficacy of MT may depend on whether or not marital problems are present.[126] Lower dropout rate and greater improvement in subjective symptoms of depression, at no greater cost, were found for a couples therapy group in comparison to medications alone.[127]

Patients with major depressive disorder admitted to inpatient units were more likely to improve if family therapy was part of their treatment. They had significant reductions in interviewer-rated depression and suicidal ideation.[128]

Acceptance and Commitment Therapy (ACT)

This is another approach that incorporates mindful awareness to prevent depression relapse. It is classed in this document as a “conventional therapy” because it is rapidly gaining popularity in VA facilities. Research has shown that ACT has powerful positive effects on depression, as well as many other illnesses.[129] ACT invokes mindfulness techniques, acceptance, and commitment/behavior-change strategies to enhance a person’s psychological flexibility. A person learns to focus 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, refer to the Association for Contextual Behavioral Science (ACBS) website.

PHARMACEUTICALS

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.[130] 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.[22] Specific guidance for pharmacotherapy for depression is beyond the scope of this document, but numerous large-scale reviews can be helpful.[130]

One recent study of note found that pharmaceutical treatments prevent the progression of microglial (nervous system immune cell) activation that otherwise will progress in people with depression.[131] SSRIs seem to induce a “juvenile-like neuroplasticity” in the adult brain.[132]

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.[133] ECT should be contemplated in patients who fail to respond to medication and/or psychotherapy interventions.[134] 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.[135]

Transcranial magnetic stimulation (TMS)

TMS aims to produce electrical stimulation of superficial cortical neurons at left dorsolateral prefrontal cortex through the use of a magnetic coil that generates rapidly alternating magnetic fields. These fields are similar in strength to those used for MRIs.[136] TMS has been approved by the FDA to treat depression in patients who have not had an acceptable response to at least one antidepressant trial in the current episode of illness. Most, but not all, meta-analyses have found small to moderate benefits of TMS in depression. Efficacy is either less than or similar to that of ECT.[137] TMS is well tolerated; the most common side effects are transient scalp discomfort and headaches.[138]

Vagus nerve stimulation (VNS)

VNS involves implanting a device that sends electrical pulses to the brain. It has been found useful in chronic depression, but not in the acute phase.[139] In 2005, based on clinical trial data, the FDA approved the use of VNS as an adjunctive therapy for treatment-resistant depression in adult patients who have failed four or more medications. VNS can safely be combined with ECT for patients with acute relapse. The cost is very high, around above $40,000 for a day of surgery plus adjustments.[140]

A 2015 review noted that 10%-30% of people with depression and 20%-50% of those with bipolar disorder used CIH.[141] It is important to ask patients about use, and it is important, regardless of your standpoint regarding the use of complementary approaches, to be able to discuss them with people in your care. In 2016, the Canadian Network for Mood and Anxiety Therapies (CANMAT) created guidelines regarding CIH for depression, noting, ”For major depressive disorder (MDD) of mild to moderate severity, exercise, Light Therapy, St. John’s wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John’s wort are second-line recommendations for moderate to severe MDD.[142]

Nonbotanical supplements

Omega-3s, 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.

Folate

People with depression have lower folate levels and lower dietary intake of folate than the general population.[144] Known to be linked to serotonin metabolism,[145] mostly due to its role in methylation reactions that form the rate-limiting step in the production of neurotransmitters like serotonin.[146] Trials identified in a 2004 Cochrane review did not find evidence of adverse effects for folate. It is not clear from the few trials that exist whether or not folate is beneficial as a treatment for depression.[147]

Inositol

Sometimes referred to as vitamin B8 (though not actually a vitamin in the strict sense), inositol is a sugar found especially commonly in the brain. It is involved in multiple cell signaling mechanisms. A meta-analysis identified two depression studies where inositol had marginally more responders in depression than placebo (p = 0.06).[147], but recent meta-analyses have not found benefit.[148] Inositol caused minimal gastrointestinal upset compared with placebo (p = 0.06)[147]} Other side effects are rare.

Magnesium

Magnesium’s first use dates back 100 years ago, when magnesium sulfate injected hypodermically was found to be helpful in patients with agitated depression.[149] A 2018 meta-analysis did not find a link between serum magnesium levels and depression.[150] Magnesium’s mechanism of action is unknown, but it may be related to the glutamatergic mechanism, since magnesium acts as physiological NMDA receptor antagonist.[151] A 2018 review notes that research remains inconclusive in terms of magnesium’s efficacy.[152] Oral magnesium supplementation may prevent depression and might be used as an adjunctive therapy, but further research is needed.[153]

Omega-3 fatty acids

People with depression have been found to have a deficiency of omega-3 fatty acids or an imbalance in the ratio of omega-6 and omega-3 fatty acids.[154] Synaptic membrane fluidity is significantly determined by cholesterol and dietary polyunsaturated fat levels, and other physiological functions are heavily reliant on them as well.[155] Therefore, optimal proportion of these elements is postulated to have an impact in depression.[156] US (APA) and Canadian guidelines support use of omega-3s for depression, noting that while efficacy may seem modest in research to date, harms are minimal.[142][157]

A 2017 network meta-analysis found that omega-3 therapy was not as effective as SSRI therapy, but that when the two were combined, the effect was better than either intervention alone.[158] A 2015 Cochrane review concluded, “At present, we do not have sufficient high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the quality of the evidence on which this result is based to be low/very low.”[159]

Two other meta-analysis concluded that omega-3 supplementation demonstrated significant clinical benefit, noting that eicosopentaenoic acid (EPA) content was particularly important.[160][161] In rat models, diets rich in omega-3 led to increased hippocampal neurogenesis.[156] An elevated ratio of omega-6 to omega-3 fatty acids predicted depression development following interferon-alpha treatment.[162] A low omega-3 index in late pregnancy was associated with a higher depression score three months postpartum.[163]

Probiotics

Taking probiotics daily may modulate immune function and mood. For mood benefits, Bifidobacterium infantis has been found especially useful.[73][164] One billion colony forming units (CFUs) is a good starting point, and taking a variety of different species may be best. It is recommended that probiotics be taken for at least two weeks and up to two months.

For more information, refer to “Promoting a Healthy Microbiome with Food and Probiotics.”

S-Adenosyl methionine (SAMe)

Pronounced “Sammy,” S-adenosyl methionine is an amino acid derivative that is found in virtually all body tissues and fluids. It plays a role in over 100 biochemical reactions, most of which involve the transfer of methyl groups. SAMe is important for the synthesis and metabolism of proteins, nucleic acids, neurotransmitters, hormones, and many other compounds. Severely depressed patients often have low levels of SAMe in the spinal fluid, and SAMe supplementation can normalize them.[165] Deficiencies of B12 and folate are linked to low levels of SAMe in the nervous system. SAMe’s mechanism of action is unclear, but higher SAMe levels have been linked to increased serotonin turnover and elevated dopamine and norepinephrine levels. SAMe is often used for treatment of both depression and pain. Some people refer to it as the supplement equivalent of duloxetine (Cymbalta). A 2016 Cochrane review that included eight trials noted a paucity of high-quality evidence but noted that SAMe often shows similar effects to SSRIs.[166] Other reviews note that it “holds promise.”

SAMe is thought to have a more rapid onset than many antidepressants, so some clinicians may use it as a stopgap while waiting for drug therapies to take effect.[167] It can significantly improve remission rates in depressed patients who do not respond to medications.[168] SAMe tends to be quite safe.[168] Side effects can occur with high doses, such as nausea, vomiting, diarrhea, constipation, nervousness, dry mouth, and headache, but these tend to be minimal in comparison with side effects from antidepressants. Mania and hypomania are rarely reported. Dosing ranges from 400 mg to 1,600 mg daily divided into two doses. SAMe’s biggest drawback is that it can be quite expensive to purchase over the counter.

Tryptophan and 5-hydroxytryptophan (5-HTP)

A Cochrane review found that in two of 108 trials, tryptophan and 5-HTP were better than placebo at alleviating depression.[167] There is a possible association between these substances and the potentially fatal eosinophilia-myalgia syndrome.[169] Most authorities agree this was largely attributable to contamination of a specific batch of supplements made by one company.Tryptophan intake in the diet is inversely associated with depression risk.[170] Most Americans get more than enough in their diets.

Zinc and other minerals

Research suggests potential benefits of zinc supplementation for depression, either as a stand-alone therapy or as an adjunct to drug therapy. A 2018 review suggested that levels of zinc, iron, copper, and selenium intake are inversely related to depression risk.[171] Zinc-sensing cell receptors may be partly linked to zinc’s efficacy.[172]

Botanicals [173]

Roughly 10 years ago, there was a 50% increase in the number of studies of botanicals for depression,[174] including a number of epigenetic studies.[175] Surveys indicate that 44%-54% of depressed patients have used herbal remedies in the past 12 months.[176] 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. Using multiple plant-based compounds (either from one remedy or a combination) may have similar benefits. A 2018 review featuring 110 herbal remedies found that only 1%-2% of studies were clinical. Most herbals, like antidepressants, affected monoamine neurotransmitters (i.e. serotonin, norepinephrine, dopamine).[177]

Ginkgo (Ginkgo biloba)

Ginkgo is useful in treating older patients (ages 51-78) with depression related to organic brain dysfunction, especially when they have proved unresponsive to standard drug treatment.[178] Dosing used in depression studies was 40 mg to 80 mg three times daily of a 50:1 extract standardized to contain 24% ginkgo-flavone glycosides. Due to potential anticoagulation effects, ginkgo should not be used by anyone during the periods before or after surgery or labor and delivery, and it should be used with caution in people with bleeding problems. It may interact with blood thinners, calcium channel blockers, aminoglycoside antibiotics, anticonvulsants, and neuroleptics.

Roseroot (Rhodiola rosea)

Roseroot significantly improved HAMD scores as well as insomnia, somatization, and emotional instability subscale outcome measures at doses of 340 mg daily of standardized extracts.[179] A review of two RCTs and multiple open-label studies found a possible anti-depressant effect.[180]

Saffron (Crocus sativus)

A 2018 review concluded that saffron has similar anti-depressant effects to SSRIs but with fewer side effects.[181] Saffron demonstrated significant improvement for depression over placebo on Hamilton Depression Rating (HAMD)scores.[182] Equivalent therapeutic response was demonstrated for saffron, imipramine 100 mg daily, and fluoxetine at 20 mg bid on the HAMD. Petals and stamens are used in doses of 30 mg daily.

St. John’s wort (Hypericum perforatum)

St. John’s wort is one of the main supplements used for treating depression. It is typically dosed at 300 mg three times a day standardized to between 3% and 6% hyperforin and not less than 6% flavonoids for depression. Outcomes in studies include reduction in Hamilton Rating Scale for Depression (HAMD) scores,[176] lower relapse rate (18%), and longer time to relapse compared to placebo groups after 26 weeks of treatment.[183] A 2017 network meta-analysis found that St. John’s wort was similar to SSRIs in terms of response rates, remission rates, and degree of change on the HAM-D scale.[158] It was found to have superior effects relative to exercise or omega-3s. Of note, it also had fewer adverse effects than SSRIs (relative risk 1.19). Another 2017 meta-analysis concluded that St. John’s wort was comparable with SSRIs for people with mild to moderate depression.[184] St. John’s wort is not just an herbal SSRI; it seems to affect multiple different biochemical pathways.

If anyone ever asks what botanical has the most interactions with medications, it is St. John’s wort. It alters the cytochrome P-450 3A4 detoxification pathway. Caution should be used with taking St. John’s wort with antiretrovirals, warfarin, cyclosporine, or oral contraceptives, among other medications. Because it is known to be a mild MAO-I, similar dietary and medication interaction precautions should be taken as with an MAO-I drug.

Turmeric (Curcuma longa)

Turmeric, a spice that is commonly used in many Asian foods, contains curcumin and other anti-inflammatories that seem to have multiple benefits for inflammation. A 2017 meta-analysis conclude that “Curcumin appears to be safe, well-tolerated, and efficacious among depressed patients.” More robust randomized controlled trials with larger sample sizes and follow-up studies carried out over a longer duration should be planned to ascertain its benefits.”[185]

NONCONVENTION BOTANICALS

Chinese Herbal Medicine (CHM)

A systematic review looking at studies that used a variety of different Chinese formulations for depression concluded that CHM was superior to placebo and as effective as antidepressants in terms of effects on HAMD scores; there were fewer adverse events as well.[186]

Psychedelics

The potential of psychedelics to treat depression and other mental health disorders is the subject of a great deal of current research. They seem to affect inflammation, and it is theorized they may also reset a number of brain networks by destabilizing and “resetting” them.[187]

Aromatherapy

Aromatherapy effected mood in several small studies. A small nonrandomized pilot trial found that adjunctive aromatherapy allowed for reductions in dose of antidepres­sants compared with usual therapy. [189] Short-term, but not persistent, mood bene­fits were found for aromatherapy with citrus oil combined with massage in patients with cancer who were suffering from depression.[190] It was not clear in the latter study how much each element, that is massage or oils, contributed to the positive effect.

BODY-BASED THERAPIES: Massage

Massage therapy, defined as 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.[191] 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 (EEG) patterns. A symmetrical or left frontal pattern is found, which is associated with positive affect. Massage also stimulates facial expressions and increases vagal activity, which has been shown to reduce depressed affect.[192] A multicenter RCT found aromatherapy massage to be associated with clinically important benefit for depression symptoms for up to two weeks in patients with cancer.[190]

A recent meta-analysis including 17 studies containing 786 persons concluded that massage therapy is significantly associated with alleviation of depressive symptoms.[193] Given this information, massage should be seen as an effective ancillary treatment that likely promotes remission maintenance.. There is no evidence to support its being used alone as a first-line therapy.

For more general information, refer to the Massage Therapy Whole Health Tool featured in the Passport to Whole Health, Chapter 16.”

Chinese Medicine and Acupuncture

In Chinese medicine (CM), one of the proposed etiologies of mental disorders is internal damage caused by the deregulation of the seven emotions: anger, worry, contemplation (thinking), sorrow (grief), fear, and shock.[194]

In acupuncture, points are stimulated by needles, electricity-augmented needles, and lasers. There are also needleless approaches. Many mechanisms of action have been proposed for acupuncture, and 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.[195]

Conclusions of various reviews of acupuncture trials are mixed, but favorable overall. A 2018 Cochrane review concluded that “Acupuncture may result in a moderate reduction in the severity of depression when compared with treatment as usual or no treatment. Use of acupuncture may lead to a small reduction in the severity of depression when compared with control acupuncture. Effects of acupuncture versus medication and psychological therapy are uncertain, owing to the very low quality of evidence.”[196] A 2013 trial found that acupuncture in combination with the drug paroxetine led to a higher treatment response rate but no changes in remission rate.[197] 2010 Cochrane review found insufficient evidence to recommend using acupuncture for depression, based on 30 studies identified as meeting inclusion criteria (n=2,812).[198] It was noted that a subgroup of 94 participants in three studies who had depression as a comorbidity did have a reduction of depression[198] 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.[199] A meta-analysis of eight RCTs by Wang and colleagues concluded that acupuncture can significantly reduce the severity of depression.[200] 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.[201] 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.[202]

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.[203] 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.[194]

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

1. The particular challenge of inadequate placebo interventions
2. Variation in definitions/diagnostic criteria of depression; most studies have been done with diagnostic criteria that differ from DSM-IV TR/V
3. Considerable disparities in the way that acupuncture is routinely practiced, especially in the West
4. Most of the evidence available is published in Chinese-language journals

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.[204] 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.

Based on the research summarized above, a Personalized Health Plan (PHP) 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.

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 pm 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.

Patient Education Programs

• Behavioral Health Lab
• Translating Initiatives for Depression into Effective Solutions (TIDES)
• VISN 2 Center for Integrated Healthcare
• University of Massachusetts Center for Integrated Primary Care
• VA-DoD Guidelines for the Management of Major Depressive Disorder (2016)
• VA Primary Care-Mental Health Integration Initiative

Also, refer to VA national rollouts for Interpersonal Psychotherapy (IPT), CBT for Depression, and Problem Solving Therapy (PST).

“Depression” was written by Mario Salguero, MD, PhD, and updated by J. Adam Rindfleisch, MPhil, MD (2014, 2019).