Generalized Anxiety Disorder and Panic Disorder in

Women: A Clinical Perspective

http://www.naturalmedicinejournal.com/journal/201208/generalized-anxiety-disorder-and-panic-disorderwomen-clinical-perspective
By Tori Hudson, ND

About the Author

Tori Hudson, ND, graduated from the National College of Naturopathic Medicine
and has served the college in several capacities, including medical director,
associate academic dean, and academic dean. She has been practicing for 26 years,
is currently a clinical professor at The National College of Naturopathic Medicine
and Bastyr University, is medical director of her clinic in Portland, Oregon, and is
director of product research and education for VITANICA. She is the author of the
Womens Encyclopedia of Natural Medicine, 2nd edition. Hudson serves on several
editorial boards, advisory panels, and as a consultant to the natural products
industry. For more information, visit www.drtorihudson.com and
www.instituteofwomenshealth.com.

Abstract

Anxiety disorders are among the most common primary care challenges in a
womens health practice. A comprehensive approach includes identifying the
symptoms, characterizing the disorder, and evaluating whether the patient has a
medical condition such as hyperthyroid, substance abuse, supraventricular
tachycardia, or asthma that manifests as anxiety. Conventional treatments for
generalized anxiety disorder and panic disorder include a range of
antidepressants, sedatives, benzodiazepines, and cognitive therapy. Evidencebased nutraceuticals and botanicals include GABA, L-theanine, passion flower,
skullcap, hops, kava, and lavender oil.

Anxiety in Women
Anxiety disorders, the most common psychiatric disorder in women, are at least
twice as common in women as in men.1 Women suffer from a variety of anxiety
disorders, with the most common being generalized anxiety disorder (GAD), panic
disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder
(OCD), social phobia, and specific phobia.
Generalized Anxiety Disorder
GAD is experienced as excessive anxiety and worry that a woman finds difficult to
control. To qualify as GAD, these symptoms must be present for more days than
not, persist for at least 6 months, and not meet the criteria for the diagnosis of
another anxiety disorder. In women, GAD has a lifetime prevalence of 6.6% with a
1-year prevalence of 4.3%. Generalized anxiety symptoms may also worsen in
women in the premenstrual phase, in the post-childbirth phase, and in the
perimenopause transition. Women with generalized anxiety disorders are also more
likely than men to have coexisting psychiatric disorders.2
Panic Disorder
Panic disorder is twice as common in women as in men, and women are also twice
as likely as men to have panic with agoraphobia.3 Signs and symptoms of a panic
attack may include palpitations, sweating, trembling, shortness of breath, choking,
chest pain, nausea or sudden gastrointestinal symptoms, dizziness or
lightheadedness, derealization, fear of losing control, fear of dying, paresthesias,
chills, and flushing. A patient must have at least 4 of these signs and symptoms for

a diagnosis of panic disorder. Symptoms occur abruptly and reach a peak within 10
minutes. Limited research exists about panic disorders during pregnancy and
postpartum; however, some small studies and case reports have found that panic
symptoms appear to improve during pregnancy. This finding lacks confirmation
with larger studies. Panic symptoms worsened in the postpartum period in some
small studies, but results have been inconsistent.46
Women are more likely than men to relapse after experiencing remission of their
panic and anxiety symptoms.7
Post-traumatic Stress Disorder (PTSD)
The most common traumas contributing to PTSD in women are rape and sexual
molestation.8
Obsessive-Compulsive Disorder
Unlike many other anxiety disorders, obsessive-compulsive disorder (OCD) is
equally common in women and men, although women tend to develop it later in
life, have more coexisting depression, and experience more severe symptoms than
do men.9 Lastly, women are about twice as likely as men to have social phobias
and specific phobias, although men are more likely to seek treatment.10

Differential Diagnosis
Before concluding that an anxiety disorder is the cause of a patients symptoms, it
is important to rule out other medical illnesses and conditions that may manifest as
anxiety. No laboratory tests or imaging studies can confirm a diagnosis of an
anxiety disorder; therefore clinical judgment and a careful clinical history are the
only means to distinguishing an anxiety disorder from other issues that may mimic
or coexist with it.
Symptoms that may require urgent evaluation include chest pain, choking,
dizziness, shortness of breath, palpitations, and numbness and tingling sensations,
which could be signs of a serious medical condition. Examples of medical
conditions that produce anxiety or anxiety-like symptoms include substanceinduced disorders, cardiac disorders (eg, arrhythmia, myocardial infarction),

pulmonary conditions (eg, asthma), and endocrine disorders (eg, hyperthyroidism,

perimenopause and menopause, premenstrual syndrome, high or low blood sugar).
Guideline to differential diagnosis:
Substance-induced or medical causes of anxiety are more likely if
first presentation of symptoms is after the age of 40,
there is a fluctuation in the level of consciousness, or
evidence of autonomic instability exists.
Anxiety is more likely if
the patient is concerned about losing control in her life,
the patient has a family history of anxiety issues,
symptoms present between the ages of 18 and 45, or
the patient has a recent or anticipated stressful event or has agoraphobia.
Substance Abuse
A comprehensive substance abuse history and medication/supplement history is
important in evaluating a patient for anxiety. This includes over-the-counter,
prescription, alcohol or recreational drug use, appetite suppressants, herbs,
nutrients, nicotine, and caffeinated beverages.
Withdrawal from substances, including alcohol, nicotine, caffeine, opiates, or
benzodiazepines, should also be considered as a cause of symptoms. Short-acting
benzodiazepines such as alprazolam may cause withdrawal symptoms between
doses. Caffeinism symptoms (ie, diuresis, insomnia, anxiety, withdrawal headache,
diarrhea, tachycardia, remulous) are similar to symptoms of anxiety disorders.
Women with anxiety disorders often have substance abuse issues as well, maybe
even as a result of medicating their anxiety disorder. In one study, women with
alcohol abuse problems were 2 to 3 times more likely have depression or an

anxiety disorder compared to other women.11 In another related study on this

subject, women with cocaine dependence had anxiety disorders at twice the rate as
did men with cocaine dependence.12
Cardiac Issues
Several cardiac issues have clinical similarities to panic disorder. Women with
supraventricular tachycardia (SVT) are about twice as likely as men to also have
the diagnosis of panic or anxiety, which is often a reason SVT does not get
diagnosed properly.13 This is a good illustration of the importance of considering
SVT in individuals with anxiety symptoms. Other cardiac problems also may
present with anxiety symptoms, including myocardial infarction, mitral valve
prolapse, coronary insufficiency, congestive heart failure, and anemia.
Pulmonary Disorders
Although it is usually possible for the clinician to distinguish between acute
asthma and a panic attack, the two events can share many of the same symptoms
(eg, dyspnea, chest tightness). It can also be difficult to diagnose an anxiety
disorder in a patient who has known asthma or chronic obstructive pulmonary
disease because panic is more common in these patients when they have dyspnea.
This may lead to overuse of their rescue inhalers and corticosteroids, as well as an
increase in hospital admissions.
Endocrine Dysfunction
Hyperthyroidism is a well-known mimic of anxiety disorders with symptoms such
as tachycardia, perspiration, jittery feelings, and more. Hyperthyroidism is 10
times more common in women men than in men and is most prevalent between
ages 30 and 40.14 Hyperthyroidism is also a potential issue during pregnancy and
can be worse postpartum.15 The incidence of hyperthyroidism during pregnancy is
1 in 500.15 Onset or worsening of anxiety during postpartum should instigate
thyroid testing.
Symptoms associated with perimenopause and menopause, such as insomnia,
irritability, and fatigue, can also be confused with an anxiety disorder. On the other
hand, anxiety and panic disorder can be initiated or worsened during the
perimenopausal transition due to hormonal fluctuations.

Endocrinology issues that run the risk of being diagnosed as an anxiety disorder
and escape proper diagnosis include pheochromocytoma, congenital adrenal
hyperplasia, hypoglycemia, the hypercalcemia or hypocalcemia associated with
abnormal parathyroid function, Addisons disease, Cushings syndrome, and
carcinoid syndrome.

Conventional Treatments
Conventional treatment for GAD tends to focus on venlafaxine or buspirone. Other
options include paroxetine, tricyclic antidepressants, and trazodone.
Benzodiazepines are also effective, especially for acute symptoms, but can be more
difficult to manage in the initial treatment phase. Cognitive behavior therapy
(CBT) and cognitive therapy are also helpful, but medications provide benefits that
last over time.16 CBT is also an important intervention: One study showed that 88%
of patients who received CBT were panic-free after one year.17
Panic disorders are definitely more difficult to treat. This is due in part to patients
suspicion and fear of side effects and increased somatic sensitivities. Paroxetine,
sertraline, fluoxetine, fluvoxamine, imipramine, and clomipramine have all been
shown to be more effective than placebo in clinical trials.1822 Benzodiazepines are
also used for panic disorder, but the potential for dependence and withdrawal make
them less appealing for long-term use. A benzodiazepine with a longer half-life,
such as clonazepam, is often a wiser choice than a shorter-acting medication with
greater addiction possibility and dose-to-dose withdrawal problems.

Nutritional and botanical supplements

Fortunately, many excellent nutritional and botanical supplements can reduce the
frequency, severity, and duration of generalized anxiety and panic disorders. It all
starts with managing stress and optimizing lifestyle habits such as sleep, regular
and healthy eating, regular exercise, and reduction of stimulants.
Gamma-aminobutyric acid (GABA)
The primary inhibitory neurotransmitter in the central nervous system, GABA is
synthesized in the brain from the amino acid glutamate with the aid of vitamin B6.

It exerts sedative and anxiolytic effects at the cellular level. Many of the
conventional medications used to treat anxiety disorders work at least in part by
enhancing GABA activity. While this supplement is popular among alternative
practitioners, adequate clinical trials proving its efficacy are lacking.
L-theanine
The major amino acid in green tea, also found in some mushrooms, L-theanine has
been used historically for its relaxing and antianxiety effects and is thought to work
by increasing levels of GABA and serotonin. Evidence suggests that L-theanine
can induce feelings of tranquility and calm.23
Passionflower (Passiflora incarnate)
Passionflower is used for insomnia, digestive upset related to anxiety or
nervousness, GAD, and even symptoms of opiate withdrawal. Symptoms of
anxiety, nervousness, tension, and heightened reactions to stress can occur
especially in women during the premenstrual phase, perimenopause transition, and
postpartum. A double-blind randomized trial comparing passionflower with a
prescription anxiety medication found both treatments equally effective in the
treatment of GAD.24 No significant difference was observed between the 2
treatments, but there were significantly fewer problems related to impairment of
job performance with the passionflower.
Skullcap (Scutellaria lactiflora)
Skullcap has been used historically for insomnia, anxiety, as a nerve tonic and
sedative for nervous tension and spasms. Its principle flavonoids found are baicalin
and wogonin; it is thought that these and the other flavonoid constituents of
skullcap might act as GABA agonists, therefore creating a sedating and anxiolytic
effect.
Hops (Humulus lupulus)
Used as a preservative and flavoring agent in beer production, hops also helps ease
tension, excitability, nervousness, irritability, restlessness, and sleep disorders.
Only a few studies have been conducted on the sedating effects of hops, including

4 in combination products with valerian; thus we cannot separate the potential

benefits of valerian in these studies, which leaves us unclear just how effective
hops is.2527
While hops contains many constituents, including flavonoids and bitter acids, it is
the volatile oils of hops that have been associated with its sedative properties.28 In
particular, the 2-methyl-3-butene-2-ol in the volatile fraction has been identified as
a primary sedative and hypnotic constituent of hops.29
Kava (Piper methysticum)
Kava appears to have at least moderate efficacy in the treatment of anxiety. A
systematic review (from the Cochrane data base) and meta-analysis of randomized
controlled trials in 2000 found a significant overall reduction in anxiety symptoms
with standardized extract of kava.30 In an update of this analysis in 2003, additional
studies were added and again, there was a significant reduction in anxiety in
patients receiving kava extract compared to placebo.30 There is quite a collection of
other studies on kava in treating generalized anxiety, anxiety in postmenopausal
women and perimenopausal women, and other anxiety states. Some studies look at
using kava while tapering benzodiazepines, or using kava with hormone
replacement therapy. Most, but not all, of these studies show efficacy in reducing
anxiety.
The mechanism for the anxiolytic effect of kava is not clear. The research on its
ability to modulate GABA receptors is conflicting; evidence suggests that
kavalactones modulate GABA activity through lipid membrane structure and
sodium channel function rather than by antagonism of the GABA receptors.31,32
Concern regarding the potential hepatotoxicity of kava with cases of liver damage
have been well publicized. Most cases were not well-reported and involved
coingestion of alcohol, excessive dosage, or inappropriate preparations of the plant,
including aerial parts, root, or stem peelings, which are higher in the toxic
alkaloids.33,34 General guidelines for safe use include using aqueous root
preparations standardized for kavalactones and not exceeding 250 mg/day of those
kavalactones. Kava should be avoided in known liver disease and not administered
with alcohol.
Lavender (Lavandula angustifolia)

Lavender oil has also been shown to be effective when delivered orally. Several
clinical studies have demonstrated the benefit of lavender extracts compared to
study drug or placebo in decreasing anxiety and depression. Orally administered
lavender capsules were tested in 1 randomized, double-blind, placebo-controlled
trial.35 The authors concluded that lavender had anxiolytic effects under conditions
of low anxiety, but they were unable to draw conclusions about high anxiety or
clinical anxiety disorders.
Another study of lavender oil for anxiety disorder compared it to placebo. This was
the first double-blind randomized clinical trial to document the anxiolytic efficacy
of oral lavender essential oil for anxiety disorder.36 Researchers concluded that the
lavender oil was both efficacious and safe and had a significant effect on reducing
anxiety symptoms on several anxiety scales and also improved the quality and
duration of sleep and improved general mental and physical health without
sedation or drug-like side effects.
A multicenter, randomized trial was done comparing lavender oil to low-dose
lorazepam in patients with GAD.37 The results demonstrated that the lavender oil
capsules were comparable in results to the conventional study drug; the Hamilton
Anxiety Rating Scale score decreased by 45% in the lavender group and by 46% in
the drug group. By the end of the 6-week trial, it was a 40% decrease in the
lavender group and 27% in the drug group. In addition, the response rate was
52.5% in the lavender oil group vs only 40.5% with the conventional treatment.
Lavender oil capsules can elicit a lavender eructation, nausea, and dyspepsia in
2.6% to 5.2% of patients.

Summary
Some potential cautions are worth noting relative to the herbs and nutrients
discussed here. Intravenous GABA has been known to cause dysphoria and doserelated increases in blood pressure. L-theanine may potentiate the activity of
antihypertensive medications and may decrease the effects of stimulant drugs.
Passionflower, skullcap, and hops could potentiate the actions of barbiturates,
alcohol, and central nervous system depressant medications, including the sedative
effects of antihistamines. Take caution in using hops in cases of depression. In
pregnant or nursing women, each ingredient must be evaluated carefully for safety.
Anxiety disorder in perimenopausal women is common. In these patients, the most
successful outcomes are achieved when the underlying hormonal influences are

addressed. This may be accomplished with botanicals, nutritional supplements,

and/or hormone management. It is important to assess the potential benefits of
estrogen/progesterone in these women. Stabilizing brain chemistry, sleep cycles,
and other menopause symptoms such as hot flashes can be vital to treating anxiety
disorders. The key to success is using black cohosh, maca, another botanical
menopause combination, and/or estrogen/progesterone as the foundation and then
the particular anxiety symptom intervention in addition. This same concept is
effective in women with premenstrual anxiety or premenstrual exacerbation of
anxiety: Use a premenstrual syndrome treatment strategy and then add the anxiety
specific treatment.

References
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3. Eaton W, Kessler R, Wittchen H, Magee W. Panic and panic disorder in the
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9. Nestadt G, Bienvenu O, Cai G, et al. Incidence of obsessive-compulsive

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10. Schneier F, Johnson J, Hornig C, et al. Social phobia. Comorbidity and
morbidity in an epidemiologic sample. Arch Gen Psychiatry. 1992;49:282288.
11. Brady K, Randall C. Gender differences in substance use disorders.
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12. Rounsaville B, Anton S, Carroll K, et al. Psychiatric diagnoses of treatmentseeking cocaine abusers. Arch Gen Psychiatry. 1991;48:43-51.
13. Lessmeier T, Gamperling D, Johnson-Liddon V, et al. Unrecognized
paroxysmal supraventricular tachycardia: potential for misdiagnosis as panic
disorder. Arch Intern Med. 1997;157(5):537-543.
14. Wallis L, ed. Textbook of Womens Health. Philadelphia, PA: LippincottRaven;1998;527-528.
15. Nuwayhid B, Khalife S. Medical complications of pregnancy. In: Hacker N,
Moore J, eds. Essentials of Obstetrics and Gynecology. 2nd ed. Philadelphia,
PA: WB Saunders Co;1992;208-209.
16. Falsetti S, Davis J. The nonpharmacologic treatment of generalized anxiety
disorder. Psychiatr Clin North Am. 2001; 24:99-117.
17. Practice guideline for the treatment of patients with panic disorder. Work
Group on Panic Disorder. American Psychiatric Association. Am J
Psychiatry. 1998;155(5 supl):1-34.
18. Louie A, Lewis T, Lannon R. Use of low-dose fluoxetine in major
depression and panic disorder. J Clin Psychiatry. 1993;54:435-438.
19. Oehrberg S, Christiansen P, Behnke K, et al. Paroxetine in the treatment of
panic disorder: a randomised, double-blind, placebo-controlled study. Br J
Psychiatry. 1995;167:374-379.
20. Pohl R, Wolkow R, Clary C. Sertraline in the treatment of panic disorder: a
double-blind multicenter trial. Am J Psychiatry. 1998;155:1189-1195.

21. Hoehn-Saric R, McLeod D, Hipsley P. Effect of fluvoxamine on panic

disorder. J Clin Psychopharmacol. 1993;13:321-326.
22. Modigh K, Westberg P, Eriksson E. Superiority of clomipramine over
imipramine in the treatment of panic disorder: a placebo-controlled trial. J
Clin Psychopharmacol. 1992;12:251-261.
23. Lu K, Gray M, Oliver C, et al. The acute effects of L-theanine in
comparison with alprozolam on anticipatory anxiety in humans. Human
Psychopharmacol Clin Exp. 2004;19:457-465.
24. Akhondzadeh S, Naghavi HR, Vazirian M, et al. Passionflower in the
treatment of generalized anxiety: a pilot double-blind randomized controlled
trial with oxazepam. J Clin Pharm Ther. 2001;26:363-367.
25. Schmitz M, Jackel M. Comparative study for assessing quality of life of
patients with exogenous sleep disorders treated with a hops-valerian
preparation and a benzodiazepine drug. Wien Med Wochenschr.
1998;148(13):291-298.
26. Muller-Limmroth W, Ehrenstein W. Experimental studies of the effects of
Seda-Kneipp on the sleep of sleep disturbed subjects; implications for the
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27. Gerhard U, Linnenbrink N, Georghiadou C, et al. Vigilance-decreasing
effects of 2 plant-derived sedatives. Schweiz Rundsch Med Prax. 1996;
85(15):473-481.
28. Lee K, Jung J, Song D, et al. Effects of Hummulus lupulus extract on the
central nervous system in mice. Planta Med. 1993;59 (suppl): A691.
29. Hansel R, Wohlfart R, Coper H. Sedative-hypnotic compounds in the
exhalation of hops, II. Z. Naturforsch. 1980;35 (11-12):1096-1097.
30. Pittler M, Ernst E. Kava extract for treating anxiety. Cochrane Database
Syst Rev. 2002;(2):CD003383.
31. Yuan C, Dey L, Wang A, et al. Kavalactones and dihydrokavain modulate
GABAergic activity in a rat gastric-brainstem preparation. Planta Med.
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32. Magura E, Kopanitsa M, Gleitz J, et al. Kava extract ingredients, (_)methysticin and (+/-)-kavain inhibit voltage-operated Na (+)-channels in rat
CA1 hippocampal neurons. Neuroscience. 1997;81:345-351.
33. Coulter D. Assessment of the Risk of Hepatotoxicity with Kava Products.
Geneva: WHO Appointed Committee, 2007.
34. Teschke R, Schwarzenboeck A, Hennermann K. Kava hepatotoxicity: A
clinical survey and critical analysis of 26 suspected cases. Eur J
Gastroenterol Hepatol. 2008;20:1182-1193.
35. Bradley BF, Brown SL, Chu S, Lea RW. Effects of orally administered
lavender essential oil on responses to anxiety-provoking film clips. Hum
Psychopharmacol. 2009;24(4):319-330.
36. Kasper S, Gastpar M, Mller WE, et al. Silexan, an orally administered
Lavandula oil preparation, is effective in the treatment of 'subsyndromal'
anxiety disorder: a randomized, double-blind, placebo controlled trial. Int
Clin Psychopharmacol. 2010;25:277-287.
37. Woelk H, Schlaefke S. A multi-center, double-blind, randomised study of
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Lavender Oil for Anxiety and Depression

http://www.naturalmedicinejournal.com/journal/2012-02/lavender-oilanxiety-and-depression-0

Review of the literature on the safety and efficacy of lavender

By Jeremy Appleton, ND

About the Author

Jeremy Appleton, ND, is a licensed naturopathic physician. He is a graduate of

Reed College and the National College of Natural Medicine. He served on faculty
at NCNM as the nutrition department chair and has also taught at Bastyr
University, where he did his residency. Appleton left his private practice in 1998 to
work in the natural products industry. He is the author of several books and
hundreds of articles on natural medicine. He currently serves as director of
scientific affairs at Integrative Therapeutics.

Abstract
Lavender flower and its extracts have been used, both internally and by olfaction,
for centuries as a treatment for anxiety and depression. Modern analytical research
has identified the main active constituents of the oil; in vitro and animal studies
have begun to elucidate mechanisms of action; and controlled clinical trials in
humans now document lavenders efficacy, safety, and dose. This paper reviews
these developments, with summary details from selected studies, and provides a

preliminary comparison of lavenders efficacy and safety to its main botanical and
pharmaceutical alternatives.

Introduction
Anxiety is a common complaint and may range from every day stress to clinically
relevant symptoms requiring medical intervention. Patients with generalized
anxiety disorder (GAD) can experience excessive anxiety and worry associated
with the stresses of everyday life. Most cases of GAD begin in childhood and can
leadwithout treatmentto a chronic condition, with fluctuating symptoms, often
exacerbated by stressful life events.1 Disturbed sleep has been observed to be
among the most frequent accompanying disorders of generalized anxiety.2
Individuals with anxiety disorder not otherwise specified (AD NOS) also present
with clinically significant symptoms, but they tend to report less worry, negative
affect, depression, and comorbidity than those with GAD.3
The most commonly prescribed agents in the medical treatment of anxiety are
benzodiazepines and selective serotonin reuptake inhibitors (SSRIs).4 The wellknown side effects of benzodiazepines include drowsiness, fatigue, confusion and
disorientation, dizziness, decreased concentration, impaired memory, dry mouth,
and blurred vision. Benzodiazepines can impair the ability to drive or operate
machinery and may thus interfere with essential activities of daily living. They
lower the tolerance to alcohol and are widely reported to cause physical and
psychological dependence and withdrawal symptoms.5 SSRIs, on the other hand,
may cause sedation and fatigue, gastrointestinal disturbances, agitation or
insomnia.6,7 The risks and inconveniences associated with available anxiolytic
pharmaceutical medications may be one of the reasons anxiety disorder is
considered an undertreated condition.8
Herbal preparations have long been a mainstay for treating anxiety and depression.
Some botanical agents, most notably kava (Piper methysticum), have demonstrated
efficacy for clinically diagnosed anxiety disorders.9-13 Others, such as St. Johns
wort (Hypericum perforatum), are clinically efficacious for depression in most,14-25
though not all26,27 clinical studies. Kava, however, has been withdrawn by many
manufacturers due to concerns over potential hepatotoxicity,28-32 even though these
effects may have been primarily due to drug interactions, misuse, and poor quality
extracts of this otherwise well-tolerated phytomedicine; St. Johns worts
popularity has suffered because it was found to stimulate cytochrome P450 34, an
enzyme that metabolizes at least half of the known pharmaceuticals sold today.33 A

safe, non-sedating, nonhabit forming herbal anxiolytic with proven efficacy for
GAD and depression is, therefore, of interest to clinicians.
Throughout history, lavender has been cultivated for its flowers and oils and used
both cosmetically and medicinally. A member of the Labiatae family, lavender is
primarily used either dried or as an essential oil. Historical use includes
documented activity as an antibacterial, antifungal, carminative, sedative, and
antidepressant.34 Lavandula angustifolia, Mill. is the most common species of
lavender utilized for health purposes.35 Lavender is native to the Mediterranean, the
Arabian Peninsula, Russia, and Africa.
Lavender has a high concentration of volatile oils, which impart its distinctive and
pleasing fragrance. The relaxing experience of lavender fragrance led to its
deliberate, therapeutic use in aromatherapy to relieve mild anxiety. Lavender has
been also used internally for mood imbalances such as anxiety, insomnia, and
gastrointestinal distress, including nervous stomach.36

Lavender Constituents
Lavender essential oil is obtained from steam distillation processing of the
flowering tops of L. angustifolia. Modern analytical methods, such as capillary gas
chromatography, have demonstrated that lavender oil contains more than 160
constituents, many of which interact synergistically to contribute to its healing
effects. The main active constituents of lavender oil are linalool, linalyl acetate,
terpinen-4-ol, and camphor. The quantity of the linalyl acetate is determined by the
method of steam distillation as it degrades upon distillation to yield linalool. The
highest content of linalyl acetate is obtained when fresh lavender flowers are steam
distilled right after harvest. Other constituents found in lavender include: cisocimene; terpinen-4-ol, -caryophyllene; lavandulyl acetate; 1,8-cineole; and small
amounts of limonene, geraniol, lavandulol, -pinene, camphene, geranyl acetate,
and neryl acetate.37,38
Relative amounts of bioactive constituents can vary significantly from one
lavender oil to another. The European Pharmacopoeia includes limits or ranges for
the content of the predominant components. Specifically, oils with high
concentrations of esters and low concentrations of cineol and other minor
components are generally considered to be of higher quality because these
parameters indicate that a gentle and careful production process was applied and
that high quality raw materials were used. A high quality lavender extract would
not only comply with this monograph but would ideally exceed those

specifications with a higher content of linalyl acetate (ideally 3345%) and

lavandulyl acetate (1.5%), and a lower limit for the content of cineol (2 %).39

Mechanisms of action
In vitro and in vivo studies have demonstrated multiple possible mechanisms of
action of lavender oil, as well as its individual constituents, which may partly
account for its relaxing effects when taken orally. Lavender oil has potentiated
expression of GABA-A receptors in cell culture;40 it has shown spasmolytic
activity on guinea pig ileum;41 linalool, a main active ingredient of lavender oil,
has been shown in animals to inhibit glutamate binding in the brain;42 linalool has
also inhibited acetylcholine release and influenced ionic conductance in neurons;43
linalyl acetate is described to exert a relaxing effect.44 Lavender oil has reduced
dose-dependently spontaneous motility and caffeine-induced hyperactivity of
mice.45
Lavender oil aromatherapy has been shown to be effective in the management of
anxiety and depression and small and medium-sized controlled and uncontrolled
clinical trials.

Clinical Efficacy of Lavender

Lavender Aromatherapy
Much prior research on lavender has focused on the administration of lavender via
an olfactory route. The anxiolytic activity of lavender olfaction has been
demonstrated in several small and medium-sized clinical trials.46-53 The efficacy of
aromatherapy of lavender is thought to be due to the psychological effects of the
fragrance combined with physiological effects of volatile oils in the limbic
system.54 These calming effects of lavender oil and single constituents may be the
origin of the traditional use of lavender. Lavender oil olfaction has been shown to
decrease anxiety, as measured by the Hamilton rating scale,51 and can increase
mood scores.55The following are selected examples of clinical trials on lavender
aromatherapy:

Dunn and colleagues demonstrated anxiolytic activity of lavender oil

aromatherapy in patients in intensive care units. Subjects received at least 1
session of aromatherapy with 1% lavender essential oil. Significant
anxiolytic effects were noted in the 1st treatment, though 2nd and 3rd
treatments did not appear to be as effective.47

 Alaoui-Ismaili and colleagues found that the aroma of lavender is considered

by subjects to be very pleasant and is correlated with changes in the
autonomic nervous system.56
Tysoe and colleagues conducted a study of lavender oil in burner use on staff
mood and stress in a hospital setting. A significant number of respondents
(85%) believed that lavender aroma improved the work environment
following the use of the lavender oil burners.57
Diego and colleagues demonstrated that people receiving lavender oil (10%)
olfaction for 3 minutes felt significantly more relaxed and had decreased
anxiety scores, improved mood and increased scores of alpha power on EEG
(an indicator of alertness), and increased speed of mathematical
calculations.58
Lewith and colleagues investigated the effects of lavender aromatherapy on
depressed mood and anxiety in female patients being treated with chronic
hemodialysis.59 The effects of aromatherapy were measured using the
Hamilton rating scale for depression (HAMD) and the Hamilton rating scale
for anxiety (HAMA). Lavender aroma significantly decreased the mean
scores of HAMA, suggesting an effective, noninvasive means for the
treatment of anxiety in hemodialysis patients.
Lavender aromatherapy, with or without massage, may also reduce the
perception of pain and the need for conventional analgesics in adults and
children, though more rigorously controlled trials are needed.60
Oral Lavender Supplementation: Anxiety
Lavender oil has also been shown to be effective via the oral route. Several clinical
studies have demonstrated the benefit of lavender extracts in comparison to
reference or placebo in decreasing symptoms of anxiety and depression.
Orally administered lavender capsules (100 mL and 200 mL) were tested in 97
healthy subjects in a randomized double-blind, placebo-controlled clinical trial.61
Film clips were used to elicit anxiety. Measures included anxiety, State Trait
Anxiety Inventory (STAI), mood, positive and negative affect scale (PANAS),
heart rate (HR), galvanic skin response (GSR), and heart rate variation (HRV).
After baseline measurements, capsules were administered. Participants viewed a
neutral film clip, then an anxiety-provoking and light-hearted recovery film clip.

For the 200 mL lavender dose during the neutral film clip, there was a trend toward
reduced state anxiety, GSR, and HR and increased HRV. In the anxiety-eliciting
film, lavender was mildly beneficial in females but only on HRV measures. In
males, sympathetic arousal increased during the anxiety film (GSR). HRV
significantly increased at 200 mL during all 3 film clips in females, suggesting
decreased anxiety. The authors concluded that lavender has anxiolytic effects in
humans under conditions of low anxiety, but they were unable to draw conclusions
about high anxiety or clinical anxiety disorders.
Kasper and colleagues investigated the efficacy of lavender oil (WS 1265) for AD
NOS in comparison to placebo in a primary care setting.62 This study was the first
double-blind, randomized, placebo-controlled trial to document the anxiolytic
efficacy of orally administered lavender essential oil for anxiety disorder. In 27
general and psychiatric practices, 221 adults reporting unspecified anxiety were
randomized to receive 80 mg per day of lavender oil or placebo for 10 weeks with
office visits every 2 weeks. A baseline HAMA total score of ?18 and a total score >
5 for the Pittsburgh Sleep Quality Index (PSQI) were required. The primary
outcome measures were HAMA and PSQI total score decrease between baseline
and week 10. Secondary efficacy measures included the Clinical Global
Impressions scale, the Zung Self-rating Anxiety Scale, and the SF-36 (Quality of
Life) Health Survey Questionnaire. Subjects taking WS 1265 showed a total score
decrease by 16.0 8.3 points (mean SD, 59.3%) for the HAMA and by 5.5 4.4
points (44.7%) for the PSQI compared to 9.5 9.1 (35.4%) and 3.8 4.1 points
(30.9%) in the placebo group (P<0.01 one-sided, intention to treat). WS 1265 was
superior to placebo regarding the percentage of responders (76.9 vs. 49.1%,
P<0.001) and remitters (60.6 vs. 42.6%, P=0.009). Adverse effects were
uncommon and included dyspepsia (4.7% in the treatment group vs 1.8% in the
placebo group) and eructation (3.7% in the treatment group and none in the
placebo group). Lavender had a significant beneficial influence on quality and
duration of sleep and improved general mental and physical health without causing
any unwanted sedative or other drug-like effects. Researchers concluded that the
lavender oil is both efficacious and safe for AD NOS and predicted that it could
emerge as a gentle therapeutic alternative in the treatment of anxiety.
Woelk and Schlaefke conducted a multicenter, double-blind, randomized Phase III
study of lavender oil (Silexan, WS 1265, Dr. Willmar Schwabe, Karlsruhe,
Germany) in comparison to low-dose lorazepam for patients with GAD.63 The
Hamilton Anxiety Rating Scale (HAMA-total score) was used as the primary
objective measurement to monitor changes in the level of tension and relaxation
beginning at baseline through week 6 of the trial. Additional data were collected

using the Self-rating Anxiety Scale, Penn State Worry Questionnaire, SF-36 Health
Survey Questionnaire, and specific sections of the Clinical Global Impressions of
severity disorder. A total of 77 female (76.6%) and male (23.4%) subjects 1865
years of age were randomized into groups. Participants were eligible for the study
if they met the inclusion criteria of a HAMA-total score of greater than 18, as well
as a score equal to or greater than 2 on both anxious mood and tension items.
Secondary objective outcome data were obtained from responder and remission
rate comparisons made between the 2 treatment groups. In order for a participant to
qualify as having a significant response to treatment they were required to have a
reduction of at least 50% in the HAMA-total score during the 6-week trial.
Remission was defined as a HAMA-total score of less than 10 points at the end of
the 6-week study. The results demonstrated that WS 1265 was comparable to the
conventional approach in its ability to promote relaxation.* The HAMA-total score
decreased by 45% in the WS 1265 group and decreased by 46% in the
conventional group. At the conclusion of the 6-week intervention, 40% of the WS
1265 group and 27% of the conventional treatment group were determined to be in
remission. The WS 1265 group had a response rate of 52.5% compared to only
40.5% taking the conventional option. Adverse effects in the WS 1265 group were
uncommon and included nausea (5.2%), eructation (3.9%), and dyspepsia (2.6%).
Oral Lavender Supplementation: Depression
In a 4-week randomized, double-blind study, researchers compared the efficacy of
a tincture of L. angustifolia with imipramine in the treatment of mild to moderate
depression.64 Forty-five adult outpatients who met the Diagnostic and Statistical
Manual of Mental Disorders, 4th edition (DSM-IV) for major depression based on
the structured clinical interview for DSM-IV participated in the trial. Patients had a
baseline Hamilton Rating Scale for Depression (HAMD) score of at least 18. In
this study, patients were randomly assigned to receive lavender tincture (1:5 in
50% alcohol ) 60 drops per day plus placebo tablet (Group A), imipramine tablet
100 mg per day plus placebo drops (Group B), or imipramine tablet 100 mg/per
day plus lavender tincture 60 drops per day (Group C) for 4 weeks. Lavender
tincture at this concentration was found to be less effective than imipramine in the
treatment of mild to moderate depression (P=0.001). In the imipramine group,
anticholinergic effects such as dry mouth and urinary retention were observed,
whereas headache was observed more in the lavender tincture group. The
combination of imipramine and lavender tincture was more effective than
imipramine alone (P<0.0001). Researchers concluded that lavender tincture may
be of therapeutic benefit in the management of mild to moderate depression, but
only as adjuvant therapy.

In an open-label Phase II trial, Stange and colleagues administered 80 mg per day

of lavender oil (Silexan, WS 1265, Dr. Willmar Schwabe Pharmaceuticals,
Karlsruhe, Germany) to 50 patients with neurasthenia, post-traumatic stress
disorder, or somatization disorder for 3 months.65 Using the State Trait Anxiety
Inventory, von Zerssens Depression Scale, and a sleep diary for assessment,
researchers found that state and trait anxiety as well as depression were reduced
and efficiency of sleep was improved significantly. Controlled clinical trials are
needed to confirm whether oral lavender oil is an effective treatment for
depression.
Comparison to Kava, Benzodiazepines, and Antidepressants
To date, lavender has been compared to benzodiazepines,66 paroxetine (an SSRI
antidepressant), and imipramine (a tricyclic antidepressant). It has also been
compared to kava.67 Kava was perhaps the best studied botanical anxiolytic and
was the leading product in this category until concerns about liver toxicity
prompted many companies to discontinue offering it. In a 6-week study, kava was
found to produce a mean reduction of the HAMA score of 10 points, whereas the
mean reduction of that score from lavender (WS 1265) has ranged from 11.3
points (6-week study)63 to 16 points (10-week study),62 suggesting comparable to
superior efficacy. Pharmaceutical anxiolytics (primarily benzodiazepines) typically
produce HAMA reductions in the range of 11 to 15.3, suggesting comparable to
superior efficacy of WS 1265 without the attendant side effects.62,63,68,69
The Hamilton Anxiety Scale is used in most clinical trials of anxiolytic agents for
GAD. In the study by Kasper and colleagues,62 a diagnosis of AD NOS was used
instead, but the HAMA scale was still employed and baseline HAMA scores were
similar across all trials (ie, > 18). At first glance it might appear that patients with
AD NOS responded better to lavender than patients with GAD. However, the study
of lavender for GAD was of shorter duration (6 weeks) than the study of lavender
for AD NOS. In the longer study, the mean HAMA score change at the 6-week
mark was nearly identical to that seen at the end of the 6-week study of patients
with GAD. Therefore, the additional month of therapy at the same dose is likely to
have had additional effects.
In a meta-analysis of 21 double-blind, placebo-controlled trials in patients with
GAD, Hidalgo and colleagues determined average effect sizes for HAMA total
score change versus baseline of 0.50 for pregabalin, 0.45 for hydroxyzine, 0.42 for
venlafaxine XR, 0.38 for benzodiazepines, 0.35 for selective serotonin reuptake

inhibitors (SSRIs) and 0.17 for buspirone.70 The effect size of lavender (WS 1265)
was computed to be 0.75 in AD NOS. The significant reduction of anxiety-related
symptoms in patients treated with lavender was not only evident in the judgment of
the investigators, but was also perceived by the study participants subjectively
according to the results of the self-rating questionnaire.
The effects of lavender extract (WS 1265) and other anxiolytic agents on HAMA
scores are compared in Table 1 below. They are expressed as a mean HAMA score
change.
TABLE 1

Lavender
(WS
1265)62
Lavender
(WS
1265)63
Lorazepam63
Bromazepam71
Oxazepam70
Kava(WS
1490)70

Dose

Mean
HAMA
Length of
HAMA
Diagnosis score
study
score
at baseline
change

80 mg/d

10 weeks AD NOS 26.8

-16

80 mg/d

6 weeks

GAD

25

-11.3

0.5 mg/d

6 weeks

GAD

25

-11.6

3 mg TID
5 mg TID
100 mg (70%
kavalactones)
TID
10-20 mg/d

6 weeks
6 weeks

GAD
GAD

28.07
28.24

-13
-11

6 weeks

GAD

28.35

-10

24 weeks GAD

23.7

-15.3

24 weeks GAD
9-10
GAD
weeks

23.4

-13.3

Escitalopram72
Paroxetine71 20-50 mg/d
Duloxetine68

60-120 mg/d

-11.1

Based upon the available data, it appears that therapy with at least some lavender extracts
is comparable or superior in efficacy to many commonly prescribed anxiolytics,
including benzodiazepines, SSRIs, and kava. The adverse event profile for lavender is the
least severe of these options by a wide margin. In particular, benzodiazepines are well-

known for their significant habit-forming potential, a drawback not found with lavender
preparations.

Adverse Events, Safety and Dosage

The German Commission E Monographs list no contraindications, side effects, or
drug interactions for lavender flower. Internal use of the volatile oil of lavender oil
has been reported to cause nausea73 and drowsiness after excessive intake.74 This
effect may be dose- and/or quality-dependent, as the occurrence of nausea was
higher in the placebo group than in the treatment group (WS 1265) in the largest
and longest controlled clinical trial of lavender oil supplementation.62
In a brief report, Henley and colleagues described 3 cases of otherwise healthy
boys with prepubertal gynecomastia,75 all of whom had normal serum
concentrations of endogenous steroids and none of whom had been exposed to any
known exogenous endocrine disruptors. The repeated topical application of 1 or
more over-the-counter personal care products that contained lavender oil or
lavender oil and tea tree oil was documented for all 3 patients. The authors
performed in vitro tests that suggested weak estrogenic and antiandrogenic
activities of the oils that may have contributed to an imbalance in estrogen and
androgen pathway signaling.
The effective dose of lavender oil is suggested to be 2080 mg per day.36 The bestdesigned clinical studies with the most robust combination of efficacy and
tolerability used 80 mg per day of a well-defined lavender oil. No serious adverse
events during either of the published studies on this extract were reported.

Conclusion
Lavender oil aromatherapy has been shown to be effective in the management of
anxiety and depression and small and medium-sized controlled and uncontrolled
clinical trials. The best validated use of lavender as an anxiolytic agent is oral
supplementation of 80 mg per day of a high-quality, well-defined lavender
essential oil that has a demonstrated efficacy comparable or superior to
benzodiazepines and kava, with a super safety profile.

Conflict of Interest Statement

Jeremy Appleton, ND, is an employee of Schwabe North America, a subsidiary of

Dr. Willmar Schwabe GmbH & Co, which manufactures and distributes WS
1265, discussed in this article.

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magnesium, B vitamins, vitamin D, St Johns wort, ginkgo, SAMe, 5HTP, and ginseng

http://www.naturalmedicinejournal.com/journal/2009-12/treatmentprotocol-naturopathicholistic-treatment-mild-moderate-depression
By Rena Freedenberg, ND

About the Author

Rena Freedenberg, ND, graduated from Michlelet Eden College of Natural

Medicine in Jerusalem, Israel, where she did 2 years of internship in internal
medicine. Freedenbergs practice is located in Beitar Illit, Israel, where she
specializes in womens and childrens healthcare. Her primary interest is in
addressing the underlying causes of illness and improving the health and quality of
life of women and their families.
Depression is a common mental disorder that presents with some or all of the
following symptoms: a depressed mood, a loss of interest in things that once
brought pleasure, feelings of guilt or low self-worth, disturbed sleep patterns,
changes in appetite, a lack of energy, and poor concentration. These symptoms lead
to impairments in an individuals ability to take care of his or her everyday
responsibilities and can become chronic or recurrent.

According the World Health Organization (WHO), depression is common

worldwide, affecting about 121 million people. Untreated depression can lead to
suicide, and the WHO estimates that 850,000 people worldwide commit suicide
every year. Depression is the leading cause of disability worldwide and was the 4th
leading contributor to the global burden of disease for the year 2000, according to
the WHO. Their estimates project that depression will rise to 2nd place in the
global burden of disease listing by the year 2020.
In many patients, mild to moderate depression can be successfully treated with a
variety of naturopathic and holistic options, such as dietary changes, dietary
supplements, exercise, massage, herbs, and sunlight.
Naturopathic medicine is based on the philosophy of addressing the basic
underlying cause of any health condition. Proper nutrition is a foundational
component of any natural medicine program. Nutrition affects mood through the
many substrates and nutrients needed for proper neurotransmitter synthesis and
function. A healthy diet is not only essential for proper neurotransmitter balance,
but it affects the immune system in ways that then affect neurotransmitter function.
The inclusion of exercise is also of utmost importance in any program addressing
mood disorders. In addition to nutritional intervention and exercise, there are many
other therapies that may improve mood in patients with mild depression. Following
are a number of evidence-based, effective alternative/naturopathic treatments for
depression, including dietary supplements, massage, herbs, sunlight, and more.

Anthroposophic Therapy
Anthroposophy is a spiritual science whose practical applications include
biodynamic agriculture, anthroposophical medicinal products, and eurhythmy
(movement as visible speech). Anthroposophic therapy is rooted in a healing
method known as anthroposophical medicine, a branch of anthroposophic
philosophy founded by Austrian philosopher and social thinker Rudolph Steiner in
the 1920s. It utilizes a holistic approach, endeavoring to restore the balance
between the physical, mental, and emotional states of the patient. Anthroposophical
practitioners use medicines based on homeopathic principles and physical therapies
that call upon massage and artistic expression to trigger the patients self-healing
capacity. Anthroposophic medicine uses the anthroposophic view of the human
being as a blend of 3 interdependent aspects: the physical body; the life force,
understood as the source of growth and regeneration and sometimes called the

soul; and the astral body, which mediates between the body and the soul, also
called the ego or consciousness.
A 4-year study of the effectiveness of anthroposophic therapies in the treatment of
depression evaluated 97 outpatients from 42 medical practices in Germany.
Patients ranged from 20 to 69 years old and were referred to anthroposophic
therapies (art, eurhythmy movement exercises, or rhythmical massage) or started
physician-provided anthroposophic therapy (counseling, medication) for
depression. Participants had suffered from depressed mood and at least 2 of 6
further depressive symptoms for a minimum of 6 months. Data were collected
from July 1998 to March 2005.
The authors concluded in outpatients with chronic depression, anthroposophic
therapies were followed by long-term clinical improvement. Although the pre-post
design of the present study does not allow for conclusions about comparative
effectiveness, study findings suggest that the anthroposophic approach, with its
recourse to nonverbal and artistic exercising therapies can be useful for patients
motivated for such therapies.1

Aromatherapy Massage
Aromatherapy is the use of essential oils to treat a variety of conditions.
Naturopathic physicians use aromatherapy to treat depression, anxiety, insomnia,
and stress-related disorders and to manage chronic pain.
Essential oils have been used effectively for centuries as a traditional medicine, but
they have been the subject of few studies. Even in the absence of sufficient studies
to completely explain the pharmacological effects of many essential oils or their
active chemical constituents, the studies that have been done show measurable
pharmacological effects when essential oils enter the blood stream through either
inhalation or topical application.
Researchers at the Medicinal Plant Research Centre, United Kingdom, reviewed
the published clinical trials of psychoaromatherapy in relation to psychiatric
disorders, as well as evidence from mechanistic, neuropharmacological studies of
the effects of essential oils. The authors concluded that aromatherapy may offer
effective treatment for a range of psychiatric disorders. They also found that it does
not appear to pose the risk of adverse effects found with many conventional
psychotropic drugs.2

Various aromatherapy oils, diluted in carrier oil like almond or olive oil, are
massaged into the skin, where they are absorbed into the bloodstream. Below is a
list of some of the essential oils used in the treatment of depression and anxiety.
Clary sage is used for treating insomnia, anxiety, and depression.
Basil lifts fatigue, anxiety, and depression.
Rose acts on the nervous system.
Ylang ylang is used for anxiety, depression, insomnia, and stress.
Sandalwood has sedative properties and is good for treating depression and
tension.
Lavender is used for depression, headache, hypertension, insomnia,
migraine, nervous tension, and other stress-related conditions.
Jasmine increases the beta waves in the frontal lobe, which can create a
more alert and responsive state of mind.
Rosemary relieves headaches and aids clear thinking.
Patchouli has an uplifting effect for depression and anxiety.
Chamomile is very calming; it soothes nerves and helps insomnia.
Geranium is both sedative and uplifting and thus is used for treating nervous
tension, depression, and hormonal and menstrual problems.
A 2007 clinical study published in the Journal of Clinical Oncology looked at the
effectiveness of aromatherapy massage in the management of anxiety and
depression in patients with cancer. Two hundred eighty-eight cancer patients in the
United Kingdom referred to complementary therapy services because of clinical
anxiety and/or depression were randomized to a course of aromatherapy massage
or usual supportive care alone. The authors concluded that aromatherapy massage
does not appear to confer benefit on cancer patients anxiety and/or depression in
the long term but is associated with clinically important benefit up to 2 weeks after
the intervention.3 In other words, aromatherapy is not a cure for depression, but it

may be an effective short-term aid in managing depression and anxiety when used
with other treatment options.
According the World Health Organization (WHO), depression is common
worldwide, affecting about 121 million people.
Another study was conducted with nursing students in Korea to test the
effectiveness of lavender essential oil on insomnia and depression. In a 4-weeklong, single-blind, repeated-measurements experiment, researchers studied 42
female students who complained of insomnia. The lavender fragrance had a
beneficial effect on insomnia and depression in the students, though repeated
studies would be needed to confirm effective proportions of lavender oil and
carrier oil for insomnia and depression.4
A controlled trial conducted in Thailand tested the relaxation properties of ylang
ylang oil. The oil caused a significant decrease in blood pressure, a significant
increase in skin temperature, and a greater sense of calm and more relaxation. The
authors conclude that there is evidence of the effectiveness of ylang ylang oil for
relief of depression and stress in humans.5

Dietary Changes/Supplements
The first line of naturopathic treatment for almost every disease is improved
patient nutrition. Nutrition plays a key role in the onset, severity, and duration of
depression, including daily mood swings. Food patterns preceding the onset of
depression and during a depressive episode are similar. These patterns may include
skipping meals, poor appetite, and a desire for sweets. Depressive symptoms are
exacerbated by nutritional imbalances, including
frequent consumption of caffeine;
sucrose consumption;
deficiencies in vitamins and minerals (biotin, folic acid, and other B
vitamins; vitamin C; calcium; copper; iron; magnesium; or potassium);
excesses of vanadium6,7;
imbalances in amino acids; and
food allergies.

A recent study published in Neuropharmocology demonstrates that physiologically

relevant doses of caffeine can significantly depress adult hippocampal
neurogenesis.8 (Adult neurogenesis has been associated with learning, memory,
and depression). A review published by the Oklahoma State Medical Association
finds that caffeine is a widely used psychoactive substance that has the potential
to contribute to many psychiatric symptoms.9
Sugar intake has been linked to depression. In an article in the Journal of
Depression and Anxiety, the national rate of sugar consumption was shown to
directly affect the prevalence of major depression. The basis for this includes the
relationship between sugar consumption, -endorphins, and oxidative stress.10

Dietary Recommendations
The main dietary focus in treating depression is to ensure that the patients diet is
rich in foods containing omega-3 fatty acids and those containing magnesium,
vitamins B and D, and the antioxidant vitamins A, C, and E. Along with proper
food, sufficient water intake plays a vital role in maintaining proper chemical
balance in the body; even mild dehydration can cause fatigue. The Institute of
Medicine advises that women should consume 2.7 Ls (91 oz) of total water (from
all beverages and foods) each day, and men should average approximately 3.7 L
(125 oz daily) of total water. The panel did not set an upper limit for water
consumption.11

Omega-3 Fatty Acids

Foods that are rich in omega-3 fatty acids have been shown to reduce neuronal
phospholipid turnover. In 1 study, registered difference images showed that the
omega-3 treatment was accompanied by structural brain changes including, in
particular, a reduction in the lateral ventricular volume.12 A 2007 meta-analysis of
trials involving patients with major depressive disorder and bipolar disorder
provided evidence that omega-3 PUFA supplementation reduces symptoms of
depression.13 The foods with the highest amounts of omega 3 are flax seeds, Chia
seeds, walnuts, baked/broiled salmon, soybeans, baked/broiled halibut, sardines,
herring, tofu, and winter squash. Other foods containing omega-3s are canola oil,
olive oil, broccoli, cantaloupe, kidney beans, spinach, grape leaves, Chinese
cabbage, and cauliflower.

Dietary Magnesium

Studies have shown an inverse relationship between magnesium intake and

depression and anxiety.14-16 Patients with depression should add foods that are high
in magnesium to their diet, such as fish, barley, artichokes, buckwheat, oat bran,
almonds, cashews, pine nuts, black beans, white beans, cornmeal, spinach,
broccoli, tomatoes, pumpkin seeds, and soybeans. Whole-wheat flour contains
magnesium, but the magnesium-rich germ and bran are removed in the process of
making white flour. All green vegetables are sources of magnesium because the
center of the chlorophyll molecule contains magnesium.

B Vitamins
The B-complex vitamins are water-soluble vitamins that are essential to mental and
emotional well-being. B-vitamin deficiency is common because B vitamins are
easily destroyed by common lifestyle behaviors such as drinking alcohol and
caffeinated beverages, smoking, and eating foods rich in refined sugars. Studies
have shown that vitamin-B deficiency can be a cause of both depression and
epilepsy and that preventive vitamin B supplementation and sufficient intake
seem very important for secondary and primary prevention of neuropsychiatric
disorders, especially in subjects with a low intake or status of the vitamins.17
When advising patients to supplement with specific B vitamins, it must be
remembered that the patient must also take a B-complex supplement to prevent
imbalances.
Nerve tissue requires vitamin B1 to utilize glucose to produce energy; this vitamin
modulates cognitive performance, especially in the elderly. Folic acid preserves the
brain during its development and preserves memory during aging. Vitamins B6 and
B12, among others, are directly involved in the synthesis of some
neurotransmitters. Vitamin B6 is likely to benefit the treatment of premenstrual
depression. Good sources of B vitamins include the following.
Asparagus, broccoli, spinach, bananas, potatoes
Dried apricots, dates, and figs
Milk, eggs, cheese, yogurt
Nuts and legumes (includes rice, corn, soy beans, string beans, peas, lentils,
mustard, sesame seeds, and poppy seeds)
Fish

 Brown rice, wheat germ, whole grain cereals

Vitamin D
Seasonal affective disorder (SAD) is prevalent when vitamin D stores are typically
low. Researchers note that people suffering from depression, particularly those
with SAD, tend to improve as their levels of vitamin D in the body increase.18
It has been hypothesized that vitamin D increases levels of serotonin in the brain.19
There are individual differences in the amount of vitamin D needed daily based on
geographical location, the time of year, skin type, and amount of sun exposure.
Research is ongoing to establish new standards for recommended daily vitamin D
intake for adults as the importance of proper vitamin D levels becomes more
obvious; currently, tolerable upper intake levels for vitamin D according to the
National Institutes of Health Office of Dietary Supplements is 2,000 IU for adults
and children over the age of 13 and 1,000 IU for children under one year of age.20
In an experiment conducted in 1998, Australian researchers found that vitamin D3
(cholecalciferol) given in doses of 400 IU and 800 IU had significant positive
effects on the mood of healthy individuals. Forty-four people were given either 400
IU of vitamin D, 800 IU of vitamin D, or a placebo for 5 days during the late
winter. Research subjects reported that vitamin D3 had the effect of enhancing a
positive mood and also reducing a negative mood in some cases. The authors
concluded, Vitamin D3 deficiency provides a compelling and parsimonious
explanation for seasonal variations in mood.21 In 1999, a study done by Hollis,
Gloth, and Alam showed that a one-time dose of 100,000 IU of vitamin D
improved symptoms of depression better than light therapy in a small group of
participants who suffered from SAD.22 All of the participants in the vitamin D
group improved according to all depression scale measurements, and the increase
of serum 25-hydroxyvitamin D [25-(OH)D] levels was strongly associated with the
degree of improvement of SAD symptoms.
A study at the Institute of Clinical Medicine in Norway examined the relationship
between serum 25-(OH)D levels and depression in overweight and obese subjects
and assessed the effect of vitamin D supplementation on depressive symptoms.
Researchers found a significant improvement in Beck Depression Inventory scores
after 1 year in the 2 groups given vitamin D but not in the placebo group. There
was a significant decrease in serum parathyroid hormone in the 2 vitamin D groups
without a concomitant increase in serum calcium. There are receptors for
parathyroid hormone (PTH) and 1,25dihydroxyvitamin D in the brain, and there

are clinical and experimental data indicating that PTH and vitamin D may affect
cerebral function.22 The authors concluded that there appears to be a relation
between serum levels of 25-(OH) D and symptoms of depression. Supplementation
with high doses of vitamin D seems to ameliorate these symptoms indicating a
possible causal relationship.23
Dietary sources of vitamin D include milk, salmon, and tuna. The best food source
of vitamin D is salmon, with 530 IU per 3 oz of canned salmon. Salmon is also rich
in omega 3 fatty acids, making it a very important part of a depression prevention
or treatment diet.

Exercise
Research has shown that exercise is an effective but often underused treatment for
mild to moderate depression, even in elderly patients, and has virtually no side
effects.24,25 Researchers at Duke University demonstrated several years ago that
exercise can be an effective antidepressant even for those patients with major
depressive disorder.26 According to a report from the UK Mental Health
Foundation, exercise may be just as effective at treating depression as
antidepressant medicines, and they also claim that being physically active may
help prevent depression in the first place. The UK report also states that exercise
therapy should be used as a first-line treatment for mild depression because it may
be just as effective as antidepressant medicines.27
Exercise has a number of beneficial physiological effects that make it ideal for
treating depression. Exercise has been proven to increase activity in both the
frontal lobe of the brain and the hippocampus. It also has been found to increase
mood-enhancing brain-derived neurotrophic factor levels.28,29 Studies have also
found that exercise increases levels of serotonin, dopamine, and norepinephrine.3035

Physical activity should last at least 20 minutes a session for at least 10 weeks in
order to help improve psychological well-being. Aerobic activities such as brisk
walking, jogging, cycling, swimming, and dancing tend to be the most effective for
treating depression.36

Natural Medicines
Several herbs have been proven to have a beneficial effect on depression and its
symptoms of anxiety, sleeplessness, and inability to concentrate. Following are

some of the most common herbs and supplements used for mild to moderate
depression.
St Johns Wort (Hypericum perforatum)
St Johns wort is a bushy plant with a turpentine-like odor and yellow flowers
whose petals have black dots on the margins. Its extract has been used in various
folk remedies and herbal tinctures since Roman times. It is used extensively in
both the United States and Europe to treat mild to moderate depression.
A German study compared the effectiveness of St Johns wort with imipramine, a
well-known antidepressant. The trials involved 40 outpatient clinics in Germany
with a total of 324 outpatients suffering mild to moderate depression. Participants
were given either 75 mg imipramine twice daily or 250 mg Hyericum perforatum
extract ZE 117 twice daily for 6 weeks. The study concluded that H perforatum
extract is therapeutically equivalent to imipramine in treating mild to moderate
depression and is better tolerated.37
Another German review investigated the efficacy and side effects of H perforatum.
This study looked at 27 trials that included a total of 2,291 patients who met
inclusion criteria. Seventeen trials, with a total of 1,168 patients, were placebocontrolled (16 addressed single preparations, 1 a combination with 4 other plant
extracts). Ten trials (8 single preparations, 2 combinations of Hypericum and
Valeriana) with a total of 1,123 patients compared Hypericum with other
antidepressant or sedative drugs. Most trials were 4 to 6 weeks long. Participants
usually had neurotic depression or mild to moderate severe depressive
disorders. The study concluded that there is evidence that extracts of Hypericum
are more effective than placebo for the short-term treatment of mild to moderately
severe depressive disorders. The proportions of patients reporting side effects
were 26.3% for Hypericum single preparations vs 44.7% for standard
antidepressants and 14.6% for combinations vs 26.5% with amitriptyline or
desipramine. In other words, patients taking standard antidepressant medications
were almost twice as likely to experience side effects as patients taking
Hypericum.38
Until 2004, only 1 randomized controlled trial had been conducted using
Hypericum in patients with severe depression, but it was underpowered and so its
negative findings were questionable.39 With this in mind, German researchers
conducted a study of acute treatment of moderate to severe depression with
Hypericum extract WS 5570 vs paroxetine. The study involved 251 adult

outpatients with acute major depression with total score 22 on the 17-item
Hamilton Depression Scale from 21 psychiatric primary care practices in Germany.
Patients were given either 900 mg/day Hypericum extract WS 5570 (300 mg 3
times/d) or 20 mg paroxetine once per day for 6 weeks. (In initial nonresponders,
doses were increased to 1,800 mg/day Hypericum or 40 mg/day paroxetine after 2
weeks.) The study concluded that Hypericum extract WS 5570 is at least as
effective as paroxetine in the treatment of moderate to severe major depression and
is better tolerated.40
A comprehensive clinical review by British researchers supports the findings of the
various studies above, and the authors note that all studies have found Hypericum
to be less likely to cause side effects than standard pharmaceutical drugs used
currently.41
The mechanism of action with St Johns wort is being investigated. Initial
biochemical studies report that St Johns wort inhibits the uptake of serotonin,
dopamine, and noradrenalin (norepinephrine). However, other in vitro binding
assays carried out using St Johns wort extract demonstrate significant affinity for
adenosine, GABA (A), GABA (B), and glutamate receptors. In vivo, St Johns wort
extract leads to a decrease in the number of beta-adrenergic receptors and an
increase in the number of serotonin 5-HT(2) receptors in the rat frontal cortex and
causes changes in neurotransmitter concentrations in brain areas that are implicated
in depression.
However, there are reasons to be cautious when prescribing St Johns wort, as it
has been found to have significant interactions with some other drugs. In a study
done at the College of Pharmacy in Little Rock, Arkansas, comparisons of pre and
postSt Johns wort phenotypic ratios revealed significant induction of CYP3A4
and CYP2E1 activity.42 Because CYP3A4 is involved in the oxidative metabolism
of more than 50% of all drugs, this suggests that Hypericum extracts are likely to
interact with many more drugs than previously had been realized. Examples of
medications that could be affected include carbamazepine (anticonvulsant and
analgesic), cyclosporine (immunosuppressant), irinotecan (cancer drug),
midazolam (anesthetic), nifedipine (calcium channel blocker), birth control pills,
simvastatin (cholesterol-lowering drug), theophylline (bronchodilator), tricyclic
antidepressants, warfarin (blood thinner), or HIV drugs such as nonnucleoside
reverse transcriptase inhibitors or protease inhibitors. St Johns wort may also
interact with digoxin or digitoxin (cardiac drug), resulting in a decrease in digoxin
blood concentration. There may also be an interaction with triptan-type headache
medications. Examples include naratriptan, rizatriptan, sumatriptan, and

zolmitriptan. In theory, St Johns wort may also interact with certain chemotherapy
drugs such as anthracyclines and may increase antiinflammatory effects of COX-2
inhibitor drugs or nonsteroidal antiiflammatories such as ibuprofen.
Ginkgo Biloba
The Ginkgo biloba tree is an ancient species of tree native to the Asia. Chinese
herbalists have used ginkgo for thousands of years, and it is one of the most widely
studied botanical products. Ginkgo is widely used throughout both the United
States and Europe. Since ginkgo nuts are mildly toxic, most of the ginkgo sold is in
the form of a standardized extract of the leaves of the tree.
Ginkgo has a long history in traditional medicine for treating circulatory disorders
and enhancing memory. Scientific studies throughout the years support the
effectiveness of ginkgo for these problems.43-48 Evidence to date shows that
ginkgo biloba extract (GBE) is primarily effective in the elderly and when treating
disorders that are caused by diminished cerebral blood flow. Laboratory studies
have shown that GBE improves blood circulation by dilating blood vessels and
reducing the stickiness of blood platelets. Ginkgo leaves also contain flavonoids
and terpenoids, which are powerful antioxidants.49,50
Ginkgo biloba can be used to enhance other depression treatments and sometimes
can be used alone instead of pharmaceutical treatments for mild cases of
depression. Even in cases where ginkgo is used as an adjunct to other depression
treatments, it can be helpful as an aid to improving short-term memory by
improving cerebral circulation.
S-adenosylmethionine
S-adenosylmethionine is sold as a nutritional supplement under the marketing
name SAMe. SAMe is also marketed as an approved prescription drug in Russia,
Italy, and Germany. The supplement SAMe is a synthetic form of a compound
formed naturally in the body from the essential amino acid methionine and
adenosine triphosphate. It was first discovered in 1953.
SAMe serves as a primary methyl group donor in various physiological reactions
and is then converted to S-adenosyl-homocysteine.51-54 Clinical trials have shown
that SAMe is effective in treating depression when taken on a regular basis. Other
conditions that SAMe has been shown to help in clinical trials are liver disease and

osteoarthritis. SAMe is required for the biosynthesis of the neurotransmitters

dopamine and serotonin as well as for cellular growth and repair.
Patients with bipolar disorder or anxiety disorders or other psychiatric disease must
be closely monitored while taking SAMe as it has been associated with hypomania
and mania. There are also concerns that SAMe could cause levodopa to be less
effective when taken over a long period of time, so patients with Parkinson's
disease should be advised to avoid this supplement.55
There are a number of side effects associated with SAMe; the most commonly
reported are nausea and other digestive disturbances. Less common side effects
include anxiety, insomnia, increased thirst, increased urination, headache,
hyperactivity, decreased blood glucose levels, skin rashes, dry mouth, and blood in
the stool. Therapeutic doses range from 400 mg per day to 1,600 mg per day,
although higher doses are used empirically in some cases. In contrast, some
physicians recommend lower doses ranging from 50 to 200 mg per day to treat
mild depression in an effort to lessen the risk of triggering the side effects
mentioned above.
5-Hydroxytryptophan
5-Hydroxytryptophan (5-HTP) is a naturally occurring amino acid, a precursor to
the neurotransmitter serotonin, and an intermediate in tryptophan metabolism. 5HTP is effective in treating depression, suppressing appetite, and promoting sleep.
5-HTP increases serotonin synthesis and release, making it useful in the treatment
of conditions thought to be caused or made worse by a lack of serotonin. Care must
be used to avoid serotonin syndrome in patients taking antidepressant medications.
5-HTP is usually extracted from the seeds of Griffonia simplicifolia and sold in 50
mg or 100 mg gelatin or vegetarian capsules.
Siberian ginseng (Eleutherococcus senticosus)
Siberian ginseng, also known as Eleuthero, is an adaptogen that has been used for
centuries in eastern countries, including China and Russia. As an adaptogen, it helps to
control excess cortisol levels and thereby reduces depression.56,57 Although a distant
relative of American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng)
with some overlap in its uses, Siberian ginseng is a distinct plant with different active
chemical components. Ten compounds have been isolated from Siberian ginseng. Its
pharmacological activities are mainly due to lignans and iridoid glycosides, such as
eleutherosides.58 Prized for its ability to restore vigor, increase longevity, enhance overall

health, and stimulate both a healthy appetite and a good memory, it is widely used in
Russia to help the body adapt to stressful conditions and to enhance productivity.

Practitioners of Chinese medicine use Siberian ginseng to restore the balance of qi

and to treat a deficiency of yang in the spleen and kidney. Siberian ginseng is also
an antioxidant, a nervine, an anticholesteremic, and mildly antiinflammatory.
Siberian ginseng is used to help the body deal with physical and mental stressors
such as heat, cold, physical exhaustion, viruses, bacteria, chemicals, extreme
working conditions, noise, and pollution. It works by strengthening the system,
thereby helping to prevent illness. It has been shown to have significant
antidepressant effects in rats that were subjected to the desperation test and
neuropharmacological tests based on the antagonist activity with respect to
reserpine clofelin, and L-DOPA,59 and a Chinese study has shown that Siberian
ginseng exhibited antifatigue, antistress, immunoenhancing effect, central nervous
system activity, and antidepressive effects.60

Phototherapy
Phototherapy is the use of light to treat disease and is a treatment of choice for
SAD. Other indications for bright light therapy include nonseasonal depression,
bipolar depression, chronic depressive disorder, antepartum and postpartum
depression, late luteal phase dysphoric disorder, circadian phase sleep disorders, jet
lag, shift work problems, and behavioral disturbance and insomnia in organic
dementia.
A 2004 study combining bright light exposure and physical exercise showed that
this treatment may be an effective way of relieving depressive symptoms. The
study concluded that problems with sleep, especially initial insomnia, may predict
a good response to treatment using combined light and exercise. Bright light
exposure and physical exercise, even in combination, seem to be well tolerated and
effective on depressive symptoms.61
At the Beer Yaakov Mental Health Center associated with Tel Aviv University,
Israel, a pilot study was conducted using partial sleep deprivation during the
second half of the night, medium (green) wavelength light in combination with
dawn simulation, bright light therapy, and sleep phase advance. The results showed
the procedure to be effective and well tolerated. It affords many advantages, such
as the achievement of a rapid response, no extinction of the therapeutic effect

after 4 weeks of follow-up, safety, high patient compliance, and cost

effectiveness.62

Energy Psychology
Many of the bodys electrical systems and energy fields are understood, readily
verified, and a focus of established interventions. The application of lasers and
magnetic pulsation, for example, can be described in terms of specific, measurable
wavelengths and frequencies that have been found to be therapeutic.63 Other
energies are considered to be of a more subtle nature and have not been directly
measured by reproducible methods. While such subtle energies are generally not
recognized in Western healthcare frameworks, they are at the root of numerous
ancient systems of healing and spiritual development that are not only still in wide
use throughout the world but increasingly being utilized in the West.
Energy psychology has been referred to as acupuncture without needles in
treating mental health disorders. More than two dozen variations of energy
psychology can be identified, with the most well-known being Thought Field
Therapy (TFT), the Tapas Acupressure Technique (TAT), and the Emotional
Freedom Techniques (EFT). Many of these adapt practices and concepts from
acupuncture and acupressure; others borrow from yoga, meditation, qigong, and
other traditional practices. Some practitioners of these modalities describe their
therapeutic mechanism as the activation of electrical signals that are said to
influence brain activity64; others as describe them as catalyzing shifts in putative
energy fields, such as the bodys biofield.65 TFT, TAT, and EFT, each utilizing
techniques derived from acupuncture and acupressure, have received by far the
most attention.
But what is the proof that there is any real effectiveness to these methods?
Evidence is still preliminary, but energy psychology is gaining credence as an
evidence-based treatment. In fact, 1 form has met the American Psychological
Associations criteria as a probably efficacious treatment for specific phobias;
another has met the criteria for maintaining weight loss.66 The limited scientific
evidence, combined with extensive clinical reports, suggests that energy
psychology holds promise as a rapid and potent treatment for a range of
psychological conditions.

Conclusion

A number of alternatives to standard antidepressant medications exist for patients

with mild to moderate depression. An essential first step is to work with the patient
to ensure proper diet and regular exercise. Once this has been done, nutritional
supplementation, herbal medicines, phototherapy, and energy psychologies can be
utilized according to patient needs as described above.

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