Sleep Disorders in the Hypermobility syndromes

Sleep Disorders in the Hypermobility syndromesAlan G. Pocinki, M.D.Ehlers-Danlos National Foundation Learning ConferenceJuly 22-23, 20111

2OverviewAutonomic nervous system (ANS) regulates all body processes, including sleepANS dysfunction is very common in the hypermobility syndromes, and underlies many of its symptomsThe most common type of sleep disorder seen in the hypermobility syndromes appears to have an autonomic basis3Basics of the ANSSympathetic nervous system: fight or flight, the acceleratorParasympathetic nervous system: rest and digest, the brake

4AdrenalineConcept of adrenaline reserveCentral paradox: the lower the reserves, the more exaggerated the stress response, orThe more tired you get, the harder it is to sleep

5Treatment of Autonomic DysfunctionBetter sleepAddress underlying problems:DehydrationLow blood sugarEmotional stressesPainFatigue 6Restoring Autonomic BalanceBetter sleepquantity and qualityAdequatereallypain controlAdequate salt and fluidAvoid hypoglycemiaMinimize emotional stresses (realistic goals, not negative, guiltyDont push through fatigueTake breaks, time outsBetter sleep will help replenish reserves, but doing all these other things will help you sleep better7Your suggestion to ratchet down my level of busy-ness [by taking frequent short breaks] to facilitate relaxation is great. Its helpful and enjoyable. Its good to have doctors orders to relax and read a book for a few minutes in the middle of the day!8Non-Restorative SleepFrequent arousals and awakeningsLittle or no deep sleep

Normal SleepNon-Restorative Sleep9

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14Treatment of Sleep DisordersGood sleep hygieneComfortable mattressDark and quietElevate head of bedMedication regimenMultiple medications with complementary effects usually neededFinding the right combination can be a frustrating trial and error processHome sleep monitor can be helpful in assessing response 15

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So how do we get from here to here18Treatment of Sleep Disorders: MedicationBeta blockersClonidineAlpha blockersBenzodiazepinesAnalgesicsMuscle relaxantsOther agentsTrazodone, amitryptiline, doxepinNeurontin, LyricaSleeping pillsAntidepressants

Antidepressants not usually treatment but can affect sleep19Beta BlockersPropranololStart with 10 mg at bedtimeIncrease by 10 mg every 4-5 days until fewer awakenings, side effects, or no further benefitSwitch to long-acting if neededTake some earlier to offset second windOften need smaller daytime dose as well20Other Beta BlockersMetoprololStart with half a 25 mg tablet (tartrate)Increase by half a tablet every 4-5 daysAdd long-acting (metoprolol succinate) if neededNadololSafest in asthmaStart with 20 mgIncrease by 20 every 4-5 daysConsider smaller daytime doseCarvedilolStart with 3.125 mgIncrease by one tablet every 4-5 daysAdd smaller AM dose if needed21ClonidineClonidineStart with 0.1 mgIncrease by 0.1 mg no sooner than one weekNo more than 0.3 mg Consider long-acting clonidine (Nexiclon XR)22Alpha BlockersPrazosin 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 4mgCan worsen orthostatic intoleranceNot clear if combination alpha-beta blockers (e.g. carvedilol) are as effective, but probably not.23BenzodiazepinesAll have beneficial properties:SedativeAnti-anxietyMuscle relaxantAnti-movement, anticonvulsantAnti-adrenalineBut also potential problems:Impair cognition, motor performanceDepress mood, respirationCause or worsen fatigueToleranceDependenceWithdrawal24Some Common BenzodiazepinesClonazepamLongest-lasting, most likely to have residual effectsAlso effective for restless leg, PLMSDiazepamTypically lasts about 8 hoursProbably best muscle relaxantTemazepamTypically lasts about 7 hoursCapsule limits dosage adjustmentLorazepamTypically lasts about 6 hoursMetabolized differently (less variability, interactions)25AnalgesicsAnti-inflammatoriesNSAIDs: Naproxen, Meloxicam, CelebrexPrednisoneTramadol, short- and long-actingNarcotics, short- and long-acting, patchesCymbalta, SavellaNeurontin, LyricaLidodermFlector, Voltaren Gel, Pennsaid26Muscle RelaxantsCyclobenzaprineShown to improve sleep quality in fibromyalgiaHas analgesic, sedative, muscle relaxant propertiesSomaLess sedating, but probably more analgesic effect, especially with narcoticsSkelaxinLess sedating, some can tolerate daytime dosesTizanidineMore sedating, high margin of safetyBaclofenPotent, use for severe painful spasm only

27Other AgentsTrazodoneProbably most effective at increasing deep sleepLow dose, 50-150 mg, most people take 50AmitryptilineAlso increases deep sleep, especially with painStart at 10 mg, most people take 20-40mg DoxepinEnhances sleep more at lower doses10 mg tablet, liquid, or Silenor 3 mg, 6 mgDDAVP (Desmopressin)?28Sleeping PillsZolpidem, short- and long-actingDoesnt reduce arousals or improve sleep architectureOnset/maintenance, e.g. until other meds effectiveRetrograde amnesiaZolpidem usually lasts 5 hours, ER about 7LunestaDoesnt reduce arousals or improve sleep architectureOccasionally helps with sleep onset and maintenance, e.g. until other medications become effectiveUsually lasts about 7 hoursZaleplonGood for sleep onset, especially getting back to sleepLasts 2-3 hours, no cognitive impairment29AntidepressantsSSRIs often cause shallower sleep, more dreamsProzac worst, Lexapro bestLowest effective dose, consider liquid formulationsCymbalta sleep neutral if taken in AMTricyclics generally improve sleep, but often cause daytime sedationWellbutrin 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) form30DO YOU HAVE ANY DATA?31ONLY THE TWO-LEGGED KIND!32I think your diagnosis was spot on! I had the prescription forthe beta blockersfilled 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. 33SummaryThe most common type of sleep disorder seen in the hypermobility syndromes appears to be characterized by excessive sympathetic activity at nightMedications to suppress, offset, or block this excess activity are effective in improving sleep, measured both by polysomnography and symptomsReplenishing 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 ..34IS HOW YOU GET BETTER!35