Sleep Disorders in the Hypermobility syndromes

1. Sleep Disorders in the Hypermobility syndromes Alan G. Pocinki, M.D. Ehlers-Danlos National Foundation Learning Conference July 22-23, 2011

3. Overview • Autonomic nervous system (ANS) regulates all body processes, including sleep • ANS dysfunction is very common in the hypermobility syndromes, and underlies many of its symptoms • The most common type of sleep disorder seen in the hypermobility syndromes appears to have an autonomic basis

4. Basics of the ANS • Sympathetic nervous system: “fight or flight,” the accelerator • Parasympathetic nervous system: “rest and digest,” the brake

5. Adrenaline • Concept of adrenaline reserve • Central paradox: the lower the reserves, the more exaggerated the stress response, or • The more tired you get, the harder it is to sleep

6. Treatment of Autonomic Dysfunction • Better sleep • Address underlying problems: • Dehydration • Low blood sugar • Emotional stresses • Pain • Fatigue

7. Restoring Autonomic Balance • Better sleep—quantity and quality • Adequate—really—pain control • Adequate salt and fluid • Avoid hypoglycemia • Minimize emotional stresses (realistic goals, not negative, guilty • Don’t “push through” fatigue • Take breaks, “time outs”

8. “Your suggestion to ratchet down my level of ‘busy-ness’ [by taking frequent short breaks] to facilitate relaxation is great. It’s helpful and enjoyable. It’s good to have ‘doctor’s orders’ to relax and read a book for a few minutes in the middle of the day!”

9. Non-RestorativeSleep • Frequent arousals and awakenings • Little or no deep sleep Normal Sleep Non-Restorative Sleep

15. Treatment of Sleep Disorders • Good sleep hygiene • Comfortable mattress • Dark and quiet • Elevate head of bed • Medication “regimen” • Multiple medications with complementary effects usually needed • Finding the right combination can be a frustrating trial and error process • Home sleep monitor can be helpful in assessing response

19. Treatment of Sleep Disorders: Medication • Beta blockers • Clonidine • Alpha blockers • Benzodiazepines • Analgesics • Muscle relaxants • Other agents • Trazodone, amitryptiline, doxepin • Neurontin, Lyrica • “Sleeping pills” • Antidepressants

20. Beta Blockers • Propranolol • Start with 10 mg at bedtime • Increase by 10 mg every 4-5 days until fewer awakenings, side effects, or no further benefit • Switch to long-acting if needed • Take some earlier to offset “second wind” • Often need smaller daytime dose as well

21. Other Beta Blockers • Metoprolol • Start with half a 25 mg tablet (tartrate) • Increase by half a tablet every 4-5 days • Add long-acting (metoprololsuccinate) if needed • Nadolol • Safest in asthma • Start with 20 mg • Increase by 20 every 4-5 days • Consider smaller daytime dose • Carvedilol • Start with 3.125 mg • Increase by one tablet every 4-5 days • Add smaller AM dose if needed

22. Clonidine • Clonidine • Start with 0.1 mg • Increase by 0.1 mg no sooner than one week • No more than 0.3 mg • Consider long-acting clonidine (Nexiclon XR™)

23. Alpha Blockers • Prazosin best studied, shown to reduce nightmares in PTSD, where “a hypersensitivity to adrenaline triggered many of their nightmares.” In a VA study, 75-80% of PTSD patients stopped having nightmares. • Usual dose is 4mg • Can worsen orthostatic intolerance • Not clear if combination alpha-beta blockers (e.g. carvedilol) are as effective, but probably not.

24. Benzodiazepines • All have beneficial properties: • Sedative • Anti-anxiety • Muscle relaxant • Anti-movement, anticonvulsant • “Anti-adrenaline” • But also potential problems: • Impair cognition, motor performance • Depress mood, respiration • Cause or worsen fatigue • Tolerance • Dependence • Withdrawal

25. Some Common Benzodiazepines • Clonazepam • Longest-lasting, most likely to have residual effects • Also effective for restless leg, PLMS • Diazepam • Typically lasts about 8 hours • Probably best muscle relaxant • Temazepam • Typically lasts about 7 hours • Capsule limits dosage adjustment • Lorazepam • Typically lasts about 6 hours • Metabolized differently (less variability, interactions)

26. Analgesics • Anti-inflammatories • NSAID’s: Naproxen, Meloxicam, Celebrex™ • Prednisone • Tramadol, short- and long-acting • Narcotics, short- and long-acting, patches • Cymbalta™, Savella™ • Neurontin™, Lyrica™ • Lidoderm™ • Flector™, Voltaren Gel™, Pennsaid™

27. Muscle Relaxants • Cyclobenzaprine • Shown to improve sleep quality in fibromyalgia • Has analgesic, sedative, muscle relaxant properties • Soma • Less sedating, but probably more analgesic effect, especially with narcotics • Skelaxin • Less sedating, some can tolerate daytime doses • Tizanidine • More sedating, high margin of safety • Baclofen • Potent, use for severe painful spasm only

28. Other Agents • Trazodone • Probably most effective at increasing deep sleep • Low dose, 50-150 mg, most people take 50 • Amitryptiline • Also increases deep sleep, especially with pain • Start at 10 mg, most people take 20-40mg • Doxepin • Enhances sleep more at lower doses • 10 mg tablet, liquid, or Silenor™ 3 mg, 6 mg • DDAVP (Desmopressin)?

29. “Sleeping Pills” • Zolpidem, short- and long-acting • Doesn’t reduce arousals or improve sleep architecture • Onset/maintenance, e.g. until other meds effective • Retrograde amnesia • Zolpidem usually lasts 5 hours, ER about 7 • Lunesta • Doesn’t reduce arousals or improve sleep architecture • Occasionally helps with sleep onset and maintenance, e.g. until other medications become effective • Usually lasts about 7 hours • Zaleplon • Good for sleep onset, especially getting back to sleep • Lasts 2-3 hours, no cognitive impairment

30. Antidepressants • SSRI’s often cause shallower sleep, more dreams • Prozac worst, Lexapro best • Lowest effective dose, consider liquid formulations • Cymbalta sleep neutral if taken in AM • Tricyclics generally improve sleep, but often cause daytime sedation • Wellbutrin impairs sleep if taken late in day, so take once-daily (XL) form early in day or consider AM only dosing of twice a day (SR) form

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32. ONLY THE TWO-LEGGED KIND!

33. “I think your diagnosis was spot on!  I had the prescription for the beta blockers filled immediately and ... taking it appears to make a significant difference in my quality of sleep.  I am already starting to feel more refreshed in the morning.” 

34. Summary • The most common type of sleep disorder seen in the hypermobility syndromes appears to be characterized by excessive sympathetic activity at night • Medications to suppress, offset, or block this excess activity are effective in improving sleep, measured both by polysomnography and symptoms • Replenishing autonomic reserves, minimizing daytime stresses, and improving daytime autonomic balance also help improve sleep, which in turn improves daytime function, which in turn improves circadian rhythms and sleep, which …..

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