1. Insomnia David A. Garfunkel, M.D. August 31, 2005 David A. Garfunkel, M.D. August 31, 2005

2. FIrrelevant Fact FSleep Physiology FJoke FScope of the Problem FDiagnosis FCommercial Break FNon-Pharmacologic Treatment FPharmacologic Treatment FIrrelevant Fact FSleep Physiology FJoke FScope of the Problem FDiagnosis FCommercial Break FNon-Pharmacologic Treatment FPharmacologic Treatment

3. Who was the 2004 U.S. Open Tennis Woman’s Winner?

4. Svetlana Kuznetsova

5. Definitions FSleep is a state of unconsciousness in which the brain is relatively more responsive to internal than to external stimuli FMechanisms within the brainstem and hypothalamus regulate sleep through GABA and acetylcholine FSleep is a state of unconsciousness in which the brain is relatively more responsive to internal than to external stimuli FMechanisms within the brainstem and hypothalamus regulate sleep through GABA and acetylcholine

6. Philagrypnia FAbility to stay alert with very little sleep

7. Purpose of Sleep FSpeculative FNREM sleep may allow decrease in metabolic demand and allow replenishment of glycogen stores FOscillating depolarization's and repolarizations consolidate and and remove redundant or excess synapses FSpeculative FNREM sleep may allow decrease in metabolic demand and allow replenishment of glycogen stores FOscillating depolarization's and repolarizations consolidate and and remove redundant or excess synapses

8. REM sleep FGenerated by mesencephalic and pontine cholinergic neurons FCharacterized by muscle atonia, cortical activation, low voltage desynchronization of the EEG, and rapid eye movements FGenerated by mesencephalic and pontine cholinergic neurons FCharacterized by muscle atonia, cortical activation, low voltage desynchronization of the EEG, and rapid eye movements

9. FREM sleep has both tonic and phasic qualities FOther features include periodic skeletal muscle twitches, increased heart rate variability and increased respiratory rate FREM sleep has both tonic and phasic qualities FOther features include periodic skeletal muscle twitches, increased heart rate variability and increased respiratory rate

10. Circadian sleep rhythm FOne of several intrinsic rhythms modulated by the hypothalamus FWithout external stimulus, the suprachiasmatic nucleus sets the rhythm to approximately 25 hours FA nerve tract directly from the retina helps regulate us to 24 hours days. FMelatonin is a modulator of light entrainment and is secreted maximally by the pineal gland during the night FOne of several intrinsic rhythms modulated by the hypothalamus FWithout external stimulus, the suprachiasmatic nucleus sets the rhythm to approximately 25 hours FA nerve tract directly from the retina helps regulate us to 24 hours days. FMelatonin is a modulator of light entrainment and is secreted maximally by the pineal gland during the night

11. F Insomnia is defined as difficulty with the initiation, maintenance, duration, or quality of sleep that results in the impairment of daytime functioning, despite adequate opportunity and circumstances for sleep.  Patient’s subjective dissatisfaction with the sleep quality and quantity F Insomnia is defined as difficulty with the initiation, maintenance, duration, or quality of sleep that results in the impairment of daytime functioning, despite adequate opportunity and circumstances for sleep.  Patient’s subjective dissatisfaction with the sleep quality and quantity

12. FTransient Insomnia - Symptoms present for less than one week FShort Term Insomnia - Symptoms for 1-4 weeks FChronic Insomnia - Symptoms present for more than one month FTransient Insomnia - Symptoms present for less than one week FShort Term Insomnia - Symptoms for 1-4 weeks FChronic Insomnia - Symptoms present for more than one month

13. Poor Sleep Maintenance FWaking after sleep has been initiated, but before desired waking time

14. FInitiation of Sleep = Time to fall asleep FStandard - less than 30 minutes FSleep Efficiency = Time sleeping/ Time in bed FStandard - Greater than 85% FMay be caused by awakening frequently during the night with subsequent difficulty in re- initiating sleep, or awakening too early without being able to go back to sleep at all FInitiation of Sleep = Time to fall asleep FStandard - less than 30 minutes FSleep Efficiency = Time sleeping/ Time in bed FStandard - Greater than 85% FMay be caused by awakening frequently during the night with subsequent difficulty in re- initiating sleep, or awakening too early without being able to go back to sleep at all

15. FSome patients may not meet any of the above conditions, but awake feeling poorly rested.

16. Sleep Requirements FAverage - 7 1/2 to 8 1/2hrs/night FRange (for adults) - 5-9 hrs/night FSteadily decreases from birth to old age Fnewborns sleep 14-16 hours/24 hours FElderly spend less time sleeping per night, but increase in sleep latency and more frequent arousals make their requirement in bed longer. FAverage - 7 1/2 to 8 1/2hrs/night FRange (for adults) - 5-9 hrs/night FSteadily decreases from birth to old age Fnewborns sleep 14-16 hours/24 hours FElderly spend less time sleeping per night, but increase in sleep latency and more frequent arousals make their requirement in bed longer.

17. What do you call a nun who sleep walks?

18. A Roamin’ Catholic

19. Scope of the Problem  2003 Sleep in America poll, which included 1,506 adults ages 55 to 84 from various parts of the United States, found a prevalence of insomnia in 48 percent.

20. Scope of the Problem F1997 survey of almost 2000 HMO patients showed that 10% had current major insomnia as defined as taking more than 2 hours to fall asleep each night. FOnly 5% spoke to their physician about it FOver 38 million prescriptions per year for sleeping pills F1997 survey of almost 2000 HMO patients showed that 10% had current major insomnia as defined as taking more than 2 hours to fall asleep each night. FOnly 5% spoke to their physician about it FOver 38 million prescriptions per year for sleeping pills

21. Consequences FMood Disturbance FDepression and/or Anxiety FPoor memory FDifficulty concentrating FMotor vehicle and other accidents FMood Disturbance FDepression and/or Anxiety FPoor memory FDifficulty concentrating FMotor vehicle and other accidents

22. Normal Sleep Physiology FStages F1 - light sleep, 5-10% of total sleep time, transition between awake and asleep F2 - 40-50% of total sleep time F3,4 - deep or delta wave sleep, occurs mostly early in the night FREM sleep, 20-25% of sleep FAll 4 stages repeat in ultradian rhythm of about 90 minutes FStages F1 - light sleep, 5-10% of total sleep time, transition between awake and asleep F2 - 40-50% of total sleep time F3,4 - deep or delta wave sleep, occurs mostly early in the night FREM sleep, 20-25% of sleep FAll 4 stages repeat in ultradian rhythm of about 90 minutes

23. FThere are 4-5 cycles in a normal night’s sleep FFirst REM- 10 minutes, but later REM periods may exceed 60 minutes FThere are 4-5 cycles in a normal night’s sleep FFirst REM- 10 minutes, but later REM periods may exceed 60 minutes

24. Diagnosis- other sleep disorders FHypersomnia - Excessive sleepiness, despite up to 12 hrs./night of sleep FGradual onset FUsually appears before age 25 FRecurrent hypersomnia - Kleine Levin Syndrome FMay be due to depression FHypersomnia - Excessive sleepiness, despite up to 12 hrs./night of sleep FGradual onset FUsually appears before age 25 FRecurrent hypersomnia - Kleine Levin Syndrome FMay be due to depression

25. Narcolepsy FImmune mediated destruction of hypocretin secreting neurons in the pineal gland FNot related to melatonin FInherited on multiple genes, dominant with incomplete penetrance FCSF levels of hypocretin is low and is a useful test FImmune mediated destruction of hypocretin secreting neurons in the pineal gland FNot related to melatonin FInherited on multiple genes, dominant with incomplete penetrance FCSF levels of hypocretin is low and is a useful test

26. FThe normal physiologic components of REM sleep, dreaming and muscle tone are separated and can occur while the patient is awake, resulting in half sleep dreams, cataplexy and sleep paralysis

27. FCharacterized by attacks of disabling daytime drowsiness and low alertness FShort sleep latency and sleep often begins with REM activity F2/3 of cases are associated with cataplexy, triggered by strong emotion FCharacterized by attacks of disabling daytime drowsiness and low alertness FShort sleep latency and sleep often begins with REM activity F2/3 of cases are associated with cataplexy, triggered by strong emotion

28. Parasomnias FDisoriented Arousal FSleepwalking FNight/Sleep Terrors FHypnagogic Hallucinations FSleep Paralysis FNocturnal Seizures FDisoriented Arousal FSleepwalking FNight/Sleep Terrors FHypnagogic Hallucinations FSleep Paralysis FNocturnal Seizures

29. Parasomnias, continued FREM Behavioral Disorder FBruxism FRhythmic Movement Disorder FRestless Legs Syndrome FREM Behavioral Disorder FBruxism FRhythmic Movement Disorder FRestless Legs Syndrome

30. Sleep History FTiming of insomnia FSleep schedule FSleep environment FSleep habits FSymptoms of other sleep disorders FDaytime effects FMedications, caffeine FLife stressors and worry over insomnia FTiming of insomnia FSleep schedule FSleep environment FSleep habits FSymptoms of other sleep disorders FDaytime effects FMedications, caffeine FLife stressors and worry over insomnia

31. Medications that may cause insomnia FClonidine FBeta Blockers FTheophyline FCertain Antidepressants FProtriptyline, Fluoxetine FDecongestants FStimulants FAlcohol FClonidine FBeta Blockers FTheophyline FCertain Antidepressants FProtriptyline, Fluoxetine FDecongestants FStimulants FAlcohol

32. FExercise in morning or early afternoon lessens insomnia FExercise close to bedtime worsens insomnia FExercise in morning or early afternoon lessens insomnia FExercise close to bedtime worsens insomnia

33. Physical Exam FAnatomic features of obstructive sleep apnea FNeurologic exam in case of restless leg or other neurologic syndrome FAnatomic features of obstructive sleep apnea FNeurologic exam in case of restless leg or other neurologic syndrome

34. Sleep Log FMaintain for 2-4 weeks FSleep and wake times FAwakenings FDaytime naps and activities FCorrelation with bed partner FMaintain for 2-4 weeks FSleep and wake times FAwakenings FDaytime naps and activities FCorrelation with bed partner

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38. Nonpharmacalogic Therapy FCognitive Behavioral Therapy FIndividual counseling- 6 sessions FEffective in 50% of patients FCognitive Behavioral Therapy FIndividual counseling- 6 sessions FEffective in 50% of patients

39. Relaxation Therapy FRecognize and control tension through systematically tensing and relaxing various muscle groups FGuided imagery and meditation FBiofeedback FRecognize and control tension through systematically tensing and relaxing various muscle groups FGuided imagery and meditation FBiofeedback

40. Stimulus Control Therapy FReassociate the bed with sleepiness rather than wakefulness FNo reading, TV, eating or working in bed FLying down only when sleepy FIf unable to sleep after 15-20 minutes, get out of bed and do something else FReassociate the bed with sleepiness rather than wakefulness FNo reading, TV, eating or working in bed FLying down only when sleepy FIf unable to sleep after 15-20 minutes, get out of bed and do something else

41. Sleep-restriction Therapy FEliminate excess time in bed awake FPurposefully limit sleep, which leads to more efficient and effective sleep habits. FGradually allow more time in bed as insomnia resolves FEliminate excess time in bed awake FPurposefully limit sleep, which leads to more efficient and effective sleep habits. FGradually allow more time in bed as insomnia resolves

42. Pharmacologic Therapy FNon-prescription FPrescription FNon-prescription FPrescription

43. Non-prescription Therapy FValerian - An herbal medication that may be safe and effective to decrease sleep latency. May work better if taken regularly at night rather than PRN. FMain risk is uncontrolled manufacturing of herbal compounds FValerian - An herbal medication that may be safe and effective to decrease sleep latency. May work better if taken regularly at night rather than PRN. FMain risk is uncontrolled manufacturing of herbal compounds

44. Melatonin FA natural hormone produced in the pineal gland FCircadian rhythm increases the blood level at night, especially when it is dark FAntioxidant properties FMay be effective FA natural hormone produced in the pineal gland FCircadian rhythm increases the blood level at night, especially when it is dark FAntioxidant properties FMay be effective

45. What is the active ingredient in Tylenol PM?

46. Diphenhydramine hydrochloride FMain Ingredient in Tylenol PM, Sominex, Unisom, etc. FAntihistamine and anticholinergic agent FNon-specific and long lasting FMain Ingredient in Tylenol PM, Sominex, Unisom, etc. FAntihistamine and anticholinergic agent FNon-specific and long lasting

47. Prescription Drugs FBenzodiazepines - most common FIf the problem is falling asleep, use medication with a rapid onset of action FVery short 1/2 life may be associated with increased risk of rebound anxiety FIf the problem is staying asleep, a hypnotic with a slower rate of elimination may be more useful FBenzodiazepines - most common FIf the problem is falling asleep, use medication with a rapid onset of action FVery short 1/2 life may be associated with increased risk of rebound anxiety FIf the problem is staying asleep, a hypnotic with a slower rate of elimination may be more useful

48. Rapid Onset Drugs Slow Elimination Drugs Zoldipem (Ambien) Temazepam (Restoril) Zaleplon (Sonata) Estazolam (Prosom) Triazolam (Halcion) Flurazepam (Dalmane)

49. Concomitant Depression FAntidepressants with sedative properties FTrazodone (Desyrel) FAmitriptyline (Elavil) FAntidepressants with sedative properties FTrazodone (Desyrel) FAmitriptyline (Elavil)

50. Eszopiclone (Lunesta) FNew class of non- benzodiazepine FMay affect GABA receptor FRapid onset, medium 1/2 life FNo tolerance or withdrawal after 6 months of treatment F1,2,3 mg. dose FNew class of non- benzodiazepine FMay affect GABA receptor FRapid onset, medium 1/2 life FNo tolerance or withdrawal after 6 months of treatment F1,2,3 mg. dose

51. Rozerem (ramelteon) FUnscheduled prescription drug FActs on Melatonin receptors FNo activity on the following receptors FGABA, neuropeptides, cytokines,seratonin, dopamine, noradrenaline, acetylcholine, or opioid FUnscheduled prescription drug FActs on Melatonin receptors FNo activity on the following receptors FGABA, neuropeptides, cytokines,seratonin, dopamine, noradrenaline, acetylcholine, or opioid

52. Rozerem, continued FGiven to 14 subjects with history of abuse of sedative/hypnotics or anxiolitics; Result: no potential for abuse FDosage-8 mg. (not with or immediately following a high fat meal FGiven to 14 subjects with history of abuse of sedative/hypnotics or anxiolitics; Result: no potential for abuse FDosage-8 mg. (not with or immediately following a high fat meal

53. Sedative-hypnotic Medication General rules FSymptomatic relief, not a cure FCombine with nonpharmacologic treatment FSmallest effective dose for the shortest possible time FAvoid alcohol FPregnancy is a contraindication FTaper off to avoid rebound insomnia FSymptomatic relief, not a cure FCombine with nonpharmacologic treatment FSmallest effective dose for the shortest possible time FAvoid alcohol FPregnancy is a contraindication FTaper off to avoid rebound insomnia

54. The End