Richard P. Brown, MD

Herbal Treatment of Major Depression: Scientific Basis and Practical Use


	by Scott D. Mendelson, MD, PhD; Boca Raton, FL: CRC Press; 2020
	420 pages • $160.00 (hardcover)

Scott Mendelson, MD, PhD, has written a landmark volume in the Clinical Pharmacognosy series on Botanical Medicines for CRC Press. Why is this a landmark book? It thoughtfully reviews theories of the mechanisms of activity for antidepressants, including ketamine, and lays out the evidence for herbal activity through those mechanisms. Most psychiatrists will be surprised to learn about the anti-inflammatory, antioxidant, anti-diabetic, and 

Book chapters include relevant in vitro studies of the effects of 66 herbs, providing a foundation for understanding preclinical animal studies and human studies of depression. An additional chapter goes into detail about Chinese Herbal Medicine. Another chapter covers specific plant chemical constituents supported by data on their mechanisms of action. The final chapter discusses how to choose herbs, combine herbs, address comorbidities, and augment conventional synthetic pharmaceuticals.

The evidence base for herbal treatments in depression is now growing rapidly. The availability of quality research should help psychiatrists gain confidence and enthusiasm for prescribing herbs for depression. Those who seek options beyond psychotropic medication will have better choices. Pharmaceutical company researchers wanting to expand their consumer base can develop combination formulas or new herbal products based on data in this volume. Botanical researchers will also find it informative.

Many patients can benefit from herbs with gentler action, fewer adverse effects, and some health benefits beyond their antidepressant effects. Ethnopharmacological differences include heightened sensitivity to adverse medication effects among certain populations. For example, people of Asian ethnicity can be more prone to adverse effects from psychotropics than Caucasians. Consumers who educate themselves about herbal treatments can discuss this knowledge with their healthcare providers.

Another barrier to the use of phytomedicinals is the lack of insurance reimbursement. The out-of-pocket cost must be weighed against the potential therapeutic benefits to the patient, in the context of the patient’s financial situation.

Dr Mendelson succinctly discusses not only familiar herbs for depression, such as 

, lavender, hibiscus, lemon balm, chamomile, and many other lesser known phytomedicinals. He also offers some fascinating clinical pearls, such as the use of milk thistle for obsessive-compulsive disorder (OCD). Data suggesting that St John’s Wort could cause insulin resistance may be news to even experienced herbal prescribers.

When you find that your patient is taking unfamiliar herbs for depression, this is the book to reach for. Here you will find the well-documented, clinically relevant information you will need to evaluate and advise your patient. This will also provide a sound basis for your entry into the realm of herbal prescribing to reduce adverse reactions, minimize the use of synthetic medications, augment other antidepressant treatments, and improve patient compliance and outcomes.

Dr Brown is Associate Professor of Clinical Psychiatry at Columbia University Vagalos College of Medicine, New York.

Experts might read this book straight through, but for those who may not be conversant in biochemistry, the dense structure of the scientific information makes it a heavy read. Most readers will find it an excellent reference book for looking up an herb of interest.

Here and there, editing errors make the text less easy to read. Occasional issues are left out, such as the risk of St John’s Wort causing serious phototoxic rash. For this reason, clinicians should consult more than one source for herbal information, particularly regarding adverse effects.

The clinical utility of the book could have been enhanced by providing some guidance regarding identification of reliable, quality herbal product brands. This is challenging, particularly because companies often change the source or content of their products. This is a difficult and controversial area, but for many herbals, only a few companies manufacture and test their product properly. Furthermore, inferior look-alikes appear to ride on the coattails of high-quality products.

However, these omissions are minor compared to the conceptual and practical steps forward that are represented in this book. Since two thirds of psychiatric patients use alternative approaches, psychiatrists and other health professionals need more information to help patients attain their treatment goals. Phytomedicines can be more helpful than many psychiatrists realize. Overall, they cause fewer adverse effects and are more eco-friendly (causing less pollution than synthetic psychotropics).

I highly recommend this book for psychiatrists and other health professionals treating depression. Furthermore, phytopharmaceutical researchers interested in developing new treatments will find valuable ideas to pursue.

Articles

Many patients can benefit from herbs with gentler action, fewer adverse effects, and some health benefits beyond their antidepressant effects.

Autonomic nervous system dysfunction is associated with most disorders seen in pediatric and adult psychiatric practice, including anxiety disorders, depression, PTSD, hostility and aggression, attention deficit disorders, and autism spectrum disorder. Increasing the underactivity of the parasympathetic branch and correcting the erratic or overactivity of the sympathetic branch can improve stress resilience and ameliorate psychological and physical symptoms.

Although prescription medications (eg, anxiolytics, antidepressants, antipsychotics) can dampen overactivity of the sympathetic nervous system (SNS), they cannot correct underactivity of the parasympathetic nervous system (PNS). Most parasympathetic pathways are contained in the vagus nerves, the 10th cranial nerves, whose extensive branches innervate all internal organs and glands. The development of measures (respiratory sinus arrhythmia, and heart rate variability) of SNS and PNS activity made it possible to assess the effects of interventions such as breathing practices on autonomic activity and to document the association between improvements in sympatho-vagal balance and reduction in psychiatric symptoms.

 The Polyvagal Theory, articulated by Stephen Porges,

 proposes that the vagal nerves are major conduits for bidirectional communication between the brain and the body.

Studies have shown that voluntarily regulated breathing practices (VRBPs) can significantly improve symptoms of anxiety disorders, trauma- and stressor-related disorders, depressive disorders, and other conditions.

 VRBPs can also be used to restore feelings of meaningful connection, bonding, and love for patients who experience states of disconnection or emotional numbing-common sequelae of trauma and loss. Certain breathing practices can facilitate the psychotherapeutic process by reducing anxiety and defensiveness.

 Patients with long-standing psychological and somatic PTSD symptoms responded to VRBPs after years of no response to traditional psychotherapy and psychoanalysis.

 Their sexual function, body perceptions, sense of self, pain syndromes, and other symptoms normalized.

Furthermore, clinicians can use VRBPs to reduce their own level of stress and to enhance empathic abilities.

Neuroanatomic substrate for effects of VRBPs on sympatho-vagal balance

In 2005, we proposed a neurophysiological model to account for the observed clinical effects of VRBPs on sympatho-vagal balance and psychological symptoms.

 Specific VRBPs entail changing the pattern of breathing, thereby changing the interoceptive messages sent through vagal afferent pathways (from the peripheral to the CNS), via brainstem nuclei to the limbic system, hypothalamus, thalamus, prefrontal cortex, insular cortex, and networks involved in perception, interpretation, emotion regulation, and cognitive function (

). The respiratory system is rich in stretch receptors (eg, inside alveolar walls, thoracic musculature, diaphragm), bronchial airways, chemoreceptors, and baroreceptors. Two-way neural pathways between the respiratory system and the brain are of necessity strong and rapid. Interoceptive information derived from breathing patterns has global effects on brain function with the potential to rapidly change how we feel and think.

The polyvagal theory and social engagement systems

According to polyvagal theory, the hierarchical organization of the autonomic stress response system contains 3 evolutionary levels of development. The oldest, evolutionarily, are the unmyelinated vagal fibers, which carry signals that induce defensive states associated with death feigning, freezing, or dissociation. The second level of development, the sympathetic system, orchestrates fight or flight (approach or avoid) responses. The third and highest evolutionary level is the myelinated vagus found only in mammals. A mere 3% of vagal fibers, the myelinated vagus, enables the social engagement system, bonding, group cooperation, communication, and love. According to Porges,

 any stimulus that increases feelings of safety can recruit neural circuits that support the social engagement system and inhibit defensive limbic structures. Physiological states characterized by increased vagal influence on heart rate variability support social bonding.

 hypothesized that slow breathing practices (through vagal afferent stimulation) could increase gamma amino-butyric acid (GABA) transmission from the prefrontal cortex (and possibly the insular cortex) to the central nucleus of the amygdala. The inhibitory transmitter, GABA, could modulate the overactivity known to occur in the amygdala in individuals with PTSD, depression, and epilepsy (Figure). In a recent phase 1 mass resonance spectroscopy randomized controlled trial (RCT) of 30 patients with MDD, participation in a 12-week program of Iyengar yoga and coherent breathing resulted in significant increases in thalamic GABA levels and heart rate variability, which correlated with significant reductions in depression.

Slow breathing practices increase vagal influence on heart rate variability

Hundreds of breathing practices are described in ancient and modern texts. In brief, they can be divided according to respiratory rate, relative ratio of the length of 4 breath phases (inhalation, pause, exhalation, pause), and forcefulness of breathing. In general, slow, gentle breathing is calming and increases parasympathetic tone; rapid, forceful breathing is activating and increases sympathetic tone. The 

 summarizes breath practices commonly used in the US. The characteristics of VRBPs that increase vagal influence on heart rate variability and that tend to induce calm, relaxed states; reduce defensive reactions; and activate the social engagement system are slow rate, prolonged expiratory phase, and airway resistance. Three of the most clinically useful slow VRBPs (3 to 10 breaths per minute, cpm) are Qi Gong breath 4-4-6-2, coherent breathing, and breath moving.

. Paces breath cycle: 4 counts on the inhale, 4 to pause, 6 on the exhale, and 2 to pause. This calming practice activates the PNS. It can be used in combination with a Qi Gong posture to rapidly reduce anxiety, rage, and suicidal thoughts.

. Gentle natural breathing in and out through the nose with equal length of inspiration and expiration at a rate that optimizes sympatho-vagal balance (heart rate variability), between 4.5 and 6 cpm for most adults. For more sedative effects at bedtime, the length of exhalation is doubled. This is the most clinically useful practice because it is easy to learn, safe for most people, and induces a mental state of emotional calmness with mental alertness and enhanced cognitive processing. It can be done unobtrusively with eyes open walking, during everyday activities (eg, reading, writing, working), and in public. Consequently, it can be used throughout the day without attracting attention. Also it creates a relaxed alert state that is optimal for daytime functioning.

Adverse reactions are rare. However, in patients with severe symptomatic asthma, initiating slow breathing may cause narrowing of the airways and may exacerbate breathing problems. We found that teaching asthmatics to do breath moving prevents this temporary bronchiolar constriction during slow breathing practices.

 is an advanced practice in Qi Gong and other traditions, wherein one uses the imagination to move the breath and attention to different parts of the body in circuits.

 Breath moving can augment the benefits of coherent breathing in the treatment of psychological conditions, physical injuries, and pain. It also prevents transient bronchiolar constriction during slow breathing practices in patients with respiratory problems such as severe asthma.

The studies of vagal nerve stimulation, paced breathing, and VRBPs that support the proposed neurophysiological model for the effects of VRBPs on the brain were reviewed in 2005.

 Subsequently, a review of VRBPs by Brown, Gerbarg, and Muench

 in 2013, which included multi-modal mind-body programs wherein breath practices were a major component of the intervention, identified 5 RCTs in persons under stress but without a psychiatric diagnosis. All 227 participants showed significant improvements in perceived stress, insomnia, anxiety, depression, and anger. In one of these studies, paced breathing at 8 cpm before an electric shock increased parasympathetic tone (high-frequency heart rate variability), but pacing at 15 cpm decreased heart rate variability.

In studies of patients with anxiety and insomnia, 4 RCTs (N = 190) and one nonrandomized controlled trial (N = 91) found significant improvements in anxiety, fear, and insomnia. Three RCTs (N = 152) and one nonrandomized controlled trial (N = 183) showed highly significant improvements on standardized measure of PTSD (

 < .007 - <.001). The groups studied were survivors of mass disasters (tsunami and war), victims of intimate partner abuse, and disabled veterans with chronic treatment-resistant PTSD. Two RCTs (total N = 127) documented significant improvements in patients with diagnosed depression.

 included one study of kapalabhati and one of alternate nostril breathing that showed benefits in ADHD. Since these reviews, an RCT of 21 veterans with PTSD found significant improvements in PTSD, anxiety, and hyperarousal symptoms.

 This study replicated the methods (with additional biomarkers) and findings of an earlier 6-month RCT of 31 Vietnam veterans with severe treatment-resistant PTSD, who responded to a similar intervention with an effect size of 0.9 for change on the Clinician Administered PTSD Scale (CAPS) at week 6.

Combining breathing techniques with conventional treatments

Breathing practices enhance conventional treatments. The following are a few examples. Many people have difficulty learning mindfulness and other meditation-based techniques because their level of anxious ruminations is so high that they cannot focus productively on anything else. One advantage of breath practice is that it does not matter what the mind is doing. If the person simply paces his or her breathing to 5 cpm using a sound track, the anxious ruminations will quiet down and cognitive functions will improve. Once the mind is quiet and calm, it is much easier to focus on mindfulness, meditation, and psychotherapy.

Although cognitive behavioral therapy is beneficial in many cases, it has some limitations. A top-down cognitive approach is not always able to control anxiety. It takes many sessions and considerable effort to control intense fears and other emotions. Coherent breathing, as a bottom-up approach, is more effective because it bypasses intellectual processing and utilizes more rapid and powerful pathways between the brainstem and the emotion regulatory circuits.

Once coherent breathing has shifted a patient out of the sympathetically driven defense mode and into the more parasympathetic social engagement mode, it becomes easier to engage in any form of therapy, to be more open and trusting, and to cognitively process whatever is discussed in treatment. In addition, if overwhelming emotions arise, the breath practice can be used for self-regulation during sessions.

There are no known adverse interactions between slow therapeutic breath practices and medications. The only adverse medication interaction we are aware of can occur with rapid breath practices that increase urinary output and therefore can lower lithium levels. Breathing practices can augment the benefits of medication and, in many cases, reduce the dose of medication needed (eg, sedative hypnotics, anxiolytics).

Alex, a 20-year-old college junior, consulted a psychiatrist for help with anxiety, limited symptom attacks, insomnia, and inability to focus on preparing for final exams. He appeared to be on the verge of tears, and his right leg jiggled up and down continuously. The history revealed a pattern of low-grade anxiety with increased severity in reaction to academic pressures.

Previous treatments included benzodiazepines and sertraline. Alex did not like to take medication and was eager to learn a breathing practice that was offered as an alternative. He was taught coherent breathing paced at 5 cpm with a CD chime track. Within 5 minutes, he appeared physically relaxed and his leg stopped shaking. After another 15 minutes, he resumed normal breathing and opened his eyes. Alex said that the anxiety was gone, the worry thoughts stopped, and he felt calmer and more relaxed than he had in a very long time. He agreed to practice the breathing for 20 minutes twice a day during stressful times and otherwise once a day.

The psychiatrist also encouraged him to do shorter periods of coherent breathing whenever he felt stressed, such as waiting for a test to begin. She also advised him that doubling the length of his exhale when he practiced at bedtime would help him fall asleep. The following week Alex came to the office smiling. He had downloaded a breath-pacing app on his iPhone and used coherent breathing to manage stress and quickly fall asleep.

Breathing practices are being studied for the treatment of depression, anxiety, trauma, and schizophrenia. One current trend-when funding is available-is to include biological markers (eg, inflammatory markers, heart rate variability, oxytocin, cortisol), brain imaging (eg, functional MRI, mass resonance spectroscopy), and EEG data that provide more information about the underlying psycho-neuro-immuno-endocrine processes involved in the clinical changes that occur with mind-body techniques. The use of breathing practices in the treatment of stress-related and immune-related medical conditions (eg, cardiovascular disease, inflammatory bowel disease, diabetes, dementia) is developing. Breath practices for children is an area with tremendous potential for improving emotion regulation, behavior, learning, and social/interpersonal development.

To date, although the number of yoga programs in schools is growing, the research on mind-body programs for children has received relatively little support. Most of the studies show positive results, but they are small and preliminary. We have observed that children learn breathing practices very easily and are eager to use them because they like to feel calmer, to control their emotions and behaviors, to put themselves to sleep, and to reduce their anxiety when taking tests or performing in arts or sports. They also enjoy teaching the breathing practices to their friends and family (see Chemung County Project at www.Breath-body-mind.com).

Slow VRBPs are noninvasive, easy to learn, and generally safe for treating patients with symptoms of anxiety, insomnia, depression, stress- and trauma-related disorders, ADHD, schizophrenia, and substance abuse. A small but growing literature supports the benefits of VRBPs as solo or adjunctive treatments. Significant improvements in emotion regulation and stress response have been attributed to the effects of afferent signals from the respiratory system, transmitted by vagal afferents to the hypothalamus, limbic system, thalamus, and prefrontal and frontal cortex. Reduced sympathetic activity and defensive reactions, in tandem with increased activity of the parasympathetic and social engagement systems, have been implicated. Breath practices have the potential to open a portal to correct imbalances of the stress response systems and to facilitate emotion regulation, social engagement, bonding, and recovery from trauma.

Dr. Gerbarg is Assistant Clinical Professor of Psychiatry, New York Medical College, Valhalla, NY. Dr. Brown is Associate Clinical Professor of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY. Drs. Gerbarg and Brown are co-editors and chapter co-authors with Dr. Philip R. Muskin of the upcoming 

Complementary and Integrative Treatments in Psychiatric Practice

 from the American Psychiatric Association Press. The authors report that they are consultants on NCCAM Grant RO1 AT007483, they teach breath-body-mind workshops, and they receive royalties for books on this topic.

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The Healing Power of the Breath. Simple Techniques to Reduce Stress and Anxiety, Enhance Concentration, and Balance Your Emotions

Yoga and neuronal pathways to enhance stress response, emotion regulation, bonding, and spirituality. In: Horowitz EG, Elgelid S, eds. Yoga Therapy: Theory and Practice

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Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, Self-Regulation

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 Seppala EM, Nitschke JB, Tudorascu DL, et al. Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: a randomized controlled longitudinal study. 

 Carter JJ, Gerbarg PL, Brown RP, Ware R. Multi-component yoga breath program for Vietnam veteran posttraumatic stress disorder: randomized controlled trial. 

Slow voluntarily regulated breathing practices are noninvasive, easy to learn, and generally safe for treating patients with symptoms of anxiety, insomnia, depression, stress- and trauma-related disorders, ADHD, schizophrenia, and substance abuse. 

Neurobiology and Neurophysiology of Breath Practices in Psychiatric Care

Top-down approaches, in which the mind of the therapist engages the mind of the patient, have dominated traditional psychotherapy and psychoanalysis. However, the effects of mind-body approaches on cognitive and emotional processes show that integrating bottom-up with top-down modalities can be highly effective-even in acute or chronic severe treatment-resistant conditions, such as trauma- and stressor-related disorders.

 Multimodal and integrative treatments have been found to rapidly reduce symptoms of anxiety, depression, and PTSD in numerous studies.

 Furthermore, with 20 minutes of practice 5 days per week, the improvements persist at long-term follow-up.

In a world that is straining our stress response systems with pressure, trauma, uncertainty, and threats, the autonomic system spends too much time in the fight/flight zone. The tide of distress and dysfunction, which is overwhelming health care systems, will not be stopped by medications alone, nor by one-on-one therapies or expensive high-tech treatments.

Mind-body interventions that are less costly and low-risk can provide long-term symptomatic relief to large populations, including survivors of natural and man-made disasters.

 Identifying best practices for prevention and treatment of stress-related disorders could substantially benefit public health. Improvements in technology-for example, measures of heart rate variability-provide ways to evaluate and enhance the effects of mind-body interventions on stress response.

Voluntarily regulated breathing practices

Mind-body practices include movement, breathing, and meditation. According to polyvagal theory, states that are characterized by increased influence of the parasympathetic myelinated pathways of the vagal nerves increase feelings of safety and support social engagement and bonding while inhibiting defense limbic system reactions.

 Within minutes, slow, voluntarily regulated breathing practices (VRBPs)-in the range of 4.5 to 6 breaths per minute for most adults-will lead to a state of sympatho-vagal balance characterized by emotional calmness and mental alertness.

 This state improves emotional processing, cognitive functioning, and the capacity for positive relationships.

Respiration is the only autonomic function that can be easily changed through voluntary effort. The voluntary control of breathing provides a portal for interoceptive communication between the body and the brain. Interoception is the perception of sensations or other signals that carry information about the internal state of the body.

Through “interoceptive messaging” of signals from the respiratory system, VRBPs can induce rapid, widespread effects on emotional states; perceptions; subjective experience of the body; cognitive processes; and the capacity for social engagement, connectedness, bonding, empathy, and love.

Simple VRBPs can be easily integrated into psychotherapy and mindfulness or cognitive therapies. Such practices can be adapted for individual or group interventions in clinics, hospitals, schools, and after-school programs. Further information on the use of VRBPs can be found at 

This article was originally posted on 2/8/2016 and has since been updated.

Dr Gerbarg is Assistant Clinical Professor of Psychiatry at New York Medical College in Valhalla, NY. Dr Brown is Associate Clinical Professor of Psychiatry at Columbia University Medical Center in New York. Both Dr Gerbarg and Dr Brown are members of the Caucus on Complementary and Integrative Treatments of the American Psychiatric Association (APA). They have co-authored articles and award-winning books and have provided courses on complementary and integrative medicine at APA meetings.

 Gard T, Noggle, JJ, Park CL, et al. Potential self-regulatory mechanisms of yoga for psychological health. 

 Gerbarg PL, Wallace G, Brown RP. Mass disasters and mind-body solutions: evidence and field insights. 

 [book and CD-ROM]. New York: Shambhala Press; 2012.

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. New York: Guilford Press; 2008:272-290.

 Gerbarg PL, Brown RP. Yoga and neuronal pathways to enhance stress response, emotion regulation, bonding, and spirituality. In: Horowitz EG, Elgelid S, eds. 

Top-down Plus Bottom-up Integrative Treatments in Psychiatry

[[{"type":"media","view_mode":"media_crop","fid":"15605","attributes":{"alt":"integrative psychiatry","class":"media-image media-image-right","id":"media_crop_1866071097875","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"746","media_crop_rotate":"0","media_crop_scale_h":"201","media_crop_scale_w":"160","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":" ","typeof":"foaf:Image"}}]]After decades of mind/brain-focused subspecialization, psychiatry is now reconsidering the whole person. “Integrative medicine” is being used to denote the strategic combining of standard treatments (eg, medication, psychotherapies) with evidence-based complementary and alternative approaches (eg, herbs, nutrients, acupuncture, neuro-therapy). “Integrated medicine” refers to the practice of using a multidisciplinary treatment team (physicians, psychologists, social workers, and occupational and physical therapists). The goals of both 

 are to address the biological, psychological, and social needs of the patient.

This article highlights evidence-based treatment with herbs and nutrients with good tolerability and potential benefit when integrated into psychiatric practices. The other two articles in this Special Report are intended to refresh and update your knowledge of nutritional and metabolic disorders commonly encountered in psychiatric patients. Psychiatrists can diagnose conditions such as vitamin deficiencies, nutrient deficiencies, 

, and they can treat or refer patients with these ailments.

 have proposed that integrative mental health (a subdivision of integrative medicine) encompass mainstream mental health treatments, evidence-based complementary and alternative approaches, healthy lifestyle changes, and socio-cultural issues. The evolving concept of integrative mental health appears to encompass the goals and practices of integrated medicine.

Modern medicine is probing the biological bases of nutritional supplements and herbs to understand their therapeutic actions. Identifying active constituents and improving extraction processes will allow further development of natural combinations and synthetic analogues and consequently will expand treatment options.

B vitamins, folate, S-adenosylmethionine.

 Depression and nonresponse to antidepressant medication have been associated with B vitamin and folate deficiencies. Patients with a history of substance abuse, poor diet, chronic illness, and age-related decline are at greater risk for vitamin B and folate deficiencies. Methylation, the transfer of methyl groups, is essential for production of key cellular components such as proteins, phospholipids, and neurotransmitters. S-adenosylmethionine (SAMe) is the body’s most active methyl donor: folate and vitamin B12 are essential cofactors in the methylation cycle. Antidepressant augmentation with folic acid or folinic acid was shown to significantly improve scores on the 

SAMe has been found to be more effective than placebo and as effective as standard antidepressants for treating depression. Compared with prescription antidepressants, SAMe has fewer adverse effects (eg, no weight gain or sexual dysfunction) and a faster onset of action, and as an adjunct, SAMe increases response to antidepressants.

SAMe deficiency occurs often in patients with Parkinson disease, particularly in those treated with L-dopa, which depletes SAMe and leads to treatment-resistant depression. In such cases, high doses of SAMe effectively alleviate depression and, in many cases, improve parkinsonian symptoms.

 In addition to maintaining neuronal cell membrane fluidity, 

 modulate neurotransmitter signaling, calcium ion influx, and secretion of cytokines. Modern dietary habits may be the cause of omega-3 fatty acid insufficiency. Some findings suggest that omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) may be beneficial in unipolar and bipolar depression.

The evidence is different for MDD. Significant methodological problems and publication bias were found in 13 randomized controlled trials reviewed in a meta-analysis.

 Although the proportions of omega-6 fatty acids and omega-3 fatty acids in cell membranes may contribute to the development of depression, the evidence that omega-3 fatty acids contribute significantly to the treatment of MDD is weak.

In perinatal depression, omega-3 fatty acid supplementation is especially effective in improving mood, replenishing depleted fatty acid stores, and supporting neonatal and postnatal brain development. An initial randomized controlled study of 

 found that omega-3 fatty acids were safe and effective.

-acetylcysteine, a precursor to the major antioxidant glutathione, was found to augment mood stabilizers in patients with bipolar disorder.

 In a double-blind, randomized, placebo-controlled study of 140 patients with chronic schizophrenia, 

-acetylcysteine reduced akathisia and negative symptoms on the Positive and Negative Syndrome Scale.

 Modulation of glutamate may contribute to the demonstrated benefits of 

-acetylcysteine in depression, panic disorder, obsessive-compulsive disorder (OCD), bipolar depression, and 

Preliminary randomized clinical trials suggest that inositol, a phospholipid precursor, may be a useful adjunctive treatment for bipolar disorder and panic disorder, as well as for depression, OCD, bulimia nervosa, and binge eating disorder, although the evidence for the last 4 is limited.

 In persons with zinc, iron, or copper insufficiency, supplementation may be helpful in treating depression as well as hyperactivity and impulsiveness in ADHD.

Concerns about potential herb-drug interactions prevent many physicians from integrating plant extracts into psychiatric practice. However, most of the herbs that are useful in psychiatric patients have very few, if any, significant adverse effects.

Adaptogens are herbs whose roots, leaves, petals, stamen, and/or berries contain biologically active constituents that when extracted enhance the ability of organisms to resist numerous kinds of stressors-including physical activity, psychological stress, toxic exposures, excess heat or cold, infections, inflammation, hormonal changes, and malignancies. To qualify as an adaptogen, the extracts must be low in adverse effects and well tolerated by most people. More recently, these plant extracts are being redefined as metabolic regulators.

(Rhodiola rosea). This ancient medicinal herb produces over a hundred bioactive compounds in its roots that act as antioxidants, antimicrobials, mitochondrial energy enhancers, antidepressants, selective estrogen receptor modulators, and more. Extensive research has shown that high-grade extracts can improve cellular repair and physical and intellectual performance, particularly under stress. Evidence supports the role of adaptogens in neuroendocrine regulation of the hypothalamic-pituitary-adrenal axis and in gene expression of key mediators of stress-induced signal transduction pathways, such as neuropeptide Y, nitric oxide, membrane-bound G protein signaling pathways, stress-activated protein kinase, and molecular chaperones such as 

 reduced extrapyramidal adverse effects of neuroleptics.

, which grows in northern China and Siberia, improves fatigue, sleep, stamina, mood, and cognitive function with very few adverse effects. One study showed it augmented lithium, reduced conversion to mania, and increased remission rates after 6 weeks.

 roots and seeds are used to reduce stress, fatigue, bipolar depression, tension, anxiety, and weakness. 

 is also useful in reducing the adverse effects of other medications, such as antidepressants and antipsychotics. Adaptogen combinations such as ADAPT, with R 

 extracts increase blood flow, abstract thinking, reaction time, accuracy, and working memory at daily doses of 300 to 800 mg. However, methodological limitations have been found in studies of ginseng.

 Moreover, anxiety, insomnia, tachycardia, GI symptoms, headache, and reduced platelet aggregation have been reported with the 

 High-quality St John’s wort extracts have been demonstrated to be effective in the treatment of mild to moderate depression and somatoform disorder, with possible benefits in seasonal affective disorder.

 However, St John’s wort has also been shown to induce cytochrome P-450 3A4, 2C9, and 1A2 isozymes and P-glycoproteins in humans.

 It can affect serum levels of many medications, including immune suppressants used to prevent organ rejection in transplant patients, digoxin, warfarin, oral contraceptives, theophylline, and protease inhibitors.

In addition, St John’s wort can cause phototoxicity, 

, and serotonin syndrome, particularly in combination with prescription antidepressants. Therefore, it is incumbent on the physician to be knowledgeable about brand quality, inquire about the use of St John’s wort, check for potential herb-drug interactions, and inform the patient of potential risks.

Nutritional supplements, particularly the use of daily vitamins has become routine practice. Complementary and alternative medicine approaches, such as hypnosis and acupuncture have gradually gained acceptance in mainstream medical practice. Thousands of articles are published each year on complementary, alternative, and integrative treatments. Rather than being left behind, physicians can safely integrate these valuable treatments into their clinical work by identifying the most effective and best-documented treatments and by learning how to minimize the risks of adverse reactions.


Dr Gerbarg is Assistant Professor in Clinical Psychiatry, New York Medical College. She is a member of the American Psychiatric Association Task Force on Complementary and Integrative Medicine and an American Botanical Council Board Member. Dr Brown is Associate Professor in Clinical Psychiatry, Columbia University College of Physicians and Surgeons, New York. He is also a member of the American Psychiatric Association Task Force on Complementary and Integrative Medicine. Dr Brown and Dr Gerbarg coauthored 

Non-Drug Treatments for ADHD: New Options for Kids, Adults, and Clinicians

The Healing Power of the Breath: Simple Techniques to Reduce Stress and Anxiety, Enhance Concentration, and Balance Your Emotions

 (Shambhala Publications, Inc; 2012); and over 40 articles and book chapters on complementary, alternative, and integrative treatments. They wrote 

How to Use Herbs, Nutrients, & Yoga in Mental Health

 (WW Norton and Company, Inc; 2009) with Dr Philip Muskin.

 Sarris J, Glick R, Hoenders R, et al. Integrative mental healthcare White Paper: establishing a new paradigm through research, education, and clinical guidelines. 

http://www.inimh.org/files/IMH%20White%20Paper.pdf

 Bottiglieri T. Folate, vitamin B12, and S-adenosylmethionine. 

 Hallahan B, Hibbeln JR, Davis JM, Garland MR. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial. 

Bloch MH, Hannestad J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. 

 Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. 

 Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia-a double-blind, randomized, placebo-controlled trial. 

Berk M, Copolov DL, Dean O, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder-a double-blind randomized placebo-controlled trial. 

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) versus fluoxetine to lithium for the treatment of bipolar disorder in adolescents: a randomized, double-blind trial. 

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This article highlights evidence-based treatment with herbs and nutrients with good tolerability and potential benefit when integrated into psychiatric practices.

Richard P. Brown, MD

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