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Herbal and dietary supplements for treatment of anxiety disorders


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Use of complementary and alternative medicine has increased over the past decade. A variety of studies have suggested that this use is greater in persons with symptoms or diagnoses of anxiety and depression. Data support the effectiveness of some popular herbal remedies and dietary supplements; in some of these products, particularly kava, the potential for benefit seems greater than that for harm with short-term use in patients with mild to moderate anxiety. Inositol has been found to have modest effects in patients with panic disorder or obsessive-compulsive disorder. Physicians should not encourage the use of St. John's wort, valerian, Sympathyl, or passionflower for the treatment of anxiety based on small or inconsistent effects in small studies. Although the evidence varies depending on the supplement and the anxiety disorder, physicians can collaborate with patients in developing dietary supplement strategies that minimize risks and maximize benefits.
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Herbal and Dietary Supplements for
Treatment of Anxiety Disorders
East Carolina University, Greenville, North Carolina
se of complementary and alter-
native medicine in all of its
varieties, such as herbal rem-
edies and dietary supplements,
increased from 34 percent of the overall U.S.
population in 1990 to 42 percent in 1997.
Use appears to be twice as great in persons
reporting anxiety and depression than in
those reporting any other problem, except
for back and neck pain.
Based on results of
two large-scale community surveys,
tigators have noted an association between
both panic disorder and major depression
and the use of complementary and alterna-
tive medicine.
Currently, the preferred treatment for anx-
iety disorders is cognitive behavior therapy
and pharmacologic agents. Beta blockers or
benzodiazepines are used for time-limited
and predictable anxiety disorders, whereas
selective serotonin reuptake inhibitors
(SSRIs), selective serotonin-norepinephrine
reuptake inhibitors, tricyclic antidepres-
sants, buspirone (Buspar), or monoamine
oxidase inhibitors are preferred for chronic
or recurrent anxiety disorders.
In recent years, studies using herbal rem-
edies and supplements to treat mild to mod-
erate anxiety disorders have emerged. It is
important for physicians to recognize that
supplements offer both benefits and risks.
By doing so, they can avoid an overly dismis-
sive attitude that discourages patients from
disclosing their supplement use. At the same
time, understanding the limits of avail-
able evidence allows physicians to collabo-
rate with interested patients in developing
dietary supplement strategies that minimize
risks and maximize benefits.
In this article, the supplements purported
to ameliorate anxiety disorders are divided
into three groups: herbal supplements,
nutritional supplements, and neurotrans-
mitter and hormonal precursors. These divi-
sions are somewhat arbitrary in that all of
the products are taken orally, are available
over the counter, are marketed with a vari-
ety of health claims on the Internet, and are
justified by their purported ultimate effects
on the neurotransmitter systems that medi-
ate worry, stress, or fatigue symptoms in
patients with anxiety disorders.
Information on supplements that claim
to be useful or commonly used for anxiety
disorders was obtained from several Inter-
net sites, particularly http://www.revolution, http://www.
treatment/alternative_treatment.asp, and
http:/ Medline
via Ovid was used to search for clinical
trials, guidelines, and meta-analyses that
Use of complementary and alternative medicine has increased over the past decade. A variety of
studies have suggested that this use is greater in persons with symptoms or diagnoses of anxiety and
depression. Data support the effectiveness of some popular herbal remedies and dietary supple-
ments; in some of these products, particularly kava, the potential for benefit seems greater than that
for harm with short-term use in patients with mild to moderate anxiety. Inositol has been found
to have modest effects in patients with panic disorder or obsessive-compulsive disorder. Physicians
should not encourage the use of St. Johns wort, valerian, Sympathyl, or passionflower for the treat-
ment of anxiety based on small or inconsistent effects in small studies. Although the evidence varies
depending on the supplement and the anxiety disorder, physicians can collaborate with patients
in developing dietary supplement strategies that minimize risks and maximize benefits. (Am Fam
Physician 2007;76:549-56. Copyright © 2007 American Academy of Family Physicians.)
Downloaded from the American Family Physician Web site at Copyright © 2007 American Academy of Family Physicians. For the private, noncommercial
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550 American Family Physician Volume 76, Number 4
August 15, 2007
Herbs for Anxiety
tested or asserted the effectiveness of these
preparations in the treatment of patients
with diagnosed anxiety disorders. Table 1
includes suggested supplements that have
some evidence of effectiveness for treating
anxiety. Only therapies with evidence of
effectiveness are discussed in this review.
Patients often justify the use of certain
preparations on the basis of irrelevant or
misleading evidence; to help physicians
Clinical recommendation
rating References Comments
Short-term use of kava is recommended for patients with
mild to moderate anxiety disorders who are not using
alcohol or taking other medicines metabolized by the
liver, but who wish to use natural” remedies.
A 4, 5 Cochrane systematic review of seven RCTs
(n = 380), with findings supported by five
lower-quality trials (n = 320); side effects
were rare and mild; same results with only
extract WS1490 trials
Use of inositol in a dosage of 12 to 18 g per day is a
treatment option for panic disorder.
B 24, 25 Effectiveness similar to SSRI and better than
placebo for reducing intensity and frequency
of panic attacks; side-effect profile
comparable to SSRI; supported by two RCTs,
although both were small
Inositol, 12 to 18 g per day, may be used to treat
obsessive-compulsive disorder but not in combination
with SSRIs.
B 26, 27 In trials of patients with treatment-resistant
OCD, inositol by itself was better than
placebo in reducing OCD symptoms
but not
in reducing anxiety scale scores; when added
to SSRIs, inositol had no additional effect
Physicians should not encourage the use of St. John’s
wort, valerian, Sympathyl, or passionflower for anxiety
based on small or inconsistent effects in small studies.
Side-effect profiles are benign.
B 16-23 Small, unreplicated trials with design flaws
suggest some limited effectiveness
All other nutritional supplements have no research evidence
suggesting a positive effect on anxiety disorders.
Physicians should recommend other treatments.
C No evidence beyond testimonials, effects
on nonclinical groups, or hypothetical
mechanisms of action
RCT = randomized controlled trial; SSRI = selective serotonin reuptake inhibitor; OCD = obsessive-compulsive disorder.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 483 or
Table 1. Supplements with Clinical Trial Evidence of Effectiveness or
Noneffectiveness for Treating Anxiety
Type of evidence Herbal supplements Nutritional supplements
hormonal precursors
Effectiveness based on meta-
analysis or multiple RCTs
Effectiveness based on
a single double-blind,
placebo-controlled RCT
St. John’s wort (for somatoform
disorders), sympathyl (California poppy,
hawthorn, elemental magnesium)
Inositol, 18 g (one RCT for
panic disorder and one RCT
for OCD)
(serotonin precursor;
for panic disorder)
Weak effectiveness based
on clinical/open trials
Passionflower, St. John’s wort (for GAD),
Clinical trials demonstrating
Cannabis Omega-3 fatty acids (as adjunct
for treatment-resistant OCD)
NOTE: The preparations are listed in order from the most evidence of effectiveness to the least evidence.
RCT = randomized controlled trial; OCD = obsessive-compulsive disorder; GAD = generalized anxiety disorder.
August 15, 2007
Volume 76, Number 4 American Family Physician 551
Herbs for Anxiety
recognize such preparations, those supple-
ments with no clinical evidence of effective-
ness in reducing anxiety are presented in
Table 2. Clearly, the vast majority of supple-
ments with purported anxiolytic effects have
no evidence of clinical benefit.
Herbal Supplements
There is substantial evidence that kava has
a positive effect on the symptoms of anxiety
disorders. Table 3 summarizes the evidence
on the effectiveness and safety of kava in
patients with anxiety disorders.
Kava dramatically inhibits the cytochrome
P450 enzyme used by the liver to metabo-
lize many medications, potentially altering
the potency of these other medications.
Thus, it is important to be aware of the risk
of drug interactions with kava. Other side
effects reported with long-term use include
a reversible skin rash or lesion and a yellow
tint to the skin, but these reports have not
been routine. Despite the absence of long-
term data on safety and effectiveness,
evidence shows that short-term use (i.e., up
to 24 weeks) can lead to small improvements
in generalized anxiety,
and that short-term
risks do not outweigh the benefits.
For patients with mild to moderate anxiety
who wish to use naturalremedies and are
not using alcohol or taking other medica-
tions that are metabolized by the liver, kava
appears to be acceptable for short-term use.
St. John’s wort is a popular supplement for
treating depression but is much less popular
for treating anxiety disorders. Studies specifi-
cally testing the effects of St. John’s wort on
patients with anxiety are extremely limited.
Table 4 summarizes the evidence for the
effectiveness and safety of St. John’s wort in
the treatment of anxiety disorders.
The evidence of positive effects of St.
John’s wort on anxiety disorders is weak. No
placebo-controlled, randomized, double-
blind trials have shown St. Johns wort to
be effective in treating generalized anxi-
ety disorder, post-traumatic stress disorder,
obsessive-compulsive disorder (OCD), or
phobias. The only effective trial
involved patients with somato-
form disorder, although the
relationship between somato-
form disorder and anxiety is
complex. Much stronger evi-
dence is needed before St.
Johns wort should be considered a treat-
ment option for patients with diagnosable
anxiety disorders.
A single French study exists of a combination
product called Sympathyl,
which contains 20
mg California poppy, 75 mg hawthorn, and 75
mg elemental magnesium. According to the
study, Sympathyl had a very small but posi-
tive effect on anxiety. No clinical trials suggest
that any of the individual components reduce
anxiety in patients with anxiety disorders.
Although valerian is often cited as hav-
ing anxiolytic effects and has been used
for centuries by herbalists/physicians to
treat nervousness, there are only two small
trials involving valerian, neither of which
produced clear indications of effectiveness
(Table 4
). Thus, at the present time, there
Table 2. Supplements with No Clinical Trial Evidence
of Effectiveness in Anxiety Disorders
Herbal supplements
Ashwagandha (Withania somnifera); Bach flower essences; bacopa; berocca;
borage juice (starflower); bugleweed (Lycopus virginicus); catnip; chamomile;
damiana; fennel; feverfew; ginkgo; ginseng; golden root (Rhodiola
rosea); gotu kola; hops; kanna; lemon balm; lemongrass leaves; licorice;
meadowsweet; motherwort; mullein (Verbascum sinuatum); mulungu;
noni (Morinda citrifolia); peppermint; pine bark extract; reishi (Ganoderma
lucidum); Relora (magnolia/phellodendron); schisandra; scullcup (skullcap);
verbena (blue vervain)
Nutritional supplements
Adrenal extracts; carbohydrate-rich diet; garum armoricum (great bluefish);
ginger; L-theanine (green tea); macrobiotic diet; milk peptides (New Life
Tryptozen); oats; perilla oil (perilla frutescens); vitamins B
, B
, B
, and C
Neurotransmitter and hormonal precursors
Amino acids (L-phenylalanine/phenylalanine [norepinephrine precursor],
L-arginine, L-lysine, L-glutamine, L-leucine); melatonin; pregnenolone;
phytoestrogens (soy or Mexican yam); tyrosine (norepinephrine precursor);
SAMe (S-adenosyl-L-methionine)
Although valerian has been
widely used to treat anxi
ety, there is no evidence of
an anxiolytic effect.
552 American Family Physician Volume 76, Number 4
August 15, 2007
Herbs for Anxiety
is no clinical evidence of an anxiolytic effect
of valerian when compared with placebo in
patients with anxiety disorder.
A single randomized double-blind trial com-
pared 45 drops of passionflower tincture per
day to 30 mg per day of oxazepam (Serax;
brand no longer available in the United
States) for 30 days.
Investigators noted a
marked reduction in anxiety score in both
groups, but without a placebo group it was
unclear whether other aspects of the milieu
could have caused the effects.
Nutritional Supplements
Despite the number of nutritional supple-
ments purported on the Internet to treat
anxiety, only inositol, part of the vitamin B
complex (B8) and an intracellular second mes-
senger, has evidence suggesting superiority
to placebo and even comparability with the
SSRI fluvoxamine (Luvox; brand no lon-
ger available in the United States). Table 5
summarizes the evidence supporting the
effectiveness and safety of inositol in manag-
ing anxiety disorders.
Inositol appears to have a positive effect
on patients with panic disorder; however,
its effect on patients with OCD is less clear.
Physicians should inform patients that the
limited data that exist to date suggest partial
responses with a side-effect profile that may
be comparable with that of SSRIs.
Neurotransmitter or Hormonal
The anxiolytic neurotransmitter or hor-
monal precursors with some evidence of
effectiveness are shown in Table 1. The
vast majority of neurotransmitter or hor-
monal precursors that claim to be useful
Table 3. Evidence Regarding the Effectiveness and Safety of Kava in Anxiety Disorders
Design Description Comments
on GAD
A Cochrane systematic review identified 12 RCTs of
effects of kava on patients with GAD
; the meta-analysis
included seven trials that met quality criteria (n = 380);
kava significantly reduced Hamilton Anxiety Scale scores,
although the weighted mean difference between kava
and placebo was only 3.9 scale points; the other five trials
(n = 320) showed similar tendencies; a replication meta-
analysis involving only those RCTs that used extract WS1490
replicated and extended these results
Kava was consistently better than placebo in
producing small reductions in anxiety symptoms;
side effects noticed across all studies were “mild,
transient, and infrequent
; the authors concluded
that kava taken for one to 24 weeks was safe and
mildly effective; the replication
allowed more
comparisons between patient subgroups and
suggested most improvement effects in women
and patients younger than 53 years
RCTs on GAD Recent small RCTs involving patients with GAD (n = 64)
showed no significant effect of kava,
with treatments
typically lasting four weeks
Trial durations were short, and sample size was small;
although studies of eight weeks’ duration
shown effectiveness, a 25-week study
that therapeutic effects started in the eighth week
RCT on safety Recent examinations of adverse event reports with kava
improved understanding of the pharmacologic substances
in kava
show that its safety compares favorably with FDA-
approved treatments for anxiety disorders
Researchers concluded that liver toxicity is rare and
idiosyncratic, with the majority of reported cases
resulting from the combination of kava with other
hepato-active agents; the benefits of kava seem
to outweigh its risks
Case reports
on safety
Cases of liver toxicity have been reported, some requiring organ
transplants; kava preparations withdrawn from the market in
many countries; the FDA issued an advisory
; later, research
suggested that nonstandard inclusion of the kava plant’s bark
in kava preparations increased toxicity level
Unclear if dosing, preexisting liver damage, or toxic
combinations with other hepato-active agents
were causative
GAD = generalized anxiety disorder; RCT = randomized controlled trial; FDA = U.S. Food and Drug Administration.
Information from references 4 through 12.
August 15, 2007
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Herbs for Anxiety
Table 4. Evidence Regarding the Effectiveness and Safety of St. John’s Wort, Valerian, Sympathyl,
and Passionflower in Anxiety Disorders
Design Description Comments
RCT with St. John’s wort in
Compared 30 patients with OCD taking LI 160 extract (range:
300 to 1,800 mg) and 30 patients with OCD taking placebo
for 12 weeks
; St. Johns wort had no effect on reducing Yale-
Brown Obsessive-Compulsive Scale total or subscale scores
Agitation side effect more common
with St. John’s wort
Open, uncontrolled study of
St. John’s wort in OCD
Significant reductions in the Yale-Brown Obsessive-
Compulsive Scale score in 12 patients with OCD starting
one week into the study and continuing throughout the
12-week trial
; the compound used was a 450-mg,
extended-release formulation of 0.3% Hypericum taken
two times a week
The small number of patients and
lack of comparison to placebo
make this evidence weak; few side
effects reported
RCT with St. John’s wort in
social phobias
Compared flexible doses of LI 160 extract (range: 300 to
1,800 mg twice a day) and placebo in 40 patients with social
; St. John’s wort had no effect in reducing anxiety
Side effects no worse than placebo
RCT with St. John’s wort in
somatoform disorders
St. John’s wort was used to treat somatoform disorders
using reductions in the Hamilton Anxiety Scale somatic
anxiety subscale score as the primary outcome measure
after patients with significant depressive symptoms were
excluded, 150 patients were randomized to St. John’s wort
or placebo; dosage of the LI 160 extract was 300 mg
twice a day
Results showed a strong positive effect of St. John’s wort,
compared with placebo, in reducing somatic anxiety, psychic
anxiety, overall anxiety scores, and physician and patient
ratings of somatoform disorder symptoms
Somatoform disorders have complex
relationship with anxiety disorders
Open trial with St. John’s
wort plus valerian in
anxiety and depression
Valerian was used in combination with St. John’s wort to
treat patients with comorbid anxiety and depression; the
combination was better than St. John’s wort alone at
reducing anxiety scores
Suggestive improvement of St.
John’s wort with addition of
valerian; very few side effects
RCT with valerian versus
diazepam (Valium) and
placebo in GAD
Randomized, double-blind, placebo-controlled comparison of
valerian with diazepam in GAD, 12 patients per group for
four weeks
; no differences between valerian and placebo,
or between diazepam and placebo
Too underpowered to demonstrate
differences in effectiveness; no
differences in side effects
RCT with Sympathyl versus
placebo; two tablets twice
a day in GAD
Double-blind randomized trial conducted among patients
with mild to moderate GAD in 22 general practices in Paris,
; Sympathyl (n = 130) and placebo (n = 134) groups
were relatively large; after three months the Sympathyl
group showed a 10.6-point decline in the Hamilton Anxiety
Scale score, whereas the placebo group showed an
8.9-point decline
Statistically significant advantage
for Sympathyl compared with
placebo, but size of difference
(1.7 scale points) very small
RCT of passionflower versus
oxazepam (Serax; brand
no longer available in the
United States) in GAD
Each group had 18 patients with GAD
; both groups started
with mean Hamilton Anxiety Scale scores of 20 and ended
with significant reductions to 6; the groups also had the
same level of side effects
Both groups equally positive but
small study with no placebo
group; results unclear
RCT = randomized controlled trial; OCD = obsessive-compulsive disorder; GAD = generalized anxiety disorder.
Information from references 16 through 23.
554 American Family Physician Volume 76, Number 4
August 15, 2007
Herbs for Anxiety
for treating anxiety disorders have no evi-
dence supporting clinical utility. Only
5-hydroxytryptophan appeared to show
clinical effectiveness among the precursor
preparations. Table 6 summarizes the avail-
able evidence relevant to the effectiveness
and safety of 5-hydroxytryptophan.
Although there is some indication that
5-hydroxytryptophan can reduce anxiety
symptoms among patients with anxiety dis-
orders, the evidence is weak. Also, it has been
known to cause eosinophilia-myalgia syn-
drome, a significantly dangerous side effect.
Therefore, the risk/benefit ratio does not
favor physician support of patients choosing
this medication because it is “natural.
Key Recommendations for Physicians
Because use of herbal remedies is increasing,
it is important for family physicians to ask
their patients about such use. Encourag-
ing data support the effectiveness of some
of these products, particularly kava and,
to a lesser degree, inositol. Although none
of these supplements or products are free
of adverse effects, the potential for benefit
seems greater than the risk of harm.
The existing data show that the popular
supplements St. Johns wort, valerian, and
omega-3 fatty acids have little therapeutic
value for anxiety disorders, and their use
should be discouraged in favor of more
effective treatments. In addition, many
Table 5. Evidence Supporting the Effectiveness and Safety of Inositol in Anxiety Disorders
Design Description Comments
RCT crossover
with placebo in
panic disorder
Twenty-one patients with panic disorder were randomly assigned
to 6 g of inositol or placebo twice a day for four weeks and
then switched to the other substance
; during week 4, the
mean number of panic attacks was 3.7 in the inositol group
compared with 6.3 in the placebo group
Panic attack frequency and intensity were
significantly reduced in the inositol group
RCT crossover
with SSRI in
panic disorder
Inositol was compared with fluvoxamine (Luvox) in 20 patients
with panic disorder
; each crossover phase lasted four weeks
(dosage: inositol, 18 g per day, or fluvoxamine, 150 mg per
day); the four-week intervals were separated by a one-week
placebo washout period; overall, both drugs reduced panic
attack frequency and intensity, anxiety scale scores, and clinical
global improvement scores; no meaningful clinical differences
were noted between the two drugs
The absence of a placebo condition is
troubling but, taken together with the
previous trial, inositol appears to reduce
panic disorder symptoms in the short term;
over a one-month interval, inositol showed
effectiveness similar to that of established
SSRI medications for panic disorder
RCT crossover
with placebo
in OCD
The same research team compared inositol and placebo for the
treatment of OCD
; 13 patients with OCD who had failed
SSRI or clomipramine (Anafranil) treatments or who could
not tolerate their side effects used 18 g per day of inositol or
placebo for consecutive six-week treatment intervals; inositol
produced significant reductions in Yale-Brown Obsessive-
Compulsive Scale scores (4.6) compared with the placebo
condition (0.3); reductions in Hamilton Anxiety Scale scores
were not significantly different
Inositol appears to be highly effective
in reducing OCD symptoms but not in
reducing anxiety scale scores; participants
with OCD had failed previous treatment, so
findings may not be typical of patients with
OCD in general
RCT crossover
with placebo
in OCD
Inositol added to SSRI treatments for OCD
; 13 patients with
OCD who had not responded adequately to fluoxetine
(Prozac), fluvoxamine, or clomipramine for at least eight weeks
were given consecutive six-week trials on 18 g per day of
inositol or placebo, in addition to the SSRI medication; inositol
provided no additional benefit
The two studies on treatment-resistant OCD
suggest inositol adds no benefit to SSRI
therapy but may have positive effects on its
own; none of these short studies produced
side effects from inositol that would
suggest risk greater than that of SSRIs
RCT = randomized controlled trial; SSRI = selective serotonin reuptake inhibitor; OCD = obsessive-compulsive disorder.
Information from references 24 through 27.
August 15, 2007
Volume 76, Number 4 American Family Physician 555
Herbs for Anxiety
preparationsthat might be used by patients
to reduce anxiety lack evidence of effective-
ness with anxiety disorders. The availability
of natural treatments that are supported by
clinical evidence and the recognition of those
that are not will help physicians collaborate
with patients using or seeking natural rem-
edies to maximize the potential for benefit
and minimize the potential for harm.
The Authors
SY ATEZAZ SAEED, MD, is a professor and chairman of
the Department of Psychiatric Medicine, Brody School of
Medicine at East Carolina University, Greenville, N.C., and
chief of psychiatry at Pitt Memorial Hospital, Greenville.
Dr. Saeed received his medical degree from Dow Medical
College, Karachi, Pakistan, and completed his residency
training in psychiatry at the Illinois State Psychiatric
Institute, Chicago.
RICHARD M. BLOCH, PhD, is a professor and director of
research in the Department of Psychiatric Medicine, Brody
School of Medicine at East Carolina University. Dr. Bloch
received his doctorate in psychology from the University
of Wisconsin, Madison.
DIANA J. ANTONACCI, MD, is professor and director
of residency training in the Department of Psychiatric
Medicine, Brody School of Medicine at East Carolina
University. Dr. Antonacci received her medical degree
from Southern Illinois University School of Medicine,
Springfield; completed her residency training in psychiatry
at Duke University Medical Center, Durham, N.C.; and
served a fellowship in child and adolescent psychiatry at
East Carolina University.
Address correspondence to Sy Atezaz Saeed, MD, Dept.
of Psychiatric Medicine, Brody School of Medicine at
East Carolina University, 600 Moye Blvd., Suite 4E-100,
Greenville, NC 27834. Reprints are not available from
the authors.
Author disclosure: Nothing to disclose.
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Table 6. Evidence Supporting the Effectiveness and Safety
of 5-Hydroxytryptophan in Anxiety Disorders
Design Description Comments
RCT in panic
Patients with panic disorder (n = 24) exposed to a panic-inducing carbon
dioxide challenge were given a single dose of 5-hydroxytryptophan (200 mg)
or placebo before exposure
; patients with panic disorder showed a
significantly lower occurrence of panic symptoms; patients without panic
disorder did not show any significant effects of the carbon dioxide challenge
This small trial compared patient
responses to an artificial panic-
inducing challenge; it is not clear if
the panic prevention effect would
transfer to real-world situations
RCT on mixed
Double-blind placebo-controlled trial on 45 mixed anxiety disorders, mostly
panic attacks with agoraphobia, compared 5-hydroxytryptophan with
clomipramine (Anafranil) and placebo for eight weeks
; the clomipramine
and 5-hydroxytryptophan were titrated from 25 mg a day to a maximum of
150 mg per day; the clomipramine group showed significant reductions in
Hamilton Anxiety Scale scores compared with placebo, whereas the
5-hydroxytryptophan group showed modest, nonsignificant improvements
No clinically meaningful effect of
5-hydroxytryptophan on reducing
anxiety scale scores
Case reports
on safety
In the past, multiple cases of eosinophilia-myalgia syndrome were reported
among L-tryptophan users; this serious, incurable, potentially fatal
neurologic condition motivated the temporary withdrawal of serotonin
precursors from the market; the pattern of cases suggested they came
from a single brand of contaminated L-tryptophan
L-tryptophan products are back on the
market; there is current speculation
that any brand of L-tryptophan or
L-hydroxytryptophan can elicit this
serious side effect in overdose
RCT = randomized controlled trial.
Information from references 28 and 29.
556 American Family Physician Volume 76, Number 4
August 15, 2007
Herbs for Anxiety
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... Therefore, anxiety disorders are linked to high emotional distress and are characterized by an intense, irrational fear strongly associated with adult panic disorder (Alkozei et al 2014). Recently, the use of natural herbal "green substances" as a remedy in the form of dietary supplements has increased to treat mild to moderate anxiety disorders (Saeed et al 2007). Motor tension, sweating, intense heart, dizziness, fear, and concentration difficulty could be common symptoms (Brown et al 2001;Fricchione et al 2004). ...
... Plants such as Coriandum sativum seeds, Ocimum gratissimum and Citrus aurantifolia, Aspilia africana, Vernonia amygdalena, and Cnidoscolu sacontifolius have been scientifically validated as being effective as sedatives. In traditional medicine, plants such as Fumerica indica, Azadirachta indica, Gelsemium sempervirens, Piper methysticum & Hypericum perforatum, Stachy slavandulifolia, Valeriana officinalis, and Melissa officinalis have been reported to possess anxiolytic action as well as hypnotic effect [7][8][9][10][11][12][13][14][15][16]. ...
... Evidence-based psychotherapies are broadly underutilized, 2 and existing data suggest that some dietary supplements are potentially useful and relatively safe. 2,3,4,5,24,25,26,27 ...
Despite impressive pharmaceutical advances, mental illness remains a leading cause of suffering and disability. Although some dietary supplements appear to respond to some needs not met by prescription medications, several obstacles prevent their study or use. This article proposes government-supported review and safety monitoring of supplements' use in caring for patients with mental illness.
... However, their high cost, important side effects and a rising interest in natural solutions have driven researchers to search for botanical-based formulas [4]. To this end, there are a number of plants that have been described to possess potential sedative and anxiolytic effects [5][6][7][8][9][10][11]. Of note is lemon verbena (Lippia citriodora), which is native to western South America but is also cultivated in the Mediterranean region and Middle East [12]. ...
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The current fast-moving, hectic lifestyle has increased the number of individuals worldwide with difficulties in managing stress, which in turn is also affecting their sleep quality. Therefore, the objective of the current study was to assess a natural plant-based dietary supplement comprised of lemon verbena (Lippia citriodora) extract, purified in phenylpropanoids, in alleviating stress and improving quality of sleep. A double-blind, placebo-controlled study was conducted for 8 weeks, followed by a 4-week washout period. Both validated questionnaires and functional tests were performed during the study, whereas questionnaires were used after the washout. As a result, the group taking the lemon verbena extract significantly reduced their perception of stress after 8 weeks, which was corroborated by a significant decrease in cortisol levels. After the washout period, the subjects reported to present even lower stress levels, due to the lasting effect of the ingredient. As for sleep quality, the subjects taking the supplement reported feeling better rested, with a stronger effect observed in women. Sleep tracking using a wearable device revealed that the supplement users improved their times in the deeper stages of sleep, specifically their percentage of time in deep sleep and REM. In conclusion, lemon verbena extract purified in phenylpropanoids is revealed as a natural solution to help individuals to improve their stress and sleep quality.
... There are increasing preclinical and clinical studies on herbal drugs and anxiety [211]. Though, concerns persist above meager coverage of information in a number of clinical studies [212,214]. ...
Exploration of new drugs targeting anxiety treatment is a major concern worldwide. Medicinal plants are being used as a potential source of novel drugs for anxiety disorders. The objective of this review is to provide information about the healing outcomes of anxiety treatment with natural products. Valeriana officinalis, Citrus aurantium, Commelina benghalensis, Achyranthes aspera, Mimosa pudica, Achillea millefolium, Nymphaea alba, Leonurus cardiac, Camellia sinensis, Turnera aphrodisiaca, Crataegus oxyacantha and Piper methysticum showed promising effects on anxiety in animal models. In clinical studies, passion flower, kava, valerian, St John's wort, and ashwagandha showed the most positive results. More studies are needed for the exploration of the anti-anxiety of medicinal plants. In drugs derived from natural sources have explored many components that are playing an essential role in curing anxiety disorders and associated complications.
... Antidepressant drugs have been used for the treatment of anxiety disorders despite their ineffectiveness in some patients. Several studies have established the effectiveness of using nutritional and herbal treatments for treating depression and anxiety disorders 18,19,20 . ...
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Nutritional modulation can be a factor in sleep quality, with the potential to cause insomnia. Insomnia has negative consequences both on the outcomes of treatment and on health in general. In this retrospective case-control evaluation, individuals with insomnia likely induced by diet therapy treatment and with a reduced tolerance to Bromazepam therapy, were evaluated on the effects obtainable with the administration of a multi-layered, differentiated release nutraceutical formulation containing highly standardized and titrated extracts of valerian (Valeriana officinalis L.), passionflower (Passiflora incarnata L.) and hawthorn (Crataegus oxyacantha L.) distributed under the commercial name of Neurofast ®. A double-check was carried out against individuals with insomnia likely induced by diet therapy who were tolerant to Bromazepam therapy or who, by personal choice, preferred the use of nutraceuticals from the outset. The results demonstrate how the use of the nutraceutical product both as a first solution therapy and as a replacement for Bromazepam therapy significantly reduces insomnia and psychosomatic and autonomic symptoms. The Bromazepam therapy participants showed significantly effective, rapid results leading to complete remission of insomnia. When Bromazepam therapy was replaced with the nutraceutical product clinical remission was maintained, demonstrating a potentially comparable effect in the complete absence of rebound effect. Notably, the symptom 'morning sleepiness', which can be considered an adverse effect of Bromazepam, was detectable at a severe level in the Bromazepam therapy group but completely absent in nutraceuticals groups. The modified release multilayer nutraceutical formulation distributed under the trade name of Neurofast ® proves to be a safe and effective solution in the management of insomnia symptoms even in the presence of autonomic and psychosomatic symptoms. Further studies, more structured and carried out on a larger and selected sample with more stringent criteria, will be necessary to further clarify the aspects taken into consideration.
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Mental illness affects millions of people around the world. Anxiety disorders are one of the most common mental disorders, occurring in 16.6% of the population around the world. Anxiety (anxietas-worry, fear, uneasiness) is a specific psychic state, characterized by an excessive manifestation of emotionality. It occurs under the influence of stress, which in interaction with the genetically innate level of emotional activity and reactivity, causes excessive manifestation of emotionality, which is manifested by excessive changes in the behavior and activation of the autonomic nervous system (dilation of pupils, tachycardia, sweating of the palms, respiratory disorder, GIT disorders, etc.). In mild and reversible forms of anxiety disorders, anxiety can be stimulating and productive. However, in strong forms, anxiety can hinder normal human activity for a long time, which requires therapy. In addition to pharmacological therapy, many herbal medicines have shown efficacy in the treatment of anxiety disorders, as therapeutic agents or in addition to therapy, which is confirmed by numerous scientific studies. Herbal preparations of Passiflora incarnata, Kava-Kava, St. John’s wort, valerian, chamomile, lemon balm, lavender are used for centuries in traditional medicine due to sedative effect and positive mood impact. Studies proving the usefulness of these herbal remedies and their extracts in the treatment of anxiety disorders have been gaining importance over the past several decades.
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Mental illness has long been a part of human history; however, not as long as humans have been using plants for medicinal purposes. Medicinal plants are the source of over 50% of our medications today. Several countries integrate traditional systems of medicine (homeopathic medicine) with international systems of medicine. However, the presence of medicinal plants for anxiolytic and anti-depressant medications is sorely lacking. This is despite a 30-year gap between the last new medications for anxiety and depressive disorders and the availability of ketamine in 2019. Several gaps and lack of access to research regarding the potential benefits of using medicinal plants as anxiolytic and antidepressant solutions create even more difficulties for researchers. In addition to this, the cost of development associated with creating new medications within this field of medicine is incredibly resource and time-intensive. Despite this level of stagnation pharmaceutical companies are still hesitant to approach medicinal plants and phytochemicals as potential sources of pharmaceutical interest. A hesitancy that seems to be echoed by several nations despite the vast amounts of money lost due to symptoms caused by anxiety and depressive disorders. This paper takes an in-depth look at all the issues listed above and more, analyzing the merit of researching/using medicinal plants for anxiolytic and antidepressant purposes, in the past, present, and potentially the future.
Anxiety is a very prevalent mental disorder. γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain and many anxiolytic drugs exert their action through interactions with the GABA receptors. In addition to the GABAergic system, serotonergic, dopaminergic, and noradrenergic systems are also implicated in the development of anxiety and stress in various animal models and humans. Furthermore, involvement of the hypothalamic–pituitary–adrenal axis and dysregulation of the immune system may also mediate stress and anxiety in humans and animals. While a number of anxiolytic drugs are available on the market, dietary supplements and herbal extracts are shown to exert equivalent calming effects with minimal to no addictive or adverse side effects. This chapter describes the pharmacological targets involved in the development of stress and anxiety and the role of various nutraceuticals and dietary supplements that have the potential to reduce anxiety and stress.
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A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. To document trends in alternative medicine use in the United States between 1990 and 1997. Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. A total of 1539 adults in 1991 and 2055 in 1997. Prevalence, estimated costs, and disclosure of alternative therapies to physicians. Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.
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Current serotonin reuptake inhibitor (SRI) treatments for obsessive–compulsive disorder (OCD) provide only partial benefit. A previous study suggested that inositol alone is efficacious in OCD. Ten DSM-IV OCD patients completed a study of 18 g inositol or placebo for 6 wk each in addition to ongoing SRI treatment in a double-blind randomized cross-over design. Weekly assessments included the Yale–Brown Obsessive–Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety scales. No significant difference was found between the two treatment phases.
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The study examined the relationship between mental disorders and the use of complementary and alternative medicine. Data from a national household telephone survey conducted in 1997-1998 (N=9,585) were used to examine the relationships between use of complementary and alternative medicine during the past 12 months and several demographic variables and indicators of mental disorders. Structured diagnostic screening interviews were used to establish diagnoses of probable mental disorders. Use of complementary and alternative medicine during the past 12 months was reported by 16.5% of the respondents. Of those respondents, 21.3% met diagnostic criteria for one or more mental disorders, compared to 12.8% of respondents who did not report use of alternative medicine. Individuals with panic disorder and major depression were significantly more likely to use alternative medicine than those without those disorders. Respondents with mental disorders who reported use of alternative medicine were as likely to use conventional mental health services as respondents with mental disorders who did not use alternative medicine. We found relatively high rates of use of complementary and alternative medicine among respondents who met criteria for common mental disorders. Practitioners of alternative medicine should look for these disorders in their patients, and conventional medical providers should ask their depressed and anxious patients about the use of alternative medicine. More research is needed to determine if individuals with mental disorders use alternative medicine because conventional medical care does not meet their health care needs.
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Objective: Passionflower (Passiflora incarnata) is a folk remedy for anxiety. A double-blind randomized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder. Methods: The study was performed on 36 out-patients diagnosed with GAD using DSM IV criteria. Patients were allocated in a random fashion: 18 to the Passiflora extract 45 drops/day plus placebo tablet group, and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial. Results: Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder. No significant difference was observed between the two protocols at the end of trial. Oxazepam showed a rapid onset of action. On the other hand, significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam. Conclusion: The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage. A large-scale trial is justified.
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Because they found in an earlier study that inositol, an important intracellular second-messenger precursor, was effective against depression in open and double-blind trials, the authors studied its effectiveness against panic disorder. Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, 4-week, random-assignment crossover treatment trial of 12 g/day of inositol. The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration. Side effects were minimal. The authors conclude that inositol's efficacy, the absence of significant side effects, and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder.
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Earlier studies reported that inositol, a simple polyol second messenger precursor, was effective in controlled trials for patients with depression and panic. In this study its effectiveness in obsessive-compulsive disorder was investigated. Thirteen patients with obsessive-compulsive disorder completed a double-blind, controlled crossover trial of 18 g/day of inositol or placebo for 6 weeks each. The subjects had significantly lower scores on the Yale-Brown Obsessive Compulsive Scale when taking inositol than when taking placebo. The authors conclude that inositol is effective in depression, panic, and obsessive-compulsive disorder, a spectrum of disorders responsive to selective serotonin reuptake inhibitors.
BACKGROUND: Synthetic anxiolytic drugs are effective for anxiety, but they are burdened with adverse events. Constraints on resources and time often render treatments such as psychological interventions impracticable. Thus, an effective and safe oral medication would be of considerable interest and a welcome addition to the therapeutic repertoire. OBJECTIVES: To systematically review the evidence regarding the efficacy and safety of kava extract for the symptomatic treatment of anxiety. SEARCH STRATEGY: Computerized literature searches were performed in the databases Medline, Embase, Biosis, AMED, CISCOM and the Cochrane Library (all from their respective inception to June 1998). The search terms used were kava, kawa, kavain, Piper methysticum and Rauschpfeffer (German common name for Piper methysticum). Manufacturers of kava preparations and experts on the subject were contacted and asked to contribute published and unpublished material. In addition, our own files were searched and the bibliographies of all of the studies identified were scanned for further trials. There were no restrictions regarding the language of publication. SELECTION CRITERIA: Randomized, double-blind trials of oral kava extract mono-preparations for the treatment of anxiety were included. Trials comparing kava with placebo were included. Trials assessing kava as one of several active constituents in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: All publications were blinded prior to assessment by a person not involved in the study. Data on patients, interventions, methods, results and adverse events were extracted systematically. Methodological quality of all trials was evaluated using the scoring system developed by Jadad and colleagues. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by the two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Seven trials met the inclusion criteria. All of the reviewed trials suggest superiority of kava extract over placebo. The meta-analysis of three studies using the Hamilton Anxiety Score as a common outcome measure suggests a significant differential treatment effect in favour of kava extract (weighted mean difference: 9.69, 95% confidence interval: 3.54 - 15.83). Adverse events as reported in the reviewed trials were mild, transient and infrequent. REVIEWER'S CONCLUSIONS: These data imply that kava extract is superior to placebo and relatively safe as a symptomatic treatment for anxiety. These findings warrant further and more rigorous investigations into the efficacy and safety of kava extract.
A double-blind placebo-controlled study of 5-HTP and clomipramine was carried out on 45 patients suffering from anxiety disorders (DSM-III). Clomipramine has shown to be effective in that it induced significant improvement on all rating scales as compared to placebo. 5-HTP showed a moderate reduction of the symptomatology on the 90-item symptoms checklist (SCL-90) and the State Scale of the Spielberger State-Trait Anxiety Inventory. Clomipramine and 5-HTP differed in their efficacy in that 5-HTP did not affect the associated depressive symptomatology. The results support the hypothesis that brain serotonergic pathways are involved in the pathogenesis of anxiety disorders, particularly in agoraphobia and panic disorders.
101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines.