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Psychosomatics 2020:-:-–- ª 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved. Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com Review Article Psychoso Complementary Medicine and Natural Medications in Psychiatry: A Guide for the Consultation-Liaison Psychiatrist Sarah Berman, M.D., David Mischoulon, M.D., Ph.D., Uma Naidoo, M.D. Background: Complementary and Alternative Medicine (CAM) is commonly and increasingly used in America and worldwide and can include both pharmacologic (e.g., vitamins and supplements) and non- pharmacologic (e.g., yoga) interventions. These ther- apies may be of interest to patients who desire “natural” alternatives or complements to standard treatments. CAM may be used by patients, with or without supervision from a licensed medical profes- sional, to treat psychiatric conditions. Objective: To provide an overview of more commonly used CAM in- terventions that have relevance to mental health care providers, particularly consultation-liaison psychiatrists, and to describe the indications, safety, and dosing of these treatments. Methods: We searched PubMed to identify articles that described the uses, safety, mecha- nisms, and recommendations for CAM therapies in matics -:-, - 2020 relation to the treatment of psychiatric conditions. Arti- cles most relevant to this review were included, with a preferential focus on meta-analyses and systematic re- views. Results: We summarized common CAM thera- pies that have shown efficacy for the treatment of psychiatric conditions. These therapies include natural medications, nutritional psychiatry, light therapy, yoga, and exercise. Conclusions: Certain CAM interventions may be effective as monotherapies and/or as adjunctive treatments for psychiatric conditions. However, they may also have safety risks, contraindications, and/or interactions with medications. It is therefore important for physicians and other mental health care pro- fessionals to inquire about patient use of CAM and to understand the indications, safety, and dosing of these therapies. (Psychosomatics 2020; -:-–-) Key words: depression, anxiety, dementia, mental health, nutrition. Received December 2, 2019; revised April 10, 2020; accepted April 10, 2020. From the Department of Psychiatry, Harvard Medical School (S.B., D.M., U.N.), Boston, MA; Depression Clinical and Research Program (D.M.), Massachusetts General Hospital, Boston, MA; The Bulfinch Program (U.N.), Massachusetts General Hospital, Boston, MA. Send correspondence and reprint requests to Sarah Berman, MD, Department of Psychiatry, HarvardMedical School, 25 Shattuck Street, Boston, MA 02115; e-mail: bermsarah@gmail.com ª 2020Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved. INTRODUCTION Complementary and alternative medicine (CAM) en- compasses all healing therapies and practices other than those of the predominant health system and can include herbal remedies, physical practices (yoga, qigong), and procedures (acupuncture).1 CAM use is common in United States. Data from the 2012 National Health Interview Survey show that 33.2% of American adults and 11.6% of children use some form of CAM.2,3 The most common CAM therapy used was dietary supple- ments, with 17.7% of surveyed adults reporting use, while postural exercises such as yoga have increased from 5.8% in 2002 to 10.1% in 2012.2 A more nascent area is nutritional psychiatry, where individuals use actual food as an adjunctive measure to feel better and to improve mood and anxiety symptoms.4 This last www.psychosomaticsjournal.org 1 mailto:bermsarah@gmail.com http://www.psychosomaticsjournal.org Medications in Psychiatry Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com area is becoming increasingly integrated in the practice of lifestyle medicine and mental health. Despite widespread use and increasing popularity, many patients do not disclose CAM use to their phy- sicians.5,6 Given these realities, physicians and other health care providers must understand the evidence and safety of these therapies and routinely inquire about their use during patient interviews. The purpose of this brief review is, therefore, to explore some of the better studied and more popular pharmacological and non- pharmacological CAM therapies that may be used for psychiatric conditions and encountered by psychiatrists on consultation-liaison services and/or in outpatient practice. While not exhaustive or seeking to provide novel insights in the way of a meta-analysis or sys- tematic review, we will give the psychiatrist a good framework for deciding whether and when to recom- mend these treatments and how to present them to patients. NATURAL MEDICATIONS Ginkgo (Ginkgo biloba, EGb) The ginkgo tree (Ginkgo biloba) is native to China, and its leaves are commonly used in traditional Chinese medicine.7 Ginkgo has been studied in treatment of dementia and cognitive impairment with mixed evi- dence supporting its efficacy. Generally, gingko is not thought to be effective in healthy adults in the pre- vention of cognitive decline nor in improving cognitive function. A 2002 randomized, controlled trial (RCT) of 130 older adults with healthy cognition found no evi- dence supporting the use of ginkgo for memory or cognitive function.8 Two large-scale RCTs found that Ginkgo is not effective for the prevention of dementia and cognitive decline. The Ginkgo Evaluation of Memory study, an RCT of over 3000 older adults without dementia, found no differences in cognitive decline with ginkgo treatments as compared to pla- cebo.9 Similarly the GuidAge trial with about 2800 older adults with memory complaints found that long- term use of ginkgo extract did not reduce risk of de- mentia.10 In adults with cognitive impairment, results have generally been mixed to positive. A 2009 review of 36 trials of ginkgo use in patients with age-related cognitive impairment and dementia found inconsistent results and that many trials were small and of poor 2 www.psychosomaticsjournal.org design and bias that could not be excluded.11 However, 2 more recent RCTs in Eastern-European older adults with dementia and neuropsychiatric symptoms found that gingko was superior to placebo.12,13 In 2019, the Asian Clinical Expert Group on Neurocognitive Dis- orders recommended the use of ginkgo extract in the treatment of dementia.14 A 2016 review by Yang et al.15 found that ginkgo treatment was comparable to regis- tered therapies (e.g., donepezil, rivastigmine, mem- antine) on cognitive function and reported that ginkgo plus registered therapies were superior to registered therapy alone. Ginkgo’s neuroprotective properties may underlie its therapeutic effects. It has been shown to protect neurons from death from noxious stimuli and from oxidative stress.16 Ginkgo extract is thought to affect intracellular apoptosis signaling pathways and has been shown to reduce apoptosis induced by hydroxyl radicals.16,17 It also is thought to inhibit platelet- activating factor and facilitate blood flow, which may be the reason behind the beneficial effects seen in vascular dementia.17 In addition, Ginkgo has effects on dopaminergic, serotonergic, cholinergic, gamma- aminobutyric acid-ergic, and glutamatergic systems.16 Ginkgo use may reduce the efficacy of anticon- vulsants via cytochrome P450 (CYP) interactions, thus increasing the risk of seizures.7 It also has reported theoretical interactions with anticoagulants, antiplatelet drugs, calcium channel blockers, trazodone, and monoamine oxidase inhibitors.17 Ginkgo may inhibit MAO and has a theoretical risk for serotonin syndrome when taken with other serotonergic medications.17 Finally, ginkgo may increase risk of stroke, transient ischemic attacks, and bleeding and has been reported to cause arrhythmias and allergic reactions.7,17,18 Typi- cally 240 mg per day in single or divided doses is rec- ommended,but doses between 80 mg and 730 mg per day have also been used.14,17 Treatment should be reserved for patients with evidence of dementia and should be administered for at least 4–6 weeks before benefits are usually seen, with some reports suggesting to allow this up to 1 year of treatment to better deter- mine impact on dementia.17,19 Kava Kava (Piper methysticum) Kava is extracted from the roots of Piper methysticum, a plant originating in the South Pacific,20,21 where it has Psychosomatics -:-, - 2020 http://www.psychosomaticsjournal.org Berman et al. Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com been traditionally consumed for religious, medicinal, and social purposes.22 Kava has been studied in the treatment of anxiety disorders with promising, yet inconclusive, results. A 2005 meta-analysis by Witte et al.23 found that kava is effective for nonpsychotic anxiety. Conversely, a more recent meta-analysis by Ooi et al.24 did not find efficacy for kava compared with placebo. Other reviews favored kava as potentially effective for treating anxiety.20,21 Interestingly, data suggest that kava may be more effective for younger adults and females.21,23 Most recently, 58 patients with anxiety were given kava or placebo in a RCT and found that kava reduced anxiety symptoms compared with placebo, with gamma-aminobutyric acid poly- morphisms potentially moderating the response.25 Kava may exert its anxiolytic effect by enhancing ligand binding to gamma-aminobutyric acid-A receptors and inhibiting voltage-gated sodium and calcium chan- nels, similar to benzodiazepines, but in a way that is not affected by flumazenil, a benzodiazepine antagonist.20,22 Kava may also increase acetylcholine, reduce reuptake of dopamine and norepinephrine in neurons, and have monoamine oxidase inhibitors-B effects.22 The major safety concern with kava is its risk of hepatotoxicity, especially if taken for a long period of time (.8 wk).21,24 As such, trials using kava have only studied outcomes for short-term administration, and individuals considering kava should be advised to view it as a short-term therapy and not as a long-term so- lution to their anxiety. Certain kavalactones are toxic, especially those in the aerial portions of the plant, and variations in preparation and lack of regulation are thought to be the reasons for cases of toxicity.20 In the South Pacific, where the plant is more commonly consumed, kava is generally well tolerated, suggesting that risk of hepatotoxicity may be due to genetic vari- ability between South Pacific Islanders and those from outside the South Pacific.21 Likewise, other reports have suggested that extraneous contaminants may be responsible for cases of liver toxicity.26 Kava is also known to cause a dermopathy of the arms and upper back.22 Other milder side effects include gastrointes- tinal (GI) upset, fatigue, headaches, muscle aches, and shakiness.21 Generally, doses above 120 mg per day for more than 3 months are not recommended.22 Liver function should be monitored, and caution should be taken in patients with liver disease or who are taking medications that are metabolized by the liver.27 Psychosomatics -:-, - 2020 Omega-3 Fatty Acids (Fish Oil, Eicosapentaenoic Acid, Docosahexaenoic Acid) Omega-3 fatty acids are essential polyunsaturated fatty acids obtained from the diet and found in fish, nuts, and seeds.28,29 Consumption can vary around the world, with the American diet, which is relatively low in fish intake, being comparatively deficient in omega-3 fatty acids.30 Omega-3s have grown in popularity in medi- cine because of their benefits to cardiovascular health, so much so that the Food and Drug Administration recently approved omega-3 icosapent ethyl, or Vascepa (Amarin Corp, Dublin, Ireland) for use as an adjunc- tive therapy for adults with hyperlipidemia.31 In psy- chiatry, omega-3s, particularly eicosapentaenoic acid and docosahexaenoic acid, are of interest in the treat- ment of depression, given that observational studies have found that fish consumption and omega-3 intake are inversely related to depressive symptoms.32 Several meta-analyses point to the therapeutic benefit of omega-3s in patients with depression, espe- cially when used to augment standard antidepres- sants.28,33–35 In 2016, Mocking et al.36 found beneficial effects of omega-3s for major depressive disorder (MDD) and also that higher eicosapentaenoic acid dose, rather than docosahexaenoic acid or eicosa- pentaenoic acid:docosahexaenoic acid ratio, was significantly associated with better outcomes. The Ca- nadian Network for Mood and Anxiety Treatments (CANMAT) recommended omega-3 as a second-line monotherapy for mild to moderate MDD and as a second-line adjunctive to antidepressant for moderate to severe MDD based on level one evidence of effi- cacy.29 The American Psychiatric Association Task Force on Complementary and Alternative Medicine in Major Depressive Disorder found that research sup- ports use of omega-3 as an adjunctive treatment for depression.30 Of note, a 2019 meta-analysis of over 41,000 omega-3 trial participants concluded that “long- chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symp- toms.”37 Generally, benefit has been seen to be modest at best and based largely on low-quality evidence.38 Omega-3s are an essential component of the eukaryotic cell membrane, and increased omega-3 content can increase membrane fluidity, which then affects the G-protein-coupled receptors situated across the membrane.39 For example, serotonin receptors are www.psychosomaticsjournal.org 3 http://www.psychosomaticsjournal.org Medications in Psychiatry Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com sensitive to membrane fluidity, and as the fluidity de- creases, the binding of serotonin to the receptor de- creases.39 Through this mechanism, omega-3s may increase serotonergic signaling and alter dopaminergic function which may underlie their antidepressant ef- fects.40 In addition, omega-3s have anti-inflammatory actions, and supplementation may correct the ratio of anti-inflammatory omega-3 over proinflammatory omega-6.40 As depression has been theorized to be an inflammatory state, omega-3s0 anti-inflammatory ac- tions may underlie their antidepressant effect. Furthermore, this inhibition of inflammatory prosta- glandins may in turn increase serotonin release.39 Omega-3 fatty acids are well tolerated with only mild GI symptoms.29 However, there is a concern that omega-3s may induce mania and increase risk for bleeding, and people are usually advised to discontinue omega-3s before undergoing surgery.29,30 Some reports, however, suggest that concerns over bleeding may have been premature.41 Omega-3s should also be taken with caution in people with prostate cancer as some epide- miologic studies have linked fatty acids to the condi- tion, although there is no prospective evidence of causality.34 Doses may range from 1 to 9 g per day of omega-3s, depending on the condition treated, and recommended doses in depression are 1–2 g per day of eicosapentaenoic acid and/or 1–2 g per day of docosa- hexaenoic acid.29,42 S-Adenosyl-L-Methionine S-adenosyl-L-methionine (SAMe) is produced via the one-carbon cycle from folate or folic acid.43 In Europe, it is prescribed for various conditions including MDD, whereas in the United States and Canada, SAMe is sold as an over-the-counter supplement.29 In 2010, the American Psychiatric Association Task Force on Complementary and Alternative Medicine in Major Depressive Disorder found evidence supporting SAMe monotherapy for depression.30 CANMAT on the other hand recommends SAMe as a second-line adjunctive treatment for mild to moderate MDD.29 Although data are relatively limited, studies in the use of adjunctive SAMe have been primarily positive, while SAMe monotherapy has not consistently outperformed pla- cebo.33,34,44A recent study of 107 adults with MDD on antidepressant therapy found that augmentation with SAMe did not outperform placebo in any primary or secondary measures, although this study used lower 4 www.psychosomaticsjournal.org doses of SAMe than previous studies.45 There is some evidence that gender may impact response to SAMe: One study that disaggregated results by sex found that male patients had a significant reduction in depressive symptoms while female patients did not.46 SAMe’s primary function in the body is to meth- ylate DNA, phospholipids, and proteins among others.43 It may have antidepressant effects through modulating neuronal membrane fluidity by methylating plasma phospholipids.43,47 Changes in membrane fluidity may in turn affect membrane receptors and neurotransmitter signaling, including that of mono- amines such as serotonin.39,43 SAMe is also the cofactor in the rate-limiting step in the conversion of tryptophan to serotonin and tyrosine to dopamine and norepi- nephrine, suggesting that low SAMe levels may cause low monoamine levels.43,48 In addition, disturbances in DNA methylation may affect neurodevelopment and contribute to neuropsychiatric diseases.48 Low levels of SAMe may affect this methylation/demethylation ho- meostasis, and supplementation may improve methyl- ation patterns and neurodevelopment.48 SAMe is generally well tolerated, with side effects including GI upset, constipation, lack of appetite, insomnia, sweating, headache, irritability, anxiety, fa- tigue, tachycardia, and restlessness.29,30 In patients with bipolar disorder, SAMemay increase the risk ofmania or hypomania, particularly when given intravenously or intramuscularly, and its use in this population should always be undertaken with caution.34 Oral dosing is typically between 500 and 1600 mg/d, taken in smaller doses with meals over the course of the day for 4–12 weeks.29 Intravenous and intramuscular administrations typically are at doses of 200–400 mg/d for 2–8 weeks.29 St. John’s Wort (Hypericum perforatum) St. John’s wort, or Hypericum perforatum, is a plant that has been used for centuries as an herbal remedy for depression.49,50 Today, it is used as a prescription drug in several European countries and is available as an over-the-counter supplement in the United States.49 Although a 200-patient, multicenter RCT found no difference in efficacy between St. John’s wort and pla- cebo, St. John’s wort has generally been found to be effective in the treatment of depression.51 The 2010, American Psychiatric Association Task Force on Complementary and Alternative Medicine in Major Depressive Disorder found evidence supporting St. Psychosomatics -:-, - 2020 http://www.psychosomaticsjournal.org Berman et al. Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com John’s wort monotherapy for mild to moderate MDD.30 CANMAT recommends St. John’s wort as first-line monotherapy in mild to moderate depression and as a second-line adjunctive treatment for moderate to severe depression.29 A 2017 meta-analysis found that the antidepressant effect as well as the response and remission rates for St. John’s wort were comparable to those of SSRIs, while the discontinuation rate was significantly lower.49 Similarly, a 2016 systematic re- view found that St. John’s wort outperforms placebo and is comparable to antidepressants for mild to moderate depression.50 Mechanistically, St. John’s wort is thought to have nonselective inhibition of serotonin, dopamine, and norepinephrine reuptake while also weakly inhibiting MAO-A and MAO-B.52 It has also been found to upregulate genes involved with inflammation and oxidative stress similar to fluoxetine.52 St John’s wort has numerous important drug in- teractions. Hyperforin, a key component of St. John’s wort, is a potent inducer of CYP3A4, while the hypericin component is a CYP1A2 inducer.49,53 It is also reported to inhibit the actions of other CYP en- zymes.53 It may potentially reduce therapeutic effects of warfarin, HIV protease inhibitors, digoxin, methadone, oral contraceptive pills, and immunosuppressant drugs among others.30,53 Caution should therefore be used when taking St. John’s wort in combination with other medications. Beyond drug interactions, adverse effects such as GI upset, headaches, skin irritation, rash, photosensitivity, and dry mouth have been re- ported.29,49 Its use may also induce mania in patients with bipolar disorder and can cause serotonin syn- drome in combination with other serotonergic drugs.20,29,53 St. John’s wort dosing ranges from 500 to 1800 mg/d for a duration of 4–12 weeks.29 Tryptophan/5-Hydroxytryptophan Tryptophan is an essential amino acid and, via the in- termediate 5-hydroxytryptophan (5-HTP), serves as a precursor to serotonin.34,47 Tryptophan has typically been studied in depression, with much of the research conducted before 1983 and the advent of the SSRIs.34 The results to date have been mixed, with several re- views finding promising yet inconclusive data, citing the small number of studies, many of which are inade- quately powered, and a lack of recent studies.34,47,54,55 However, despite some positive findings, the Psychosomatics -:-, - 2020 CANMAT does not recommend tryptophan for the treatment of MDD as either a monotherapy or to augment antidepressants.29 More recently, a 2013 study of 60 patients with a first depressive episode found that 5-HTP was comparable to fluoxetine through 8 weeks of treatment.56 However, a 2018 RCT of 158 patients with MDD found that combination therapy with SAMe, folinic acid, omega-3 fatty acids, zinc, and co- factors along with 5-HTP did not result in significant improvement in depressive symptoms.57 Tryptophan is believed to play a role in depression and its treatment through involvement in the synthesis of serotonin.47 Tryptophan is consumed in the diet and then converted to 5-HTP and serotonin. Increases in dietary tryptophan and amounts transported across the blood-brain barrier may in turn increase the amount eventually transformed into serotonin.54 Tryptophan and 5-HTP are thought to be well tolerated in normal doses, with GI side effects most commonly reported.54 Serotonin syndrome may occur when used in conjunction with serotonergic drugs.29,54 In addition, combining these supplements with lithium may increase the risk for lithium toxicity.29 Their use has also been found to be associated with Eosinophilia-Myalgia Syndrome, and because of this, 5-HTP was banned in several countries for several years but is available once again after better manufacturing standards were put in place.47,54 Tryptophan doses are typically 2–4 g per day for 3–4 months.29 The dosage recommendation for 5-HTP is generally 200–300 mg per day 2–4 times a day.54 NUTRITIONAL PSYCHIATRY Medication management and varied psychotherapeutic interventions remain the benchmarks of psychiatric treatment; however, they do not fully and adequately treat the burden of depressive disorders.58 Adding the use of nutritional strategies could be therapeutic without the side effects of standard psychopharmacology treat- ments. A meta-analysis of 24 prospective cohort studies found that an adherence to a high-quality (i.e., healthier) diet was associated with a lower risk for depressive symptoms over time.59 Likewise, individuals with depression have a 40% higher risk of developing car- diovascular and metabolic diseases than the general population and as such could benefit from dietary in- terventions.60 The potential for both positive mental and www.psychosomaticsjournal.org 5 http://www.psychosomaticsjournal.org Medications in Psychiatry Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com physical health outcomes without adverse effects asso- ciated with many medications offers a strong argument for evidence-based dietary interventions, such as the Mediterranean diet,61,62 to help lower symptoms of mood and anxiety disorders. Althoughnot traditionally a prescriptive intervention, there are emerging efforts to have physicians and health organizations provide or prescribe healthy food options to patients.63 Given that depression and anxiety disorders cost the global economy $1 trillion dollars in lost produc- tivity each year, using nutrition augmentation strategies can be an easy and safe intervention that deserves more research.64 NONPHARMACOLOGIC INTERVENTIONS Light Therapy Light therapy (LT) involves the administration of bright light using a light box.29 In 2010, the American Psychi- atric Association Task Force on Complementary and Alternative Medicine in Major Depressive Disorder found evidence supporting LT monotherapy for depression, particularly seasonal depression.30 CAN- MAT guidelines recommend LT as a first-line monotherapy for seasonal affective disorder and a second-line monotherapy or adjunctive therapy for mild to moderate MDD.29 A 2019 meta-analysis of patients with seasonal affective disorder found that LT $ 1000 lux was superior to placebo.65 While another review found the evidence for the use of LT in seasonal affective disorder to be limited and inconclusive.66 Another 2019 meta-analysis of 397 patients found that LT mono- therapy was equivalent to antidepressant monotherapy and that combination of LT plus antidepressant therapy was superior to antidepressant monotherapy, even in patients with nonseasonal depression.67 In patients with bipolar depression, a meta-analysis found that LT was efficacious as monotherapy or as adjunctive therapy.68 Commonly reported side effects include eye strain, headache, agitation, nausea, and sedation, but otherwise LT is generally well tolerated.29 Patients with bipolar depression may be at risk for induction of mania.30 Caution should be taken with administering LT if the patient is taking photosensitizing drugs such as St. John’s wort, statins, diuretics, nonsteroidal anti- inflammatory drugs, and some antibiotics.30 Morning is generally thought to be the most efficacious time to administer light, but intensity and duration may vary 6 www.psychosomaticsjournal.org and can be adjusted rapidly based on the patient’s response.30 The standard treatment is 10,000 lux for 30 minutes every early morning for up to 6 weeks, with response usually in 1–3 weeks.29 Yoga Yoga is an ancient Indian spiritual practice that in- volves assuming postures, controlling breathing, and meditating.29 A 2015 meta-analysis found that yoga improved depressive symptoms but also found a low level of quality among RCTs and variability of yoga interventions.69 Despite the lower quality of evidence, CANMAT recommends yoga as a second-line adjunc- tive therapy in mild to moderate MDD, and a review by Asher et al.27 recommends yoga as a possibly effective ancillary treatment for depression.29 A 2018 meta-analysis found that yoga decreased anxiety symptoms in individuals with elevated levels of anxiety, but this effect went away when only including patients with a DSM-diagnosed anxiety disorder.70 Yoga is generally well tolerated, and adverse effects are related to the patient’s level of physical fitness.29 Injury may occur from excessive or incorrect yoga practice, and there may be a risk for meditation-induced mania or psychosis.29 Yoga interventions generally involve 2–4 sessions per week for 2–3 months.29 Exercise CANMAT recommends exercise as a first-line mono- therapy for mild to moderate MDD and as a second- line adjunctive therapy for moderate to severe MDD.29 Although studies have generally been positive, the benefit may be small. A 2014 review found that exercise was superior to placebo for reducing depressive symptoms, but the effect diminished when only high- quality studies were included.71 A 2017 meta-analysis by Krogh et al.72 examined 35 trials enrolling 2498 participants. Initially, they found a substantial antide- pressant effect of exercise intervention, but when excluding publications with higher risk of bias, they found no effect. Exercise was not shown to improve cognition and cognitive symptoms associated with depression.73 More recently, a 2019 review specifically examining aerobic exercise for MDD found a large antidepressant effect that remained, even when excluding trials with higher risk of bias.74 Data on adverse effects are limited, but musculoskeletal com- plaints have been reported.33,72 In terms of treatment, Psychosomatics -:-, - 2020 http://www.psychosomaticsjournal.org TABLE 1. Summary of Indications, Dosing, and Safety Concerns Therapy Indication Dosing Safety Other comments Ginkgo Dementia 240 mg/d p.o. for at least 4–6 wk Drug-drug interactions; serotonin syndrome; bleeding; stroke/TIA; arrhythmias Not recommended for healthy individuals with concerns about dementia later in life; avoid in combination with anticoagulants or before surgery Kava Kava Anxiety Up to 120 mg/d p.o. for no more than 8 wk Hepatotoxicity; dermatitis Monitor liver function tests, avoid in patients with liver disease Omega-3 Depression 1–2 g/d p.o. for 8–12 wk Bleeding (possibly not so common); mania Use with caution in people undergoing surgery and people with prostate cancer SAMe Depression 500–1600 mg/d p.o. in divided doses with meals for 6–12 wk 200–400 mg/d IV or IM for 2–8 wk Mania (particularly when given IV or IM) Gastrointestinal upset is a common, but mild side effect St. John’s Wort Depression 500–1800 mg/d p.o. for 6–8 wk Drug-drug interactions; serotonin syndrome; mania; photosensitivity Avoid intense sun exposure while taking Tryptophan/5-HTP Depression Tryptophan: 2–4 g/d for 6–8 wk 5-HTP: 200–300 mg/d in 2–4 doses each day Serotonin syndrome; Increased risk for lithium toxicity; eosinophilia-myalgia syndrome Current preparations generally considered safe Light therapy Depression, seasonal depression, bipolar depression 10,000 lux for 30 min in the early morning for 6 wk Mania Use with caution in patients taking photosensitizing medications Yoga Depression, anxiety 2–4 sessions per week for 2–3 months Injury; meditation-induced mania or psychosis Some patients with depression may find the discipline too rigorous Exercise Depression 30 min of moderate intensity 3 times per week for at least 9 wk Injury Some patients with depression may find the discipline too rigorous 5-HTP = 5-hydroxy tryptophan; IM = intramuscular; IV = intravenous; SAMe = S-adenosyl-L-methionine; TIA = transient ischemic attack. B erm an et al. P sychosom atics - :- , - 2020 w w w .psychosom aticsjournal.org 7 Licenciado para - Raphael Pacheco de Miranda - 02312325780 - Protegido por Eduzz.com http://www.psychosomaticsjournal.org Medications in Psychiatry Licenciado para - R aphael P acheco de M iranda - 02312325780 - P rotegido por E duzz.com CANMAT guidelines recommend at least 30 minutes of moderate intensity exercise 3 times a week for at least 9 weeks, with adjustments based on the fitness of the individual.29 CONCLUSION CAM therapies are commonly used in America, and physicians can benefit from understanding the psychi- atric indications and safety of these therapies. There is growing evidence supporting the efficacy of certain therapies in treating mental health conditions, and this may benefit patients who prefer treatments that are alternative to or complementary with registered thera- pies. In this review, we have focused primarily on treatments that have more rigorous data to support them, particularly in the form of meta-analyses. How- ever, it should be noted that when studies are grouped in a meta-analysis, they may provide generalizable data but lose specificity to clinical subpopulations; they are also less informative of individual responses. The studies are variable in quality, with one major limita- tion being small sample sizes, given that financial re- sources available to investigators in the field of CAM are modest compared with those of large pharmaceu- tical companies that can fund large, adequately pow- ered studies. Larger andmore rigorous studies on well- defined clinical populations are needed to clarify the place of CAM in the psychiatric armamentarium. Nonetheless, many clinicians and clinical scientists would likely state that their experience of treating pa- tients with CAM supports their use in depression and 8 www.psychosomaticsjournal.org anxiety. Clinicians therefore need to balance recom- mendations from the literature with their own real-world observations, with the understanding that individualization of treatment may ultimately be the key to better outcomes. With this in mind, we have summarized on Table 1 the treatments outlined here, their putative indications, doses, and safety consider- ations. The psychiatrist considering recommending these therapies, or seeking to advise a patient already using any of them, can reference the table as a frame- work for discussion and informing the patient. Finally, physicians should routinely inquire about the use of CAM, especially in light of side effects, adverse events, and medication interactions. These treatments should be ideally administered under the guidance of a trained medical professional. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosure: Sarah Berman and Uma Naidoo have no disclosures. David Mischoulon has received research support from Nordic Naturals. He has provided unpaid consulting for Pharmavite LLC and Gnosis USA, Inc. He has received honoraria for speaking from the Mas- sachusetts General Hospital Psychiatry Academy, Blackmores, Harvard Blog, and PeerPoint Medical Education Institute, LLC. He has received royalties from Lippincott Williams & Wilkins for published book “Natural Medications for Psychiatric Disorders: Considering the Alternatives.” References 1. Wieland LS, Manheimer E, Berman BM: Development and classification of an operational definition of complementary and alternative medicine for the Cochrane collaboration. Altern Ther Health Med 2011; 17:50–59 2. 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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref71 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref71 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref73 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref73 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref73 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref74 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref74 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref74 http://refhub.elsevier.com/S0033-3182(20)30123-7/sref74 http://www.psychosomaticsjournal.org Complementary Medicine and Natural Medications in Psychiatry: A Guide for the Consultation-Liaison Psychiatrist Introduction Natural Medications Ginkgo (Ginkgo biloba, EGb) Kava Kava (Piper methysticum) Omega-3 Fatty Acids (Fish Oil, Eicosapentaenoic Acid, Docosahexaenoic Acid) S-Adenosyl-L-Methionine St. John's Wort (Hypericum perforatum) Tryptophan/5-Hydroxytryptophan Nutritional Psychiatry Nonpharmacologic Interventions Light Therapy Yoga Exercise Conclusion References
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