An Integrative Approach to Insomnia

1. An Integrative Approach to Insomnia Audra Fox, MD 40th Annual CME Conference for Physician Assistants 24 October 2013

2. Objectives • Discuss insomnia and traditional treatments • Define CAM and commonly misunderstood terms • Discuss briefly the 5 domains as defined by the NIH • Use the 5 domains to discuss CAM therapies for insomnia • I have no financial disclosures or conflicts of interests.

3. Insomnia • repeated difficulty with the • initiation • duration • maintenance • or quality of sleep • occurs despite adequate time and opportunity for sleep • results in some form of daytime impairment.

4. 3 Categories of Insomnia • Acute or adjustment insomnia • lasts up to 3-6 months • acute situational stress such as a new job or an upcoming deadline or examination • typically resolves when the stressor is no longer present or the individual adapts to the stressor • Transient insomnia • Last for about 1 week • often recurs when new or similar stresses arise in the patient’s life. • Chronic or persistent insomnia • lasts longer than 6 months • can be associated with a wide variety of medical and psychiatric conditions • 3 subtypes

5. 3 subtypes of Chronic / Persistent Insomnia • Secondary insomnia • medical and psychiatric problems • menopause, GERD, advanced age, chronic pain • pseudoephedrine, beta-blockers, inhalers • chronic use of drugs and alcohol, including caffeine • Primary sleep disorders • circadian rhythm disorders • central sleep apnea-insomnia syndrome • inadequate sleep syndromes • periodic limb movement or restless leg syndrome • Idiopathic insomnia - sleeplessness without a known cause • Avoid aspartame (Nutritional Medicine)

6. Lack of Sleep • adversely impacts performance • increasing risk for accidents • increased risk • cardiovascular disease • cancers • metabolic disorders • autoimmune disorders • infection • obesity • chronic inflammatory processes

7. What is good sleep? • Wake up rested and enough energy for the day.

8. What controls sleep? • Circadian cycles - “body clock” • Daily variations of physiological functions • regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus • Secretion of melatonin • Drop in core body temperature

9. Circadian cycle • Forced disruption of circadian cycles in animals reduces life span. • Shift work is associated with increased risk for physical and mental illness, especially GI disorders and depression. • It is interesting to note that there is a prominent cyclic signature to many mental disorders including manic-depression, bipolar processes, MDD recurrent, etc. Is it possible that these are somehow related to circadian dysrhythmias?

10. Treatment Options for Insomnia • Traditional Western Medicine • CAM / Integrative Medicine

11. Am Fam Physician. 2007 Aug 15;76(4):517-526. • Treatment Options for Insomnia • KALYANAKRISHNAN RAMAKRISHNAN, MD, and DEWEY C. SCHEID, MD, MPH, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma • http://www.aafp.org/afp/2007/0815/p517.html

12. Treatment Options for Insomnia • Traditional Western Medicine • CAM / Integrative Medicine

13. NIH Definitions • Conventional / Western / Allopathic medicine • practiced by holders of M.D. and D.O. degrees and by allied health professionals, such as physical therapists, psychologists, and registered nurses • CAM – complimentary and alternative • “Healing philosophies, approaches, therapies that mainstream Western medicine does not commonly use, accept, study, understand or make available” • Complimentary - the use of CAM together with conventional medicine • Alternative - use of CAM in place of conventional medicine • Integrative - a practice that combines both conventional and CAM treatments for which there is evidence of safety and effectiveness

14. Complementary and Alternative Medicine Use Increasing • 40-60% Americans use CAM each year • Overwhelming majority seek care from their physician BEFORE they see an alternative provider • 1999, NIH created NCCAM – Nat’l Center for Complimentary and Alternative Mecidine. Eisenberg DM et al Ann Intern Med 2001;135:344

15. Complementary & Alternative Medicines(5 domains identified by the NIH) • Biologically based • Manipulative & Body-based • Energy Medicine • Mind-Body Medicine • Whole Medical System

16. I - Biological Based • Dietary supplements • Botanicals / Herbal products • Probiotics

17. L-tryptophan and 5-HTP • Precursors to melatonin • have not been proven effective in treating insomnia • there are concerns that they may be linked to eosinophilia-myalgia syndrome (EMS) • a complex and debilitating systemic condition with multiple symptoms including severe muscle pain. • 5-HTP readily crosses the blood-brain Barrier. (Bruni O 2004; Sarzi Puttini 1992) • 50-100 mg, 30-60 min prior to bedtime

18. The Melatonin Buzz • Hormone secreted by the pineal gland • Plays a role in sleep-wake cycle • The dramatic decline in the variation of our experience of the natural environment has affected melatonin cycles. • extensive daytime sheltering from natural light and nighttime use of artificial light have reduced the range of human biological functions by altering natural MT cycles contributing to systemic health dysfunctions ( Yun, 2005) • Endogenous MT can also be effectively increased with light management. • The blue end of the light spectrum which is present in natural and artificial light suppresses MT. • Blue-blockers, lights or lenses that block the short wavelength of visible light have been shown to facilitate increases in evening MT. (Raloff J, 2006) • Dusk simulation, dimming ambient light for an hour or two prior to bedtime also appears to help increase endogenous MT production (Naiman R, 2006).

19. Melatonin – interesting info • Caffeine, nicotine and alcohol interfere with MT production. • NSAIDs, beta-blockers (propranolol and atenolol) suppress MT. • Benzodiazepines, diuretics, and calcium channel blockers can interfere with synthesis of MT (Burnham, 2001; McEvoy, 2001; Bratman, 2001) • Electromagnetic fields, which occur in the vicinity of electrical devices such as bed stand clocks and hairdryers, can suppress MT (Reiter, 1994)

20. Melatonin, cont • Physiologic dose is 0.3 mg at night • Pharmacological dose is 2-5 mg • May induce hypothermia • May elevate levels during the day causing drowsiness • Doses for cancer range from 20 mg to 80 mg • SL by-passes liver metabolism • 2 mg sustained release administrated to pts age 55-80 was significantly more effective than placebo in improving sleep (Wade et al. 2007) • Vitamin B6 and B12 - promote MLT production

21. B12 - Methylcobalamin • In several animal studies, methylcobalamin injections: • improved production of melatonin • (Inoué,1994) • enhanced melatonin-induced circadian phase shifts • (Ikeda, 1998; Takahashi, 1993). • Methyl-B12 donates a methyl group to S-adenosyl l methionine (SAM-E), which donates a methyl group in the production of melatonin. Therefore, transmethylation by methyl-B12 may promote melatonin biosynthesis. • ( Pfohl-Leszkowicz, 1991; Sitaram, 1995).

22. B12 cont • Clinically, several case studies and small studies describe success using high dose oral methylcobalamin in adolescents and adults who suffered from sleep disorders, some intractable to numerous medications • ( Ohta, 1991; Okawa, 1998; Mayer, 1996; Tomoda, 1994). • Interestingly, these children did not demonstrate B12 deficiency; in fact, their B12 levels were normal or elevated. This may be related to an undetected inability to absorb vitamin B12, due to a methylation defect or another derangement preventing transport into the cell. • Some discrepancies exist in studies between oral and IM • PO 1500-3000 mcg / day – does not seem to be as effective • IM 1000 mcg q 1-4 weeks – more effective

23. B6 - Pyridoxine • involved in the synthesis of the neurotransmitters • serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid (GABA) in the brain and nerve cells, • may support mental function (mood) and nerve conduction. • Any deficiency of pyridoxine can quickly lead to insomnia and a profound malfunctioning of the central nervous system. • necessary for hemoglobin synthesis and red blood cell growth, maintaining healthy immune system function, and prevention of atherosclerosis.

24. B3 - Niacinamide • Increases serotonin • Increase REM sleep • 1-3 g / day • Can cause elevation in LFTs • Can be used in combination with L-Trytophan

25. Glycine • Nonessential amino acid • beef, poultry, fish and seafood • Inhibitory neurotransmitter • Used to treat schizophrenia • Waking up in the middle of the night • Reduces core body temperature • Reduces fragmentation of sleep architecture • Promotes longer periods spent in deep slow-wave sleep (Yamadera W, et al 2007)

26. Magnesium • 300-500 mg / day • Improve efficiency in patients with insomnia associated with restless legs syndrome or periodic limb movements

27. Valerian • The German Commission E, ESCOP and WHO all recognize the use of valerian for restlessness and as a mild sleep-promoting agent in nervous or anxiety-induced sleep disturbances. • Preparation & Dose • Infusion: Pour 5 ounces over 3-5 grams (1 tsp) valerian root and steep for 10-15 minutes (Wichtl, 1994). Drink before bed or 2-3 times per day as needed. • Tincture: 1-3 ml 1-3 times day (1:5, 70% alcohol) • Standardization: Extracts are often standardized to contain 0.3-0.8% valerenic acid. • Clinically tested products available in the US include: • Sedonium® (Lichtwer Pharma AG, Germany, distributed by Lichtwer Pharma US, Inc). Ethanolic extract (LI 156). Dose used in clinical trials 600 mg before bed. • Valerian Night-time® (Dr. Willmar Schwabe GmbH & Co., Germany, distributed by Nature’s Way Health Products, Inc). Hydroethanolic extract of valerian and lemon balm (Melissa officinalis). Dose used in clinical trials 1-4 tablets/d (valerian 160 mg/lemon balm 80 mg tablet). • Alluna Sleep® (Zeller AG, Switzerland, distributed by GlaxoSmithKline). Extract of valerian and hops (Humulus lupulus) (Ze 91019). Dose used in clinical trials: 1-3 tablets/d (valerian 500 mg/hops 120 mg per tablet). • NIH - 14 page handout

28. Valerian & Lemon Balm • widely known for their relaxant effects • In a study by Muller, 918 children with hyperkinesis and dyssomnia were treated with for 4 weeks with “Euvagel,” a combination of valerian and lemon balm. Seventy percent of children with hyperkinesis and 80% of insomnia improved significantly (Muller, 2006).

29. Ashwagandha • Withanolides, key constituents in the plant, induced an anxiolytic effect comparable to that produced by lorazepam after being administered orally to rats once daily for five days. • For sleep disturbances, ashwagandha used with lorazepam mitigated negative side effects of benzodiazepines • Preparation and dose: • Crude herb: 1-6 grams per day of the dried root, taken in 2-3 divided doses • Tincture (1:5): 2-4 milliliters, taken 3 times daily • Extract: 500 mg 2-3 times per day standardized extracts containing 2.5% withanolides

30. Hops • Widely used by practitioners of herbal medicine in Europe and North America for treatment of • insomnia, mania, anxiety, toothache, and nerve pain. • The German Commission E Monographs list hops as approved for anxiety and sleep disturbance. • Small studies have looked at the combination of valerian and hops for insomnia and suggested helpful effects (Koetter, 2007; Morin, 2005; Fussel, 2000). • Recommended dose is 300-500 mg before bed either in capsule or tincture.

31. II - Manipulative & Body Based • Spinal manipulation • Massage therapy • “Movement Therapies” • Feldenkrais method • Alexander technique • Pilates • Rolfing Structural Integration • Trager psychophysical integration

32. Massage and Aromatherapy • Massage has long been known to enhance relaxation and improve sleep patterns. While massage alone is an effective method for relaxation, studies suggest that massage with essential oils (called aromatherapy), particularly lavender (Lavandula angustifolia), may result in improved sleep quality, more stable mood, increased mental capacity, and reduced anxiety. • Clinical studies have found participants who received massage with lavender felt less anxious and more positive than participants who received massage alone.

33. Chiropractic • No well-designed studies have evaluated the effect of chiropractic care on individuals with insomnia, but chiropractors report that spinal manipulation may improve symptoms of the condition in some individuals. In these cases, spinal manipulation may have a relaxing effect on the nervous system.

34. III - Energy Medicine • Magnet therapy • Light therapy • Qi gong • Reiki • Healing touch • Ki Iki Jutsu • Acupuncture

35. Light Therapy • In 1982 The National Institute of Health identified winter depression and coined the term, ‘SAD’ for Seasonal Affective Disorder • The scientists found that 'SAD' was related to an imbalance in the body's natural circadian rhythms. The Circadian rhythm, or the body’s inner clock governs the timing of sleep, hormone production, body temperature, and other biological functions. • In 1984 these pioneering scientists discovered that exposure to bright white light is very effective at treating seasonal affective disorder. • For many years doctors had relegated light therapy to the periphery of credible science. It wasn’t until 2001 that researchers from NIH, Thomas Jefferson Medical University and Apollo Health fully understood how exposure to specialized bright light, stimulates the production of brain chemicals to relieve the symptoms associated with seasonal depression • Dr. George Brainard’s team at Thomas Jefferson Medical University, identified a photo receptor in the human eye, responsible for reacting to light and controlling the production of melatonin

36. Acupuncture • From World Health Organization - Insomnia • Zhang, 1993 (110) • 60 per group • Group comparison • Auricular acupressure • Medication (diazepam plus chlorohydrate) • After 1 month of treatment, sleep was restored to normal or markedly improved in:• 59/60 in the test group• 20/60 in the control group. • Luo et al., 1993 (109) • 60 per group • Randomized controlled trial • Auricular acupressure • Medication (phenobarbital, methaqualone or meprobamate) • After the course of treatment, sleep improved in:• 96.7% of the test group• 35.0% of the control group.

37. IV - Mind-Body Medicine • Meditation • Yoga • Deep-breathing exercises • Guided Imagery • Hypnotherapy • Progressive Relaxation • Qi gong • Tai Chi

38. Hypnosis • Insomnia • A matched, randomized trial of hypnosis for insomnia found that hypnosis helped patients get to sleep more quickly than placebo or stimulus control ( Stanton, 1989). • Parasomnias – nightmares, sleepwalking, sleep terror disorders • The results for the patient with the nightmare disorder suggested that the effective element in decreasing the frequency of nightmares may have been the specific hypnotic suggestion to alter the nightmare content. The generalized effects of increased relaxation and improved sleep also contributed to therapeutic efficacy. • Two other patients with sleepwalking and sleep terror disorders were also treated. In both the cases the effective ingredient seemed to be the generalized effects of hypnosis. The case reports suggest that the general lowering of tonic levels due to the anxiolytic effects of relaxation employed during hypnosis was responsible for reducing the incidence of these disorders. • Conclusion: hypnosis is a relatively simple, non-invasive, inexpensive, and potentially effective means of treating nightmare, sleepwalking, and sleep terror disorders. (Kennedy. 2002. A review of hypnosis in the treatment of parasomnias: Nightmare, sleepwalking, and sleep terror disorders. Australian Journal of Clinical and Experimental Hypnosis, 30(2), 99-155.)

39. Tai Chi • Tai Chi Chih Improves Sleep Quality in Older Adults • Researchers at the University of California, Los Angeles, conducted a randomized controlled trial, funded in part by NCCAM, to determine whether tai chi chih could improve sleep quality in healthy, older adults with moderate sleep complaints. • In the study, 112 individuals aged 59 to 86 participated in either tai chi chih training or health education classes for 25 weeks. Participants rated their sleep quality based on the Pittsburgh Sleep Quality Index, a self-rate questionnaire that assesses sleep quality, duration, and disturbances. • The results of the study showed that the people who participated in tai chi chih sessions experienced slightly greater improvements in self-reported sleep quality. • The researchers concluded that tai chi chih can be a useful nonpharmacologic approach to improving sleep quality in older adults with moderate sleep complaints, and may help to prevent the onset of insomnia.

40. V - Whole Medical System • Naturopathy • Homeopathy • TCM - Traditional Chinese Medicine • Ayurveda

41. Naturopathy • Sleep Hygiene • Aromatherapy - lavender, chamomile • Chamomile tea before bedtime • Nat’l Sleep Foundation • Sheex • temperature control, moisture transport, breathability (50% better than cotton) • Comfortex blinds or Sound Asleep room darkening curtains • Light therapy

42. Homeopathy • Coffea 30 - Use this medicine when you have mental over-activity due to good or bad news and you are just unable to switch off.  • NuxVomica 30 - When you are under enormous mental strain or pressure, or you have withdrawn recently from alcohol or sleeping tablets. Significant irritability in the daytime will be experienced when you need this medicine. • Lycopodium 30 - If you need this medicine you will wake regularly at around 4am. Your mind will be active at bedtime replaying events from the day over and over. You will dream a lot and talk or laugh in your sleep. • Arsenicum 30 - Your wakeful time will be between 12 and 2am and you will feel anxious and very restless. If you dream, they will be dreams of danger.  • Cocculus 30 - Use this medicine when you are overtired and giddy, irritable from being up looking after someone else such as a sick child. • RhusTox 30 - When you cannot sleep because there is pain or discomfort and it makes you feel very irritable and restless so that you want to get up and walk about. • Simillimum – A 2010 randomized, double-blind, placebo-controlled study found that patients who took simillimum for 1 month saw significant increases in duration and quality of sleep. • the homeopathic remedy that produces the set of symptoms most like that which the disease produces Directions: Take your chosen Homeopathic medicine 30 minutes before bed and repeat when you turn the light off. Repeat if you wake in the night and use as long as you are getting relief. If you do not have an improvement stop the medicine.

43. TCM • According to the Chinese Clock, digestion is the strongest in the morning, between 7 am and 9 am for the Stomach, and 9 am to 11 am for the Spleen/Pancreas. Twelve hours later (7 pm to 11 pm) digestion is the weakest, and eating at this time will cause gas, bloating and indigestion, making it difficult for one to fall asleep easily.

44. TCM • Acupuncture • Heart 7 (Shen Men), on the wrist, which helps calm the heart and spirit • At the wrist crease, on the medial side of the flexor carpiulnaris tendon, between the ulna and the pisiform bones. • AnMian, an extra point translated as Peaceful Sleep, which is on the back of the head, where the head meets the neck • Yin Tang, another extra point which is between the eyebrows and promotes relaxation • Chinese Herbs • An MianPian (Sleep Peaceful Formula) for quieting the spirit • Gui Pi Tang (Restore the Spleen Decoction) which strengthens the energy and nourishes the heart • Bao He Wan (Preserves Harmony Pill) which reduces food stagnation and harmonizes digestion (if insomnia is due to eating late at night or indigestion) • Learn more: http://www.naturalnews.com/027348_medicine_insomnia_Chinese.html#ixzz1nF5V74iD

45. Ayurvedic Pharmacology • Pitta person with insomnia - garlic boiled in milk, strained out; milk given at bedtime • Ashwagandha – • The dried root is prepared as a decoction, usually at a daily dose of 3-6 grams. • The dose for tincture (1:5) is generally 5 ml TID. • Ashwaganda is often combined with other adaptogenic herbs, such as ginseng.

46. Conclusion • Treat the underlying problem • Multi-factorial • Long term NSAID use and Menopause • Sleep apnea and shift work syndrome • Individualized medicine – you might have to try more than one thing • Valerian and Hops or Lemon Balm • Melatonin and Glycine • Massage and Aromatherapy

47. Sources • Gaby, A. Nutritional medicine. Concord, NH: Fritz Perlberg Publishing; 2011. • Goldman, E. A new approach to promoting healthy sleep. (12 ed., Vol. 4, pp. 8-9). Holistic Primary Care; 2011. • Insomnia. Maryland: University of Maryland Medical Center. Retrieved from http://www.umm.edu/altmed/articles/insomnia-00096.htm; 2011. • Insomnia. Wikipedia. Retrieved from http://en.wikipedia.org/wiki/Insomnia; 2012. • Monti, D., & Beitman, B. Integrative psychiatry. Oxford, New York: Oxford University Press; 2010. • Rakel, D. Integrative medicine. (2 ed.). Philadelphia, PA: Saunders Elsevier; 2007. • Sleep disorders and cam: What science says. Maryland: National Institute of Health. Retrieved from http://nccam.nih.gov/health/providers/digest/sleepdisorders-science.htm; 2010. • Valerian. NIH Office of Dietary Supplements. Retrieved from http://ods.od.nih.gov/factsheets/Valerian?print=1; 2008.

48. Questions???