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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 Clinical Tool

WHOLE HEALTH: CHANGE THE CONVERSATION Depression

Clinical Tool

This clinical tool summarizes key points from the Depression educational overview. See the overview for additional details. Introduction 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 Defining Depression A person may have a depressive disorder if he or she has several of the following symptoms, they last more than two weeks, and they negatively affect level of functioning, especially daily activities. Symptoms may vary in presence and severity over time, and different people may experience a different combination of them. They include

• Sad or irritable mood • Major changes in sleep, appetite, and energy • Difficulty thinking, concentrating, and remembering • Physical slowing or restlessness • Lack of interest in or pleasure from activities that were once enjoyed • Feelings of guilt, worthlessness, hopelessness, and emptiness • Recurrent thoughts of death or suicide • Physical symptoms that do not respond to treatment, such as headaches,

digestive disorders, and pain. 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.5 Grief and depression are not the same. See the Grief module for more information.

VHA Office of Patient Centered Care and Cultural Transformation Page 1 of 27

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

WHOLE HEALTH: CHANGE THE CONVERSATION Clinical Tool: Depression

Personalizing Care There are many different “types” of depressive disorders, and it can help to know treatment can be guided by a knowledge of which type a given person has. Like any other illness, there are different types of depression, classified mostly by the presentation at the clinic, based on duration, timing, or presumed etiology.6 For example, a person may have a depressive disorder due to another medical condition or due to substance use or medications, or a woman may have premenstrual dysphoric disorder. If a patient has bipolar disease, depression may be just one half of the overall picture. First things first: Be aware of suicide risk for each individual Individualizing care starts with gauging the risk depression poses to a person. Suicide must always be kept in mind when you see a patient with depression or other conditions that predispose to higher suicide risk, such as posttraumatic stress disorder (PTSD), sleep disorders, substance use problems, and chronic pain.

Know your patient

• 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 better results than a less-empathic clinician with medications.7

• Treatment is most effective when tailored to the individual. The Personal Health Plan will be influenced by disease severity and patient preferences, as well as based on the particular interventions accessible to a given patient.

Mindful Awareness and Depression Mindful awareness has been described as the practice of learning to focus attention on moment-by-moment experience with an attitude of curiosity, openness, and acceptance. (For details, see the Mindful Awareness module.) Mindful awareness is a general approach to living, but it can be used to work with many specific issues or concerns, such as depression. A particularly helpful resource is the book The Mindful Way Through Depression, by Mark Williams and colleagues.8 For more

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 Basics http://www.mentalhealth.va.gov/communityproviders/clinic_suicideprevention.asp - sthash.EV6SsvnS.dpbs.


http://veteranscrisisline.net/



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

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


details, see the information on “Mindfulness-Based Therapies” under “Power of Mind,” below. Working Your Body Exercise

• Exercise has been studied extensively, and generally seems to be helpful.9 • Combining exercise with various psychotherapeutic approaches appears to

be even more effective than exercise alone.10,11 • 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.12,13

• A recent Cochrane Review focused on exercise for depression which included 39 studies with a total of 2,326 participants concluded the following:14

o Exercise is “…moderately more effective than no therapy.” This effect becomes less clear when only high-quality studies are evaluated.

o It is no more effective (but also no less effective) than antidepressants or psychological therapies. This is based on a small number of studies.

o Aerobic and non-aerobic activities are equally effective.15 Total energy expenditure becomes more important than the number of times per week someone exercises.

o Exercising on an ongoing basis does make a difference. Consistency is key.

o Physical activity may produce immediate improvement in mood.16 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.

• See the Working Your Body module for more information. Yoga

• Yoga should perhaps best be seen more as a way to promote good overall physical and mental health, rather than as a specific intervention for depression.17

• A recent 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.18 It was less beneficial than aerobic exercise or relaxation.

• For more information see the Yoga: Looking Beyond “The Mat” clinical tool. Tai chi

• A recent meta-analysis found evidence 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.19 No



adverse events related to the use of tai chi for depression treatment have been reported.

Surroundings Light therapy

• Light therapy has been commonly used for patients with seasonal affective disorder, and it has been found useful as an adjunctive modality with pharmacotherapy in both unipolar and bipolar depression.20 As a primary treatment, light therapy may be recommended as a one to two week time-limited trial in mild to moderate seasonal depression.21

• A few meta-analyses, including Cochrane review, supported at least modest benefit of bright light therapy when compared with placebo for non-seasonal depression. 21,22

• 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.23

• 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.

o One should not stare directly at a light source. o Therapy is effective so long as light is able to meet the eye at an angle

of 30–60°.24 Aromatherapy Aromatherapy has been shown to have an effect on mood in several small studies. A small non-randomized pilot trial found that adjunctive aromatherapy allowed for reductions in dose of antidepressants compared with usual therapy. 25 Music therapy

• 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.26

• The latest Cochrane Review on music therapy for depression found only five trials that met inclusion criteria.27 It concluded that music therapy is well tolerated by people with depression and appears to be associated mostly with improvements in mood. Risks are minimal.

Personal Development Positive psychology

• A recent review found that positive psychology interventions led to lasting increases in happiness and decreased depressive symptoms.28 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.29

• 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.29-31

• A few studies support a causal relationship between daily excess sucrose and caffeine intake and depression.32,33

• 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.34

• 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.35 These associations differed between men and women, and some were nonlinear.

• Eating a Mediterranean-style diet has the potential to significantly reduce depression risk.36

Anti-inflammatory diet Data from the Nurses’ Health Study indicates that a pro-inflammatory diet pattern increases depression risk.37 Several anti-inflammatory diets have been developed and may prove to be beneficial.38 For further details, see The Anti-Inflammatory Diet clinical tool. Probiotics Intestinal microbial composition influences centrally-mediated systems involved in mood.39 Recent studies also suggest that the intestinal microbial balance may alter the regulation of inflammatory responses and influence mood through those means. See the Promoting a Healthy Microbiome with Food and Probiotics clinical tool for more information. Recharge Sleep 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.40

• 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.41

• Cognitive behavioral therapy (CBT) targeting insomnia led to a significantly greater remission rate in both depression and insomnia.42

• Eight weeks of mindfulness-based cognitive therapy targeting insomnia also improved sleep, anxiety, and depressive symptoms in patients with anxiety.43

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.44-46 • 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.47

• Social support intervention should focus on both strengthening relationships that fulfill basic psychological needs and removal of those the patient sees as undermining their well-being.

Spirit and Soul

• Spirituality can play a significant role in influencing mood. • 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.48

• Frequency of church attendance was not significantly related to depression risk.48

• For more information, see the Spirit and Soul module. Power of the Mind49,50 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 the following:51,52



• Mindfulness-based stress reduction (MBSR) 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.53 Mindfulness-based stress reduction has been successfully used in the VA environment to show benefit in treating depression and PTSD while improving quality of life.54

• Mindfulness-based cognitive therapy (MBCT) MBCT adapts the principles of the MBSR eight-week training course specifically to patients with bouts of recurrent depression.55 It is strongly recommended as an adjunctive treatment for unipolar (non-bipolar) depression and has strong evidence supporting its use.56

• 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.57

• Compassion training A recent study suggested that compassionate mind training could lead to significant reductions in depression, anxiety, self-criticism, and shame.58 The function of a part of the brain known as the amygdala is impaired in a number of disorders, including depression.59 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.60

Hypnotherapy Hypnotherapy has been around for more than a century, and its role in treating depression has been investigated for the past 20 years.61 A recent meta-analysis based 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 specific types of hypnotherapy.62 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 with specific credentialing. 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. Dobbin found self-hypnosis to be a


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


preferred mode of treatment of depression in a primary care setting and comparable to medications and CBT, in a partially randomized preference study design.63

• 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.64 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.

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.”65 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. Conventional Approaches to Depression Psychotherapy-based approaches

• Clinical evidence supports the use of several psychotherapy modalities for depression. These approaches have minimal side effects and long-lasting benefits. The modalities that have been studied most and found to be most effective include

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

• Others with growing research and evidence to support their use include o Hypnotherapy o Cognitive hypnotherapy o Mindfulness-based cognitive therapy (featured in the Power of Mind

Section, above) o Acceptance and commitment therapy o 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. Using it in combination with medications appears to have superior efficacy compared 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 the following link: http://www.apa.org/helpcenter/psychotherapy-works.aspx.

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)

In CBT, the clinician guides the patient in identifying and replacing negative patterns of thinking with more positive and realistic approaches.

o 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.

o CBT is considered a short-term therapy; the length is usually 10 - 20 sessions.

o For more information, see the National Alliance on Mental Illness (NAMI) website at the following link: http://www.nami.org/Content/NavigationMenu/Inform_Yourself/About_Mental_Illness/About_Treatments_and_Supports/Cognitive_Behavioral_Therapy1.htm.

o CBT decreases the risk of relapse even after formal treatment sessions are completed.66 CBT can be as effective as medications in the acute treatment of depressed outpatients.67

• Interpersonal therapy (IPT)

o Developed in the 1970s, IPT is based on the idea that many psychological symptoms arise through interpersonal distress.

o 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.

o IPT’s efficacy has been shown in RCTs.68,69 IPT can be as effective as medications in the acute treatment of depressed outpatients.67

o 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.70

o For more information, see the website for the International Society for Interpersonal Psychotherapy at http://interpersonalpsychotherapy.org/about-ipt/.


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://interpersonalpsychotherapy.org/about-ipt/


• Psychodynamic therapy (PT) o PT is defined differently in various studies. o PT is also known as insight-oriented therapy. o It focuses on gaining insight into unconscious processes and how they

manifest in the way a person behaves.71 o Recent meta-analyses suggest that both short-term and long-term

psychodynamic psychotherapy are effective for depressed patients.72,73 For more information, see the GoodTherapy.org Website at http://www.goodtherapy.org/psychodynamic.html.

• Problem-solving therapy (PST)

o PST is a brief intervention, done in four to eight sessions. o 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.

o PST has shown modest improvement in study participants with mild depressive symptoms; most studies have been done with geriatric populations.

o Twelve sessions of problem-solving therapy were superior to supportive psychotherapy for this population with major depressive disorder and executive dysfunction.74

o For more information, see the University of Auckland PST website at http://www.problemsolvingtherapy.ac.nz/index.php?p=steps.

• Marital therapy (MT)

o Marital therapy, or couples therapy, involves working with both depressed individuals and their significant others.

o MT showed comparable efficacy to individual psychotherapy for the treatment of depression in a 2006 meta-analysis.75

o Several reviews have found that marital therapy is effective for treating depressive symptoms and reducing risk for relapse.76,77

o Some individual studies have suggested that the efficacy of marital therapy may depend on whether or not marital problems are present.78

o 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.79

o 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.80


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

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


• Acceptance and commitment therapy (ACT) o This approach also 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.

o Research has shown that ACT has powerful positive effects on depression, as well as many other illnesses.81

o 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.

o To learn more, see the website link 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.82

• Effectiveness of antidepressant medications is generally comparable between classes and within classes of medications.

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.

Other conventional approaches

• Electroconvulsive therapy (ECT) o 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.83

o ECT should be contemplated in patients who fail to respond to medication and/or psychotherapy interventions.84

o 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.85

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


http://contextualscience.org/act

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

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

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


• Transcranial magnetic stimulation (TMS) o 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 MRI’s.86

o 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.

o 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.87

o TMS is well tolerated; the most common side effects are transient scalp discomfort and headaches.88

• Vagus nerve stimulation (VNS)

o 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.89

o 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.

o VNS can safely be combined with ECT for patients with acute relapse. o The cost is very high, around above $40,000 for a day of surgery plus

adjustments.90 Complementary Approaches to Depression Acupuncture

• In traditional Chinese medicine (TCM), 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.91

• In acupuncture, points are stimulated by needles, electricity-augmented needles, and lasers. For more information, see the clinical tool, Acupuncture and Traditional Chinese Medicine. 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.92

• Conclusions of various reviews of acupuncture trials are mixed, but favorable overall.

o 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).93 It was noted that a subgroup



of 94 participants in three studies who had depression as a comorbidity did have a reduction of depression93 in comparison with the use of SSRIs.

o 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.94

o A meta-analysis of eight RCTs by Wang and colleagues concluded that acupuncture can significantly reduce the severity of depression.95

o 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.96

o 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.97

o 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.98 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.91 • 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.99 See the Homeopathy clinical tool for more information.

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.100

• 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.101

• 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.102

• A recent meta-analysis including 17 studies containing 786 persons concluded that massage therapy is significantly associated with alleviation of depressive symptoms.103

• 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 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. What follows is summary of some of the key research regarding various dietary supplements for the treatment of depressive disorders. Please note that this covers the most-studied and most-used supplements in the U.S., but there are many more that your patients might be taking as well. Non-botanical supplements 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.



• Folate o Known to be linked to serotonin metabolism,104 mostly due to its role

in methylation reactions that form the rate-limiting step in the production neurotransmitters like serotonin.105

o Trials identified in a 2004 Cochrane review did not find evidence of adverse effects for folate.

o Limited evidence suggests folate may have a potential role as an adjunct to other treatments for depression.106

• Inositol o A meta-analysis identified two depression studies where inositol had

marginally more responders in depression than placebo (p = 0.06).106 o Inositol also marginally caused gastrointestinal upset compared with

placebo (p = 0.06).106 o May have limited benefit for depression.107

• Magnesium o Magnesium’s first use dates back 100 years ago, when magnesium

sulfate injected hypodermically was found to be helpful in patients with agitated depression.108

o Magnesium’s mechanism of action is unknown, but it may be related to the glutamatergic mechanism, since magnesium acts as physiological NMDA receptor antagonist.109

o A 2013 systematic review suggests that magnesium may be effective in the treatment of depression, but evidence is limited overall.109

o Oral magnesium supplementation may prevent depression and might be used as an adjunctive therapy, but further research is needed.110

• Omega-3 fatty acids

o 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.111 Synaptic membrane fluidity is significantly determined by cholesterol and dietary polyunsaturated fat levels. Therefore, optimal proportion of these elements is postulated to have an impact in depression.112

o A clinically relevant antidepressant effect was demonstrated recently in a post hoc analysis of depressed patients who supplemented their diets with omega-3 fatty acids (DHA/EPA) in addition to taking their conventional antidepressants.113

o Interestingly, in rat models, diets rich in omega-3 led to increased hippocampal neurogenesis.112

o An elevated ratio of omega-6 to omega-3 fatty acids predicted depression development following interferon-alpha treatment.114



o A low omega-3 index in late pregnancy was associated with a higher depression score three months postpartum.115

• Probiotics o Taking probiotics daily may modulate immune function and mood.

For mood benefits, Bifidobacterium infantis has been found especially useful.39,116

o One billion colony forming units (CFUs) is a good starting point, and taking a variety of different species may be best.

o It is recommended that probiotics be taken for at least two weeks and up to two months.

o See the Promoting a Healthy Microbiome with Food and Probiotics clinical tool for more information.

• S-Adenosyl methionine (SAMe)

o 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.

o SAMe is important for the synthesis and metabolism of proteins, nucleic acids, neurotransmitters, hormones, and many other compounds.

o Deficiencies of B12 and folate are linked to low levels of SAMe in the nervous system.

o SAMe’s mechanism of action is unknown, but higher SAMe levels have been linked to increased serotonin turnover and elevated dopamine and norepinephrine levels.

o Severely depressed patients often have low levels of SAMe in the spinal fluid, and SAMe supplementation can normalize them.117

o SAMe is often used for treatment of both depression and pain. Some people refer to it as the supplement equivalent of duloxetine (Cymbalta).

o SAMe significantly improves symptoms of depression.118 o SAMe tends 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.119

o It can significantly improve remission rates in depressed patients who do not respond to medications.118

o SAMe tends to be quite safe.118 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.

o 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.



• Tryptophan and 5-hydroxytryptophan (5-HTP) o A Cochrane review found that in 2 out of 108 trials, tryptophan and 5-

HTP were better than placebo at alleviating depression.119 o There is a possible association between these substances and the

potentially fatal eosinophilia-myalgia syndrome.120 Most authorities agree this was largely attributable to contamination of a specific batch of supplements made by one company.

• Zinc o Research suggests potential benefits of zinc supplementation for

depression, either as a stand-alone therapy or as an adjunct to drug therapy. However, a recent systematic review of RCTs found methodological limitations in existing studies and recommended further research.121

Botanicals

• Recently, there has been a 50% increase in the number of studies of botanicals for depression,122 including a number of epigenetic studies.123

• Surveys indicate that 44-54% of depressed patients have used herbal remedies in the past 12 months.124

• 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.

o 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.

o 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)

o St. John’s wort is typically dosed at 300 milligrams three times a day standardized to between 3% and 6% hyperforin and not less than 6% flavonoids for depression.

o Outcomes in studies include reduction in Hamilton Rating Scale for Depression (HAMD) scores,124 lower relapse rate (18%), and longer time to relapse compared to placebo groups after 26 weeks of treatment.125

o Three studies showed an effect of St. John’s wort that was comparable to pharmaceuticals.126



o 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 a MAO-I drug.

o St. John’s wort is not just an herbal SSRI; it seems to affect multiple different biochemical pathways.

• Roseroot (Rhodiola rosea) o Roseroot significantly improved HAMD scores as well as insomnia,

somatization, and emotional instability subscale outcome measures at doses of 340 milligrams daily of standardized extracts.127

• Saffron (Crocus sativus) o Saffron demonstrated significant improvement for depression over

placebo on HAMD.128 o Petals and stamens were used in doses of 30 milligrams daily. o Equivalent therapeutic response was demonstrated for saffron,

imipramine 100 milligrams daily, and fluoxetine at 20 milligrams BID on the HAMD.

• Lavender (Lavendula spp.) o Lavender showed a synergistic effect with imipramine; adding it to

imipramine therapy led to a greater reduction in HAMD rated depression than imipramine alone.129

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

• Borage (Echium amoenum)

o Borage showed limited benefit for depression compared to placebo.130 o There was an initial decrease in HAMD scores, but the benefit was not

maintained after week six of dosing at 375 milligrams daily.

• Ginkgo (Ginkgo biloba) o 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 have proven to be unresponsive to standard drug treatment.131



o Dosing used in depression studies was 40 milligrams to 80 milligrams three times daily of a 50:1 extract standardized to contain 24% ginkgo-flavone glycosides.

o 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.

o It may interact with blood thinners, calcium channel 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.

This clinical tool 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 also has a private practice as an integrative psychiatrist at La Jolla Village Professional Center, La Jolla, California. 1. Gonzalez O, Berry JT, McKnight-Eily L, et al. Current depression among

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http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=&s=ND&pt=100&id=329&fs=ND&searchid=48583572

http://naturaldatabase.therapeuticresearch.com/nd/Search.aspx?cs=&s=ND&pt=100&id=329&fs=ND&searchid=48583572

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