Transcript Naturopathic Considerations for Sleep Disorders

Sleep Disorders
Considerations and Treatment
Protocols
Sleep Statistics
o
Over 1.2 million Australians experience sleep
disordersi
o In 2004, the estimated cost of sleep disorders in
Australia was $10.3 billionii
(Chiropractors Association of Australia)
Sleep Statistics
o In Australia, sleep disorders underlie 9.1% of workrelated injuries, 8.3% of depression, 7.6% of non
work-related motor vehicle accidents, 2.9% of
diabetes, 0.9% of kidney disease and 0.6% of
cardiovascular diseaseiii
o According to the Australian Bureau of Statistics, in
1999 almost 4% of the population had recently used a
sleeping medicationiv
(Chiropractors Association of Australia)
What is sleep?
Stages of sleep
Non-REM Sleep
• Stage 1: Light sleep; easily awakened; muscle
activity; eye movements slow down.
• Stage 2: Eye movements stop; slower brain waves,
with occasional bursts of rapid brain waves.
• Stage 3: Considered deep sleep; difficult to awaken;
brain waves slow down more, but still have
occasional rapid waves.
• Stage 4: Considered deep sleep; difficult to awaken;
extremely slow brain waves.
(U.S. Dept of Health and Human Services 2005 pg 11)
REM Sleep
• Eyes move rapidly, with eyelids closed. Breathing is
more rapid, irregular, and shallow. Heart rate and
blood pressure increase. Dreaming occurs. Arm and
leg muscles are temporarily paralysed.
(U.S. Dept of Health and Human Services 2005 pg12)
Sleep Disorders
Common Sleep Disorders and
Symptoms
Insomnia
• Insomnia is an inability to obtain a sufficient amount
of sleep to feel rested and can be characterised
either by difficulty falling or staying asleep.
(Peters 2009)
Insomnia
• Sleep: sleep onset insomnia
• Staying asleep: maintenance insomnia
• Waking refreshed: non restorative sleep
Insomnia
Treatment considerations
Short term treatments:
• Sleep onset: Encourage body to sleep
• Sleep maintenance: Question other body systems
particularly liver/gut nervous system
• Waking unrefreshed: Endocrine/Immune disorders
Issues Initiating sleep
Consider:
• Sleep hormones: progesterone, melatonin
• Neuromodulator: adenosine
• Energy production: mitochondria function, alkaline
environment
• Infections/chronic inflammation – high amount of
cytokine Interleukin 1 and 2 (tryptophan and omega
3 modulates)
Issues maintaining sleep
Consider:
• Hypoxia
• Vestibular imbalances
• Support liver and gut function: i.e. Insulin resistance
and irregular blood sugar control
• Status of anabolic hormone and seratonin
• Adenosine (1 tsp before bed) (Osiecki 2001)
• Omega 3:6 ratio affects total sleep time, most
beneficial 1:4 (Osiecki 2001)
Parasomnias
• From the Latin meaning "around sleep," parasomnias
are a sleep disorder characterised by abnormal sleep
behaviors.
• Parasomnias involve unconscious complex, semipurposeful, and goal-directed behaviors that have
meaning or importance to the individual.
(Peters 2009)
Parasomnias/REM disturbances
Treatment considerations
Short term treatments:
• Check kidney function; neurotransmitters:
acetylcholine, glycine, noradrenalin
• Treat underlying concerns: Referral to professional
(counselor, hypnotherapist etc) to address goaldirected behavior
Sleep Paralysis and Narcolepsy
Sleep Paralysis
Polysomnography shows at least one of the following:
• Suppression of skeletal muscle tone
• Sleep onset REM period
• Dissociated REM sleep
Narcolepsy
Narcolepsy is a sleep disorder characterised by four
classic symptoms:
• Excessive daytime sleepiness
• Cataplexy
• Sleep paralysis
• And hypnagogic hallucinations.
(Peters 2009)
Sucubus and Incubus
http://1.bp.blogspot.com/_512VEbm7xB0/Smbey-wJIkI/AAAAAAAAftI/HdpB8NaSMeE/s400/5.jpg
Sleep Paralysis
Treatment considerations
Short term:
• Patient education about sleep stages; muscle atonia
typically associated with REM sleep
• Avoid chronic sleep deprivation - Sleep hygiene
• Check kidney function; neurotransmitters:
acetylcholine, glycine, noradrenalin
Narcolepsy
Treatment considerations
Short term:
• Nervous system support
Long term:
• Treat underlying concerns, Support
Restless Legs Syndrome
Restless Legs Syndrome
• Restless legs syndrome: neurological movement
disorder characterised by unpleasant feelings in the
legs associated with a need to move.
• Sensations may include aches, burning, tingling, or
the feeling of bugs crawling on the legs.
(Restless Leg Syndrome Australia)
Restless Legs Syndrome
Treatment considerations
Short term:
Lifestyle Considerations
• Application of heat:
• Physical activity: Stretching, not excessive
Avoid triggers
• Alcohol, caffeine, nicotine, some medications
(Restless Leg Syndrome Australia)
Restless Legs Syndrome
Treatment considerations: Short term
Nutritional Considerations:
• Low iron (may disable the dopamine system)
• Magnesium (Osiecki 2001)
• Folic acid, Vitamin E (Osiecki 2001)
Other considerations
• Dopaminergic substances
Dopamine pathway
• L-Tyrosine
• L-DOPA (3,4-dihydroxyphenylalanine)
• Dopamine
Substrates and Cofactors of
Dopamine
• L-phenylalanine
• L-tyrosine
• These conversions require vitamin B6, vitamin C,
and S-adenosylmethionine. (Meyers 2000)
• L-DOPA
• Mucuna pruriens (Velvet Bean)
Products - Dopamine
Inkephalin - Orthoplex
• dl-Phenylalanine 400 mg
• Glutamine 25 mg
• Magnesium oxide 100 mg(equiv. magnesium 60 mg)
• Pyridoxine hydrochloride (vitamin B6)
• 5 mg Thiamine hydrochloride (vitamin B1)
• 50 mg Tryptophan
• 25 mg Zinc gluconate 25 mg (equiv. zinc 3.6 mg)
• 1-3 tablets daily one hour before meals
http://www.bioconcepts.com.au/index.php?p=products&product_id=33
Dopaminergic Substances
Monoamine oxidase inhibitors (MAOIs)
• Nicotiana tabacum (Tabacco)
• Banisteriopsis caapi (Ayahausca, Caapi, Yage)
• Peganum harmala(Harmal, Syrian Rue)
• Passiflora incarnata (Passion Flower
• Tribulus terrestris (Puncture Vine)
Dopaminergic Substances
• Hyperforin and adhyperforin (Hypericum
perforatum)
• L-theanine (Camellia sinensis (Tea Plant, also known
as Black, White, Oolong, Pu-erh, or Green Tea))
• S-adenosyl-L-methionine (SAMe)
Still awake?
Synapse
http://www.umpi.maine.edu/~stump/images/synapse1.gif
Melatonin
• Neurotransmitter and hormone produced by
the pineal gland, brain and retina
• Regulates the sleep-wake cycle by chemically causing
drowsiness and lowering the body temperature
Melatonin pathway
• Tryptophan (facilitated transport by pyridoxine)
• 5-hydroxytryptophan (5 HTP) + Vitamin C (Uni of Bristol 2009)
• Serotonin (serotonergic neurons, pineal gland)
• Melatonin (regulates biological clock – sleep
patterns)
(Siegel et al 1999)
Substrates and Cofactors of
Melatonin: Tryptophan
• Required for melatonin synthesis
• Adequate amounts consumed when total protein
intakes meet recommendations
• Protein in milk and dairy products slightly higher
levels then most other food proteins
• Exposure to high heat can reduce levels in food
• Adults are thought to require 6mg/day (Young and Borgonha
2000)
Products: Tryptophan
Consider product: Inkephalin - Orthoplex
• dl-Phenylalanine 400 mg
• Glutamine 25 mg
• Magnesium oxide 100 mg(equiv. magnesium 60 mg)
• Pyridoxine hydrochloride (vitamin B6)
• 5 mg Thiamine hydrochloride (vitamin B1)
• 50 mg Tryptophan
• 25 mg Zinc gluconate 25 mg (equiv. zinc 3.6 mg)
• 1-3 tablets daily one hour before meals or as
prescribed.
http://www.bioconcepts.com.au/index.php?p=products&product_id=33
Substrates and Cofactors of
Melatonin: Serotonin
This neurotransmitter regulates
• The onset of sleep – converts to Melatonin
• Sensory perception
• Mood and depression
• Low levels may contribute to muscle
weakness and stiffness
Serotonin
Substrates of Serotonin
• L-tryptophan
• Vitamin C (Uni of Bristol 2009)
• 5-hydroxytryptophan (5-HTP) (Meyers 2000)
• Vitamin B6, B3 and Mg cofactors in conversion of
tryptophan to serotonin (Oseiki 2001)
Products: 5-hydroxytryptophan
Consider products such as Thorne or Dr Vera's 5-HTP
• 5 Hydroxytryptophan (5-HTP) 100mg
• Pyridoxal 5-phosphate 5mg
• 1 capsule per day on an empty stomach, with juice
(remember requires vitamin C for conversion)
Products: SAM
• Consider SAM-e Orthoplex
• S-Adenosyl-methionine disulphate tosylate (equiv. SAdenosyl-methionine 200 mg) - 436.80 mg
• Adults: Take 1-3 tablets daily or as prescribed.
Melatonin
Dependent on consumption of:
• L-tryptophan
• Niacin
• Vitamin B6
• Endogenously generated SAM (methionine, folate,
vitamin B12)
• Biopterin
• Pantotherate
• Ascorbate and
• Iron (Kohlmeier 2003 p439-446)
Products: Melatonin
Consider Metagenics Proxan
•
•
•
•
•
•
•
•
5-Hydroxy-tryptophan - 100 mg
S-adenosyl Methionine - 100 mg
dl-Phenylalanine - 100 mg
Potassium phosphate - monobasic - 50 mg
Equiv. potassium - 14.4 mg
Magnesium phosphate - tribasic - 50 mg
Equiv. magnesium - 10.3 mg
Pyridoxal-5-phosphate - 5.0 mg
Cyanocobalamin - 400 microgram
Folic acid - 400 microgram
1 cap/day on an empty stomach with juice/water
Gamma-Amino Butyric Acid
• GABA is the main inhibitory neurotransmitter of the
CNS.
• It is well established that activation of GABA(A)
receptors favors sleep. (Gottesmann C. 2002)
• GABA is also used to regulate anxiety levels (Hettema et al
2006)
GABA Pathway
• Glutamate + enzyme L-glutamic acid
decarboxylase andpyridoxal phosphate (which is the
active form of vitamin B6)
• GABA (gamma-amino butyric acid)
Substrates and Cofactors of GABA
• L-glutamine: food sources – wheat, rye, oats, rice,
dairy, soy, beef, pork, chicken, fish, eggs, beans
(Kohlmeier et al 2003 p280-288)
• Glycine
• Magnesium and Activated B6 (cofactors to convert
glutamine to glutamate to GABA)
• Taurine
• Piper methysticum, Valerian officinalis (increase
GABA available in synaptic cleft), Scutellaira laterfolia
Products: GABA
Consider products such as PreGaba - Orthoplex
• Glutamine 600mg
• Pyridoxal-5-phosphate (vitamin B6) 10mg(equiv.
pyridoxine 6.85mg)
• Taurine 145mg
• Zinc amino acid chelate 25mg(equiv. zinc 5mg)
1-2 capsules per day
http://www.bioconcepts.com.au/index.php?p=products&product_id=80
Herbal Considerations
Hypnotics and sedatives
• Piper methysticum (Kava kava)
• Valeriana officinalis (Valerian)
• Passiflora incarnata (Passion
flower)
• Eschscholzia californica
(California poppy)
• Ziziphus jujuba (Spiny jujube)
• Corydalis yanhusuo (Corydalis )
Herbal Considerations
Sedatives with GIT support
• Matricaria recutita (Chamomile)
• Humulus lupulus (Hops)
Nervine tonics
• Hypericum perforatum (St Johns)
• Verbena officinalis (Vervain)
• Melissa officinalis (Lemon balm)
• Scutellaria lateriflora (Skullcap)
• Avena sativa (Oats)
• Turnera diffusa (Damiana)
Herbal Considerations
Adaptogens
• Withania somnifera
(Ashwaganda)
• Eleutherococcus senticosus
(Siberian ginseng)
• Asparagus racemosus (Shatavari)
Dietary Considerations
Reduce/eliminate caffeine
• Tea
• Soft drinks
• Coffee
• Chocolate
• Cough and cold medicine
• Over-the-counter medicine.
Dietary Considerations
•
•
•
•
Avoid refined CHO - Reg glucose metabolism
Check food sensitivities
Avoid excessive fluid at night
Avoid stimulants
Dietary Considerations
Consume foods that help you sleep
• Tryptophan: protein, particularly milk/dairy
• Foods high in 5HT: bananas, pineapples, walnuts
(Helander and Some 2000)
• Magnesium : Wholegrains, nuts and seeds,
spinach, legumes, potatoes, bananas (Kohlmeier 2003 p 708)
Homeopathics
• Aconite 6c/12c - for anxiety, fear, restlessness,
nightmares, after shock
• Arnica 6c - Insomnia from overexertion, bruising of
mind/body, "bed feels hard“
• Coffea 6c - overstimulation of the brain (overactive
mind)
• Chamomilla 6c - Child sleeping with eyes open
(irritable and scream/yell incessantly). Insomnia from
sensitivity to pain - drives from bed
Homeopathics
• Ignatia 6c - following grief (emotional shock - love,
disappointed), light sleep in children - often
jerking/twitching. Emotional upsets.
• Nux Vomica 6c/12c - overindulgence. Insomnia
worse from 3AM to dawn - from too much
study/mental stress. Worse from alcohol or coffee
abuse.
Lifestyle Considerations
Flower Essences
Consider flowers for:
Addressing fear
Reducing constant thoughts
Physical exhaustion
Flower Essence
Range Primary Indication/s
Fear
Grey Spider Flower
ABFE
Terror and fear - nightmares
Dog Rose
ABFE
Niggling fears
Crowea
ABFE
Continual worrying; a “sense of not quite right”
Rock Rose
BFR
Extreme terror or panic
Cherry Plum
BFR
Fear of losing control; sudden outbursts of rage
Mimulus
BFR
Fear of known causes
Aspen
BFR
Fears & worries of unknown origin;
Flower Essence
Range Primary Indication/s
Racing thoughts
Vervain
BFR
Will forces action beyond physical strength; highly
strung; fanatical; perfectionists
White Chestnut
BFR
Constant thoughts, worries, mental arguments
Crowea
ABFE
Continual worrying; a “sense of not quite right”
Emergency
essence
ABFE
Stressful situations, emergencies or accidents
Rescue remedy
BFR
Stressful situations, emergencies or accidents
Flower
Essence
Range Potential Indications
Exhaustion
and Burn out
Macrocarpa
ABFE
Drained; jaded; worn out
Olive
BFR
Exhaustion – physical, mental, emotional
Oak
BFR
Overworks, hides tiredness; nervous breakdown
Gentian
BFR
Those who are easily discouraged
Hornbeam
BFR
For those who feel that they have not sufficient strength
to carry the burden of life
Banksia
Robur
ABFE
Disheartened; lethargic; frustrated
Old Man
Banksia
ABFE
Weary; phlegmatic personalities; disheartened;
frustrated
Lifestyle Considerations
Aromatherapy
Lavandula angustifolia (Guillemain 1989)
Chamomilia recutita
Ylang ylang
Lifestyle Considerations
Light
Difficulty sleep onset: more light in the morning.
Difficulty sleep maintenance: more light in the
afternoon
Music Gentle, soothing, slow music (de Niet 2009, Lai Good 2006)
Acupuncture (Cao et al 2009)
Lifestyle Considerations
Exercise
Reduce muscle tension, stress, increase serotonin
Relaxation techniques
Increase sleep time, fall asleep faster, feel more
rested. Min 20 minutes before going to bed
Sleep hygiene: Do’s
•
•
•
•
•
•
•
•
Go to sleep and get up at the same time each day
Get regular exercise each day
Spend time outdoors or in natural light
Make bedroom as restful as possible
Use bed only for sleep and sex
Take medication as directed
Be comfortable and relaxed
Understand sleep needs
(SDO 2006)
Sleep hygiene: Don’ts
•
•
•
•
•
•
•
•
•
Exercise or other stimulating activity before bed
Consume caffeinated foods before bed
Go to bed too hungry or too full
Nap in the evening before bed
Stay in bed if awake
Share your bed with children or pets
Look at the clock all the time
Smoke or use alcohol to help sleep
Rely on sleeping tablets to help sleep
(SDO 2006)
"Sleep hath seized me wholly"
(William Shakespeare – Cymebline)
Thank you for listening
Tanya Quod BHSc (Nat); Grad Cert Higher Education
References
•
•
•
•
•
•
•
•
•
•
•
All pictures taken from public domain
i Access Economics (2004). Wake Up Australia: The Value Of Healthy Sleep, report to Sleep Health
Australia, October.
ii Access Economics (2004). Wake Up Australia: The Value Of Healthy Sleep, report to Sleep Health
Australia, October.
iii Access Economics (2004). Wake Up Australia: The Value Of Healthy Sleep, report to Sleep Health
Australia, October.
iv Australian Bureau of Statistics (1999) National Health Survey: Use of Medications, Australia, ABS
Cat.No.4377.0, January.
v Sheldon, S.H. (2005). Sleep in Infants and Children. In T. Lee-Chiong (Ed.), Sleep: A Comprehensive
Handbook (pp. 507-510). Hoboken: John Wiley & Sons, Inc.
vi The National Sleep Research Project – 40 amazing facts about sleep. (2000). Retrieved from
www.abc.net.au/science/sleep/facts.htm
vii The National Sleep Research Project – 40 amazing facts about sleep. (2000). Retrieved from
www.abc.net.au/science/sleep/facts.htm
viii David Brown Jr., W. (2005). Insomnia Prevalence and Daytime Consequences. In T. Lee-Chiong
(Ed.), Sleep: A Comprehensive Handbook (pp. 91-98). Hoboken: John Wiley & Sons, Inc.
ix Zammit, G., Weiner, J., Damato, N., Sillup, G., & McMillan, C. (1999). Quality of life in people with
insomnia. Sleep, 22 (Suppl 2), S379-S385.
Kohlmeier M, (2003) Nutrient Metabolism, Elsevier Ltd, London
References
•
•
•
•
•
•
•
•
•
x Roth, T., & Ancoli-Israel, S. (1999). Daytime consequences and correlates of insomnia in the
United States: results of the 1991 National Sleep Foundation survey. II. Sleep, 22 (Suppl 2), S354S358.
xi Leger, D., Scheuermaier, K., Philip, P., Paillard, M., & Guilleminault, C. (2001). SF-36: evaluation of
quality of life in sever and mild insomniacs compared with good sleepers. Psychosom Med, 63(1),
49-55.
xii David Brown Jr., W. (2005). Insomnia Prevalence and Daytime Consequences. In T. Lee-Chiong
(Ed.), Sleep: A Comprehensive Handbook (pp. 91-98). Hoboken: John Wiley & Sons, Inc.
xiii Poor Sleep Affecting Accuracy And Attitude On The Job. (2007). Retrieved from f t
www.bettersleep.org/Pressroom/poor-sleep-pr.asp
xiv An Intro to Sleep: What is Sleep? (2007). Retrieved from www.talkaboutsleep.com/sleepdisorders/archives/intro.htm
U.S. Department of Health and Human Services (2005) Your guide to healthy sleep NIH Publication
No. 06-5271 November 2005 Viewed 21 May 2010
http://longevity.about.com/gi/o.htm?zi=1/XJ&zTi=1&sdn=longevity&cdn=health&tm=5&gps=344_
1218_1045_529&f=00&su=p736.9.336.ip_&tt=2&bt=1&bts=1&zu=http%3A//www.nhlbi.nih.gov/h
ealth/public/sleep/healthy_sleep.pdf
Gottesmann C. (2002) GABA mechanisms and sleep, Neuroscience 2002;111(2):231-9
Osiecki H (2001) The Physician’s Handbook of Clinical Nutrition. Bioconcepts Publishing, Eagle Farm
Helander A, Some M, (2000) Dietary serotonin and alcohol combined may provoke adverse
physiological symptoms due to 5-hydroxytryptophan, Life Sci 2000; 67: 799-806
References
•
•
•
•
•
•
•
Siegel G, Agranoff B, Albers R, Fisher S, Uhler M. (1999), Serotonin, Basic Neurochemistry, Molecular,
Cellular and Medical Aspects 6th Edition. Lippincott Williams & Wilkins. Viewed 24 May 2010
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=bnchm&part=A946#A949
Donga E, van Dijk M, van Dijk JG, Biermasz NR, Lammers GJ, van Kralingen KW, Corssmit EP, Romijn
JA. (2010) A Single Night of Partial Sleep Deprivation Induces Insulin Resistance in Multiple Metabolic
Pathways in Healthy Subjects. J Clin Endocrinol Metab.
Chiropractors Association of Australia (CAA), Fact Sheet: Interesting Facts and Statistics on Sleep
Viewed 21 May 2010
http://www.chiropractors.asn.au/AM/Template.cfm?Section=Sleep&Template=/CM/ContentDisplay.c
fm&ContentID=1867
Cao H, Pan X, Li H, Liu J. (2009) Acupuncture for treatment of insomnia: a systematic review of
randomized controlled trials, J Altern Complement Med. 2009 Nov;15(11):1171-86.
Lai H, Good M, (2006) Music improves sleep quality in older adults, Journal of Advanced Nursing
Volume 53 Issue 1, Pages 134 - 144 Published Online: 10 Jan 2006
de Niet G , Tiemens B, Lendemeijer B & Hutschemaekers G, Music-assisted relaxation to improve
sleep quality: meta-analysis, Journal of Advanced Nursing Volume 65 Issue 7, Pages 1356 - 1364,
Published Online: 28 Apr 2009
Guillemain J, Rousseau A, Delaveau P. Neurodepressive effects of the essential oil of Lavandula
angustifolia, Ann Pharm Fr. 1989;47(6):337-43.
References
•
•
Arzi A, Sela L, Green A, Givaty G, DaganY & Sobel N, (2009) The Influence of Odorants on
Respiratory Patterns in Sleep, Chemical Senses Advance Access published online on November 16,
2009, Chemical Senses, doi:10.1093/chemse/bjp079
Peters B. (2009) Overview of Common Sleep Disorders. About.com Viewed 23 May 2010
http://sleepdisorders.about.com/od/commonsleepdisorders/a/Sleep_Disorders.htm
•
Restless Leg Syndrome Australia , Fact File on Restless Leg Syndrome. Viewed 21 May 2010
http://www.rls.org.au/faq.php?PHPSESSID=5b4dd226d268310164a013463d59c703
•
•
http://www.scribd.com/doc/503331/Your-Guide-to-Healthy-Sleep
Hurd R (2010) Sleep Paralysis Visions: Demons, Succubi, and the Archetypal Mind. Viewed 21 may
2010 http://www.realitysandwich.com/sleep_paralysis
García-Borreguero D, Williamsa A, (2010) Dopaminergic augmentation of restless legs syndrome.
•
12 March 2010, Sleep Research Institute, Alberto Alcocer 19, 28036 Madrid, Spain
•
•
•
Meyers, Stephen (2000), Use of Neurotransmitter Precursors for Treatment of
Depression, Alternative Medicine Review 5 (1): 64–71.
University of Bristol, Introduction to Serotonin, Retrieved 2009-10-15.
(SDO) Sleep Disorder Australia: South Australian Branch (2006) Sleep Hygiene, Sleep Disorders
Australia, Viewed 21 May 2010, http://www.sleepoz.org.au/files/fact_sheets/AT09%20-
%20Sleep%20Hygiene.pdf
•
•
K. Ekbom & J. Ulfberg (2009) Restless legs syndrome, Journal of Internal Medicine
Volume 266 Issue 5, Pages 419 - 431 Published Online: 20 Aug 2009
References
•
•
•
•
•
•
•
•
Young V, Borgonha S. (2000) Nitrogen and amino acid requirements: the Massachusetts Institute of
Technology amino acid requirement pattern. J Nutr 2000; 130: 1841S-49S
Molecular Psychiatry (2006) 11, 752–762. doi:10.1038/sj.mp.4001845; published online 23 May
2006
Association between glutamic acid decarboxylase genes and anxiety disorders, major depression,
and neuroticism
Hettema J, An S, Neale M, Bukszar J, van den Oord E, Kendler K and Chen X (2006)
Preliminary results from this study were presented at the XIIIth World Congress on Psychiatric
Genetics, October 14–18, 2005 in Boston, MA, USA.
Pittler M, Ernst E, Edzard (2000) , Efficacy of Kava Extract for Treating Anxiety: Systematic Review
and Meta-Analysis, Journal of Clinical Psychopharmacology: February 2000 - Volume 20 - Issue 1 pp 84-89
Earleya C, Allena R, Connorb J, Ferruccic L, Troncosod J (2009), The dopaminergic neurons of the
A11 system in RLS autopsy brains appear normal, Sleep Medicine Volume 10, Issue 10, Pages 11551157 (December 2009)
Cornelius JR, Tippmann-Peikert M, Slocumb NL, Frerichs CF, Silber MH. (2010) Impulse control
disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study.
Sleep. 2010 Jan 1;33(1):81-7.