considerazioni sulla terapia farmacologica per l'insonnia

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  • 1.Treatment Considerations in Pharmacologic Therapy of Insomnia 33 rdAnnual Pacific NW Regional RCSW Conference Spokane, WA 4/24/2006 Richard D. Simon, Jr., MD Kathryn Severyns Dement Sleep Disorders Center Walla Walla, WA Clinical Assistant Professor of Medicine University of Washington

2. NIH Conclusions

  • Insomnia is a major public health problem
  • Little is known about chronic insomnia
  • Efficacy of cognitive behavioral therapy and benzodiazepine receptor agonists in the acute management of chronic insomnia
    • Little evidence to support other therapies
  • Mismatch between potential life-long nature ofinsomnia and the longest clinical trials
  • Substantial private and public research effortis warranted
  • Educational programs are needed

National Institutes of Health Statement Regarding the Treatment of Insomnia.Sleep . 2005;28:1049-1057. 3. Control Animals: Temperatureand Sleep Stages Edgar DM, Dement WC, Fuller CA.J Neurosci.1993;13(3):1065-1079. 4. Experimental Animals: Temperature and Sleep Stages Edgar DM, Dement WC, Fuller CA.J Neurosci.1993;13(3):1065-1079. 5. Biological Clock

  • Increasing alerting influence throughout day
  • Diminishing alerting influence throughout night
  • Zeitgebers
    • Light
      • After temperature minimum: causes phase advance
      • Before temperature minimum: causes phase delay
    • Melatonin
      • Evening dose: phase advance
      • Morning dose: phase delay

Kryger MH, Roth T, Dement WC, eds.Principles and Practice of Sleep Medicine . Philadelphia,Pa: Elsevier Saunders; 2005. 6. Determinants of Sleep

  • Biological Clock
  • Homeostatic Sleep Drive
  • Social/External Factors
  • Intrinsic Illness

Kryger MH, Roth T, Dement WC, eds.Principles and Practice of Sleep Medicine . Philadelphia,Pa: Elsevier Saunders; 2005. 7. 8. 9. 10. 11. Diagnosis of Insomnia

  • Primarily clinical history
  • Look for psychiatric illnesses and intrinsic sleep disorders
    • Depression, anxiety
    • Circadian rhythm, obstructive sleep apnea,restless legs syndrome
  • Sleep Diary
    • Co-investigator
  • Actigraphy
    • May be helpful
  • Polysomnography
    • Usually not needed

Kryger MH, Roth T, Dement WC, eds.Principles and Practice of Sleep Medicine .Philadelphia,Pa: Elsevier Saunders; 2005. 12. Principles of Improving Sleep

  • Maximize homeostatic sleep drive
    • Limit daytime napping
  • Maximize synchrony between biological clock activity and desired sleep/wake schedule
    • Regular sleep/wake schedule, daytime light and physical activity, nighttime dark and inactivity
  • Maximize treatment of medical/psychiatric illnesses
  • Minimize external sleep-disruptive factors and maximize external sleep-inducing factors

Kryger MH, Roth T, Dement WC, eds.Principles and Practice of Sleep Medicine .Philadelphia,Pa: Elsevier Saunders; 2005. 13. Nonpharmacologic Treatmentof Insomnia

  • Sleep Hygiene 1
  • Sleep Restriction 1
  • Stimulus Control 1
  • Cognitive Behavioral Therapy 2
  • Relaxation 2
  • Paradoxical Intention 2

1. Morin CM, Culbert JP, Schwartz SM .Am J Psychiatry.1994;151(8):1172-1180. 2. Murtagh DR, Greenwood KM.J Consult Clin Psychol.1995;63(1):79-89. 14. Principles of Sleep Hygiene

  • Awaken at approximately the same time each day (biological clock)
  • Exposure to bright light during desired daytime hours(biological clock)
  • Limit napping if insomnia is present(maximize homeostatic sleep drive)
  • Limit or eliminate caffeine, nicotine, ethanol (external factors)
  • Go to bed only when sleepy (maximize homeostatic sleep drive)
  • Exercise daily
  • Shut down your day at least 1 hour before bedtime(minimize cognitive arousals)
  • Worry time (minimize cognitive arousals)
  • Comfortable bedroom used only for sleeping(minimize cognitive arousals, stimulus control)

Morin CM.J Clin Psy.2004;65(suppl 16):33-40. 15. Characteristics of an Ideal Hypnotic

  • Rapid absorption
  • No active metabolites
  • Optimal half-life

Adapted from Bartholini G. In: Sauvanet JP, Langer SZ, Morselli PL,eds.Imidazopyridines in Sleep Disorders . 1988:1-9.

  • Rapid sleep induction
  • Physiological sleep pattern
  • Mechanism other than general CNS depression
  • Sleep maintenance
  • Improved Daytime Function
  • No residual sedation
  • No respiratory depression
  • No ethanol interaction
  • No tolerance
  • No physical dependence
  • No rebound insomnia
  • No effect on memory

Ideal Hypnotic Pharmacokinetic Properties Pharmacokinetic Effect Side Effect 16. Pharmacologic Therapy

  • Benzodiazepine receptor agonists
  • Antidepressants
  • Antihistamines
  • Melatonin
    • Melatonin agonist (ramelteon)

17. Benzodiazepine Receptor Agonists: General Statements

  • Efficacious in insomnia
  • Side effects are usually an extensionof desired effects
    • Sedation
    • Amnesia
  • Duration of action about 2 to 3 times T1/2
  • Rebound
  • Addiction
  • Newer designer drugs

Nowell PD, Mazumdar S, Buysse DJ, et al.JAMA . 1997;278(24):2170-2177. 18. Zolpidem: Effect on Sleep Latencyin People With Chronic Insomnia *Significantly different from placebo ( p 0.05). Data on file, Searle. 22. Tolerance *Significantly different from placebo ( p