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Psychosomatics 2020:-:-–- ª 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.
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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
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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
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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
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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
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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
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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.
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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
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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
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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
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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,
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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.
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aticsjournal.org
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http://www.psychosomaticsjournal.org
Medications in Psychiatry
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aphael P
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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. Clarke TC, Black LI, Stussman BJ, Barnes PM, Nahin RL:
Trends in the use of complementary health approaches
among adults: United States, 2002-2012. Natl Health Stat
Report 2015:1–16
3. Black LI, Clarke TC, Barnes PM, Stussman BJ, Nahin RL:
Use of complementary health approaches among children
aged 4-17 years in the United States: National Health Inter-
view Survey, 2007-2012. Natl Health Stat Rep 2015:1–19
4. Sarris J, Logan AC, Akbaraly TN, et al: Nutritional medicine as
mainstream in psychiatry. Lancet Psychiatry 2015; 2:271–274
5. Wang C, Preisser J, Chung Y, Li K: Complementary and
alternative medicine use among children with mental health
issues: results from the National Health Interview Survey.
BMC Complement Altern Med 2018; 18:241
6. Jou J, Johnson PJ: Nondisclosure of complementary and
alternative medicine use to primary care physicians: findings
from the 2012 National Health Interview Survey. JAMA
Intern Med 2016; 176:545–546
7. Mei N, Guo X, Ren Z, Kobayashi D, Wada K, Guo L:
Review of Ginkgo biloba-induced toxicity, from experimental
studies to human case reports. J Environ Sci Health C En-
viron Carcinog Ecotoxicol Rev 2017; 35:1–28
8. Solomon PR, Adams F, Silver A, Zimmer J, DeVeaux R:
Ginkgo for memory enhancement: a randomized controlled
trial. JAMA 2002; 288:835–840
9. Snitz BE, O’Meara ES, Carlson MC, et al: Ginkgo biloba for
preventing cognitive decline in older adults: a randomized
trial. JAMA 2009; 302:2663–2670
10. Vellas B, Coley N, Ousset P-J, et al: Long-term use of
standardised Ginkgo biloba extract for the prevention of
Psychosomatics -:-, - 2020
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref1
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref1
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref1
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref1
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref2
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref2
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref2
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref2
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref3
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref3
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref3
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref3
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref4
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref4
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref5
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref5
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref5
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref5
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref6
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref6
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref6
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref6
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref7
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref7
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref7
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref7
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref8
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref8
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref8
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref9
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref9
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref9
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref10
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref10
http://www.psychosomaticsjournal.org
Berman et al.
Licenciado para - R
aphael P
acheco de M
iranda - 02312325780 - P
rotegido por E
duzz.com
Alzheimer’s disease (GuidAge): a randomised placebo-
controlled trial. Lancet Neurol 2012; 11:851–859
11. Birks J, Evans JG: Ginkgo biloba for cognitive impairment
and dementia. Cochrane Database Syst Rev 2009:CD003120
12. Herrschaft H, Nacu A, Likhachev S, Sholomov I, Hoerr R,
Schlaefke S: Ginkgo biloba extract EGb 761® in dementia
with neuropsychiatric features: a randomised, placebo-
controlled trial to confirm the efficacy and safety of a daily
dose of 240 mg. J Psychiatr Res 2012; 46:716–723
13. Ihl R, Bachinskaya N, Korczyn AD, et al: Efficacy and safety
of a once-daily formulation of Ginkgo biloba extract
EGb 761 in dementia with neuropsychiatric features: a ran-
domized controlled trial. Int J Geriatr Psychiatry 2011;
26:1186–1194
14. Kandiah N, Ong PA, Yuda T, et al: Treatment of dementia
and mild cognitive impairment with or without cerebrovas-
cular disease: expert consensus on the use of Ginkgo biloba
extract, EGb 761®. CNS Neurosci Ther 2019; 25:288–298
15. Yang G, Wang Y, Sun J, Zhang K, Liu J: Ginkgo biloba for
mild cognitive impairment and Alzheimer’s disease: a sys-
tematic review and meta-analysis of randomized controlled
trials. Curr Top Med Chem 2016; 16:520–528
16. Ahlemeyer B, Krieglstein J: Neuroprotective effects of
Ginkgo biloba extract. Cell Mol Life Sci 2003; 60:1779–1792
17. Diamond BJ, Bailey MR: Ginkgo biloba: indications,
mechanisms, and safety. Psychiatr Clin North Am 2013;
36:73–83
18. O’Brien JT, Holmes C, Jones M, et al: Clinical practice with
anti-dementia drugs: a revised (third) consensus statement
from the British Association for Psychopharmacology.
J Psychopharmacol 2017; 31:147–168
19. Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN:
Effects of Ginkgo biloba in dementia: systematic review and
meta-analysis. BMC Geriatr 2010; 10:14
20. Sarris J: Herbal medicines in the treatment of psychiatric
disorders: 10-year updated review. Phytother Res 2018;
32:1147–1162
21. Smith K, Leiras C: The effectiveness and safety of Kava kava
for treating anxiety symptoms: a systematic review and
analysis of randomized clinical trials. Complement Ther Clin
Pract 2018; 33:107–117
22. White CM: The pharmacology, pharmacokinetics, efficacy,
and adverse events associated with kava. J Clin Pharmacol
2018; 58:1396–1405
23. Witte S, Loew D, Gaus W: Meta-analysis of the efficacy of
the acetonicKava-kava extract WS1490 in patients with non-
psychotic anxiety disorders. Phytother Res 2005; 19:183–188
24. Ooi SL, Henderson P, Pak SC: Kava for generalized anxiety
disorder: a review of current evidence. J Altern Complement
Med 2018; 24:770–780
25. Sarris J, Stough C, Bousman CA, et al: Kava in the treatment
of generalized anxiety disorder: a double-blind, randomized,
placebo-controlled study. J Clin Psychopharmacol 2013;
33:643–648
26. Teschke R, Sarris J, Lebot V: Contaminant hepatotoxins as
culprits for kava hepatotoxicity–fact or fiction? Phytother
Res 2013; 27:472–474
Psychosomatics -:-, - 2020
27. Asher GN, Gerkin J, Gaynes BN: Complementary therapies
for mental health disorders. Med Clin North Am 2017;
101:847–864
28. Schefft C, Kilarski LL, Bschor T, Köhler S: Efficacy of
adding nutritional supplements in unipolar depression: a
systematic review and meta-analysis. Eur Neuro-
psychopharmacol 2017; 27:1090–1109
29. Ravindran AV, Balneaves LG, Faulkner G, et al: Canadian
Network for Mood and Anxiety Treatments (CANMAT)
2016 clinical guidelines for the management of adults with
major depressive disorder: section 5. Complementary and
alternative medicine treatments. Can J Psychiatry 2016;
61:576–587
30. Freeman MP, Fava M, Lake J, Trivedi MH, Wisner KL,
Mischoulon D: Complementary and alternative medicine in
major depressive disorder: the American Psychiatric Associ-
ation Task Force report. J Clin Psychiatry 2010; 71:669–681
31. U.S. Food & Drug Administration: FDA approves use of drug
to reduce risk of cardiovascular events in certain adult patient
groups. Available from: https://www.fda.gov/news-events/
press-announcements/fda-approves-use-drug-reduce-risk-
cardiovascular-events-certain-adult-patient-groups; 2019
32. Grosso G, Micek A, Marventano S, et al: Dietary n-3 PUFA,
fish consumption and depression: a systematic review and
meta-analysis of observational studies. J Affect Disord 2016;
205:269–281
33. Asher GN, Gartlehner G, Gaynes BN, et al: Comparative
benefits and harms of complementary and alternative medi-
cine therapies for initial treatment of major depressive dis-
order: systematic review and meta-analysis. J Altern
Complement Med 2017; 23:907–919
34. Sarris J, Murphy J, Mischoulon D, et al: Adjunctive nutra-
ceuticals for depression: a systematic review and meta-ana-
lyses. Am J Psychiatry 2016; 173:575–587
35. Hallahan B, Ryan T, Hibbeln JR, et al: Efficacy of omega-3
highly unsaturated fatty acids in the treatment of depression.
Br J Psychiatry 2016; 209:192–201
36. Mocking RJT, Harmsen I, Assies J, Koeter MWJ, Ruhé HG,
Schene AH: Meta-analysis and meta-regression of omega-3
polyunsaturated fatty acid supplementation for major
depressive disorder. Transl Psychiatry 2016; 6:e756
37. Deane KHO, Jimoh OF, Biswas P, et al: Omega-3 and
polyunsaturated fat for prevention of depression and anxiety
symptoms: systematic review and meta-analysis of rando-
mised trials. Br J Psychiatry 2019:1–8
38. Appleton KM, Sallis HM, Perry R, Ness AR, Churchill R:
Omega-3 fatty acids for depression in adults. Cochrane
Database Syst Rev 2015:CD004692
39. Patrick RP, Ames BN: Vitamin D and the omega-3 fatty
acids control serotonin synthesis and action, part 2: relevance
for ADHD, bipolar disorder, schizophrenia, and impulsive
behavior. FASEB J 2015; 29:2207–2222
40. Mischoulon D, Freeman MP: Omega-3 fatty acids in psy-
chiatry. Psychiatr Clin North Am 2013; 36:15–23
41. Begtrup KM, Krag AE, Hvas AM: No impact of fish oil
supplements on bleeding risk: a systematic review. Dan Med
J 2017; 64:A5366
www.psychosomaticsjournal.org 9
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref10
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref10
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref11
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref11
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref12
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref12
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref12
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref12
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref12
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref13
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref13
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref13
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref13
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref13
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref14
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref14
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref14
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref14
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref15
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref15
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref15
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref15
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref16
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref16
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref17
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref17
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref17
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref18
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref18
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref18
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref18
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref19
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref19
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref19
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref20
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref20
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref20
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref21
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref21
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref21
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref21
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref22
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref22
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref22
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref23
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref23
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref23
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref24
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref24
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref24
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref25
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref25
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref25
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref25
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref26
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref26
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref26
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref27
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref27
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref27
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref28
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref28
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref28
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref28
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref29
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref29
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref29
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref29
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref29
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref29
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref30
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref30
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref30
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref30
https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups
https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups
https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groupshttp://refhub.elsevier.com/S0033-3182(20)30123-7/sref32
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref32
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref32
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref32
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref33
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref33
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref33
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref33
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref33
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref34
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref34
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref34
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref35
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref35
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref35
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref36
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref36
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref36
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref36
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref37
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref37
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref37
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref37
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref38
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref38
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref38
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref39
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref39
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref39
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref39
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref40
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref40
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref41
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref41
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref41
http://www.psychosomaticsjournal.org
Medications in Psychiatry
Licenciado para - R
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duzz.com
42. Liao Y, Xie B, Zhang H, et al: Efficacy of omega-3 PUFAs in
depression: a meta-analysis. Transl Psychiatry 2019; 9:190
43. Papakostas GI, Cassiello CF, Iovieno N: Folates and S-
adenosylmethionine for major depressive disorder. Can J
Psychiatry 2012; 57:406–413
44. Galizia I, Oldani L, Macritchie K, et al: S-adenosyl methi-
onine (SAMe) for depression in adults. Cochrane Database
Syst Rev 2016; 10:CD011286
45. Sarris J, Byrne GJ, Bousman C, et al: Adjunctive S-adeno-
sylmethionine (SAMe) in treating non-remittent major depres-
sive disorder: an 8-week double-blind, randomized, controlled
trial. Eur Neuropsychopharmacol 2018; 28:1126–1136
46. Sarris J, Price LH, Carpenter LL, et al: Is S-adenosyl
methionine (SAMe) for depression only effective in males? A
re-analysis of data from a randomized clinical trial. Phar-
macopsychiatry 2015; 48:141–144
47. Dome P, Tombor L, Lazary J, Gonda X, Rihmer Z: Natural
health products, dietary minerals and over-the-counter med-
ications as add-on therapies to antidepressants in the treat-
ment of major depressive disorder: a review. Brain Res Bull
2019; 146:51–78
48. Gao J, Cahill CM, Huang X, et al: S-adenosyl methionine
and transmethylation pathways in neuropsychiatric diseases
throughout life. Neurotherapeutics 2018; 15:156–175
49. Ng QX, Venkatanarayanan N, Ho CY: Clinical use of
Hypericum perforatum (St John’s wort) in depression: a
meta-analysis. J Affect Disord 2017; 210:211–221
50. Apaydin EA, Maher AR, Shanman R, et al: A systematic
review of St. John’s wort for major depressive disorder. Syst
Rev 2016; 5:148
51. Shelton RC, Keller MB, Gelenberg A, et al: Effectiveness of
St John’s wort in major depression: a randomized controlled
trial. JAMA 2001; 285:1978–1986
52. Sarris J: St. John’s wort for the treatment of psychiatric
disorders. Psychiatr Clin North Am 2013; 36:65–72
53. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ: Pharmacoki-
netic interactions of drugs with St John’s wort.
J Psychopharmacol 2004; 18:262–276
54. Iovieno N, Dalton ED, Fava M, Mischoulon D: Second-tier
natural antidepressants: review and critique. J Affect Disord
2011; 130:343–357
55. Jacobsen JPR, Krystal AD, Krishnan KRR, Caron MG:
Adjunctive 5-hydroxytryptophan slow-release for treatment-
resistant depression: clinical and preclinical rationale.
Trends Pharmacol Sci 2016; 37:933–944
56. Jangid P, Malik P, Singh P, Sharma M, Gulia AK:
Comparative study of efficacy of l-5-hydroxytryptophan and
fluoxetine in patients presenting with first depressive episode.
Asian J Psychiatr 2013; 6:29–34
57. Sarris J, Byrne GJ, Stough C, et al: Nutraceuticals for major
depressive disorder- more is not merrier: an 8-week double-
blind, randomised, controlled trial. J Affect Disord 2019;
245:1007–1015
58. van Zoonen K, Buntrock C, Ebert DD, et al: Preventing the
onset of major depressive disorder: a meta-analytic review of
psychological interventions. Int J Epidemiol 2014; 43:318–
329
10 www.psychosomaticsjournal.org
59. Molendijk M, Molero P, Ortuño Sánchez-Pedreño F, Van
der Does W, Angel Martínez-González M: Diet quality and
depression risk: a systematic review and dose-response meta-
analysis of prospective studies. J Affect Disord 2018;
226:346–354
60. Firth J, Siddiqi N, Koyanagi A, et al: The Lancet Psychiatry
Commission: a blueprint for protecting physical health in
people with mental illness. Lancet Psychiatry 2019; 6:675–
712
61. Psaltopoulou T, Sergentanis TN, Panagiotakos DB,
Sergentanis IN, Kosti R, Scarmeas N: Mediterranean diet,
stroke, cognitive impairment, and depression: a meta-anal-
ysis. Ann Neurol 2013; 74:580–591
62. Parletta N, Zarnowiecki D, Cho J, et al: A Mediterranean-
style dietary intervention supplemented with fish oil improves
diet quality and mental health in people with depression: a
randomized controlled trial (HELFIMED). Nutr Neurosci
2019; 22:474–487
63. Swartz H: Produce Rx programs for diet-based chronic dis-
ease prevention. AMA J Ethics 2018; 20:960–973
64. Chisholm D, Sweeny K, Sheehan P, et al: Scaling-up treat-
ment of depression and anxiety: a global return on invest-
ment analysis. Lancet Psychiatry 2016; 3:415–424
65. Pjrek E, Friedrich M-E, Cambioli L, et al: The efficacy of
light therapy in the treatment of seasonal affective disorder: a
meta-analysis of randomized controlled trials. Psychother
Psychosom 2020; 89:17–24
66. Nussbaumer-Streit B, Forneris CA, Morgan LC, et al: Light
therapy for preventing seasonal affective disorder. Cochrane
Database Syst Rev 2019; 3:CD011269
67. Geoffroy PA, Schroder CM, Reynaud E, Bourgin P: Efficacy
of light therapy versus antidepressant drugs, and of the
combination versus monotherapy, in major depressive epi-
sodes: a systematic review and meta-analysis. Sleep Med Rev
2019; 48:101213
68. Tseng PT, Chen YW, Tu KY, et al: Light therapy in the
treatment of patients with bipolar depression: a meta-analytic
study. Eur Neuropsychopharmacol 2016; 26:1037–1047
69. Cramer H, Lauche R, Langhorst J, Dobos G: Yoga for
depression: a systematic review and meta-analysis. Depress
Anxiety 2013; 30:1068–1083
70. Cramer H, Lauche R, Anheyer D, et al: Yoga for anxiety: a
systematic review and meta-analysis of randomized
controlled trials. Depress Anxiety 2018; 35:830–843
71. Cooney G, Dwan K, Mead G: Exercise for depression.
JAMA 2014; 311:2432–2433
72. Krogh J, Hjorthøj C, Speyer H, Gluud C, Nordentoft M:
Exercise for patients with major depression: a systematic re-
view with meta-analysis and trial sequential analysis. BMJ
Open 2017; 7:e014820
73. Sun M, Lanctot K, Herrmann N, Gallagher D: Exercise
for cognitive symptoms in depression: a systematic review
of interventional studies. Can J Psychiatry 2018; 63:115–128
74. Morres ID, Hatzigeorgiadis A, Stathi A, et al: Aerobic ex-
ercise for adult patients with major depressive disorder in
mental health services: a systematic review and
meta-analysis. Depress Anxiety 2019; 36:39–53Psychosomatics -:-, - 2020
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref42
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref42
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref43
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref43
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref43
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref44
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref44
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref44
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref45
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref45
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref45
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref45
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref46
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref46
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref46
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref46
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref47
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref47
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref47
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref47
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref48
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref48
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref48
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref49
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref49
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref49
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref50
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref50
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref50
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref51
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref54
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref54
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref55
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref55
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref55
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref55
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref56
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref56
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref56
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref56
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref57
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref57
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref57
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref57
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref59
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref59
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref59
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref60
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref60
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref60
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref60
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref61
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref61
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref61
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref61
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref62
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref62
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref64
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref64
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref64
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref65
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref65
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref65
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref65
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref66
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref66
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref66
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref67
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref67
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref67
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref67
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref67
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref68
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref68
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref68
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref69
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref69
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref69
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref70
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref71
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72
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http://refhub.elsevier.com/S0033-3182(20)30123-7/sref72
http://refhub.elsevier.com/S0033-3182(20)30123-7/sref73
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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