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INSOMNIA

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Nonrestorative sleep persisting for at least 1 month ... 49% of adults surveyed were dissatified with their sleep 5 nights per month ... – PowerPoint PPT presentation

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Title: INSOMNIA


1
INSOMNIA
  • Jeffrey Lin, M.D.
  • Fellow, Sleep Medicine
  • Stanford University Medical Center
  • December 3, 2008

2
DISCLOSURES
  • None
  • Special thanks to
  • Dr. Philip Becker
  • Dr. David Neubauer
  • Dr. Edward Stepanski.

3
OBJECTIVE
  • Pathogenesis
  • Prevalence
  • Impact
  • Pharmacologic treatment
  • Cognitive-behavioral therapy

4
PHYSIOLOGY OF SLEEP
www.ge.infn.it/rita/fisio20sonno_ing.htm
5
www.douglasrecherche.qc.ca
6
PHYSIOLOGY OF SLEEP
7
DEFINITION OF INSOMNIA
  • NHLBI Subjective patient complaint of difficulty
    falling asleep, difficulty staying asleep, poor
    quality sleep, or inadequate sleep despite
    adequate opportunity.
  • DSM-IV definition
  • Difficulty initiating or maintaining sleep for at
    least 1 month
  • Nonrestorative sleep persisting for at least 1
    month
  • Accompanied by clinically significant impairment
    in daytime functioning
  • Research criteria
  • Sleep latency 30 minutes
  • Sleep efficiency
  • Sleep disturbance 3 times per week

NHLBI working group on Insomnia. Bethesda, Md
NHLBI 1998. NIH Publication 98-4088 Ringdahl EN
et al. J Am Board Fam Pract. 2004 17212-219
8
SLEEP PATTERNS IN INSOMNIA
  • Sleep onset insomnia
  • Difficulty falling asleep
  • Longer time to sleep onset
  • Sleep maintenance insomnia
  • Difficulty staying asleep
  • Frequent nocturnal awakenings
  • Sleep offset insomnia
  • Waking too early in the morning
  • Nonrestorative sleep
  • Fatigue despite adequate sleep duration

DSM-IV-TR. 4th ed. 2000597-661 Czeisler CA et
al. Harrisons Principles of Internal Medicine
15th ed. 2001 155-163
9
DURATION OF INSOMNIA
  • Transient insomnia episodic
  • Acute illness
  • Jet lag
  • Shift change
  • Short-term insomnia few days to 3 weeks
  • Major life event
  • Substance abuse
  • Chronic insomnia longer than 3 weeks
  • Chronic illness
  • Psychiatric illness

NHLBI working group on Insomnia. Bethesda, Md
NHLBI 1998. NIH Publication 98-4088
10
EPIDEMIOLOGY OF INSOMNIA
  • 30-50 of American adults experience insomnia
    during a 1 year period
  • Prevalence of chronic/severe insomnia is 10
  • 49 of adults surveyed were dissatified with
    their sleep 5 nights per month
  • 50 of patients presenting to primary care
    physicians experience insomnia

NHLBI working group on Insomnia. Bethesda, Md
NHLBI 1998. NIH Publication 98-4088 Smith MT, et
al. Am J psychiatry. 2002 1595-11 Hajak G et
al. Eur Psychiatry. 2003 18201-8 Ringdahl EN et
al. J Am Board Fam Pract. 2004 17212-219
11
WOMEN AND INSOMNIA
  • Women are at greater risk for insomnia than men
  • Influenced by hormonal cycles
  • The menstrual cycle
  • 36 during menstruation
  • 14 during late luteal phase
  • During and after pregnancy
  • During the peri/postmenopausal period

Miller EH. Clin Cornerstone. 20046(Suppl
1B)s8-s18 Katz DA, McHorney CA. J Family Pract.
200351229-235 Krystal AD. Clin Cornerstone.
20046(Suppl 1B)s19-s28 Shaver JLF. Nurs Clin N
Am. 20237707-718
12
AGE AND INSOMNIA
  • Age-related changes in sleep architecture
  • Increased in light/transitional sleep
  • Reduction in slow-wave sleep
  • Decline in overall sleep time
  • Comorbid illness
  • Age-related illnesses
  • Side effects of medications
  • Primary sleep disorders
  • Social factors
  • Bereavement
  • Sleep patterns altered by retirement

Ringhahl EN, Peireira SL, Delzell JJ. Am Board
Fam Pract. 200417212-219
13
PRIMARY VS. COMORBID INSOMNIA
  • Primary insomnia
  • Sleep disturbance that can not be explained by
    any underlying medical, psychiatric, or
    environmental problem
  • Sleep disturbance that persists after the
    resolution of the original trigger
  • Comorbid insomnia
  • Sleep disturbance is comorbid with an underlying
    problem

14
CAUSES OF COMORBID INSOMNIA
www.sleepreviewmag.com/.../2004-05_04.
15
DIAGNOSES ASSOCAIATED WITH CHRONIC INSOMNIA
Coleman et al. JAMA 1982
16
CONTRIBUTING FACTORS TO DEVELOPMENT OF INSOMNIA
  • Predisposing factors
  • Personality
  • Sleep-wake cycle
  • Circadian rhythm
  • Coping mechanisms
  • Age
  • Precipitating factors
  • Situational
  • Environmental
  • Medical
  • Psychiatric
  • Medications
  • Perpetuating factors
  • Conditioning
  • Substance abuse
  • Performance anxiety
  • Poor sleep hygiene

Hauri PJ. Clin chest med. 1998
19157-168 Spielman AJ et al. Psychiatr Clin
North Am. 1987 10541-553
17
COGNITIVE BEHAVIORAL MODEL OF INSOMNIA
  • Dysfunctional Cognition
  • Worry over sleep loss
  • Rumination over consequences
  • Unrealistic expectations
  • Misattributions/ amplifications
  • Arousal
  • Emotional
  • Cognitive
  • Physiologic
  • Consequences
  • Mood Disturbances
  • Fatigue
  • Performance impairments
  • Social discomfort
  • Maladaptive Habits
  • Excessive time in bed
  • Irregular sleep schedule
  • Daytime napping
  • Sleep-incompatible activities

Morin CM. Insomnia Psychological Assessment and
Management. New York, NY Guilford 1993
18
CONSEQUENCES OF INSOMNIA
  • Worsens psychiatric disorders
  • Prolongs medical illnesses
  • Reduced quality of life
  • Higher absenteeism
  • Increased accident risk
  • Higher health care costs
  • Cognitive impairment

Benca RM. J Clin Psychiatry. 200162(suppl
10)33-38
19
DEPRESSION AND INSOMNIA
  • Insomnia is both a risk factor for depression and
    a consequence of depression
  • Could effective management of insomnia decrease
    the incidence of depression?
  • Could effective management of insomnia modify the
    risk for relapsing depression?

LustbergL, Reynolds CF. Sleep Med Rev.
20003253-262
20
  • Katz, D. A. et al. Arch Intern Med
    19981581099-1107.

21
CAR ACCIDENTS AND SLEEP DISORDERS
Powell NB et al. Otolaryngol Head Neck Surg.
2002 126217-227
22
ECONOMIC IMPACT OF INSOMNIA
  • Direct Cost
  • Drugs 1.97 Billion (41 prescription)
  • Services 11.96 Billion
  • Indirect Costs
  • Decreased productivity
  • Higher accident rate
  • Increased absenteeism
  • Increased comorbidity
  • Total Annual Cost 30-107 billion

Walsh JK, Engelhardt CL. Sleep. 199922(suppl
2)S386-393 Stoller MK. Clin Ther.
199416873-879 Chilcott LA, Shapiro CM.
Pharmacoeconomics. 199610(suppl 1)1-14
23
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24
PHARMACOLOGIC TREATMENT
  • Historic trials
  • Fermented beverages
  • Plant preparations
  • Laudanum (opium/alcohol)
  • Chloral hydrate
  • Barbiturates
  • Current trials
  • Antihistamines
  • Benzodiazepine hypnotics
  • Nonbenzodiazepine hypnotics
  • Selective melatonin receptor agonist
  • Investigational compounds

25
MOST COMMONLY USED DRUGS FOR INSOMNIA
  • Trazodone
  • Zolpidem
  • Amitriptyline
  • Mirtazapine
  • Temazepam
  • Quetiapine
  • Zaleplon
  • Clonazepam
  • Hydroxyzine
  • Alprazolam
  • Lorazepam
  • Olanzapine
  • Flurazepam
  • Doxepin
  • Cyclobenzaprine
  • Diphenhydramine

Walsh et al, 2005
26
CURRENT FDA-APPROVED INSOMNIA TREATMENT MEDS
  • Benzodiazepine receptor agonists
  • Benzodiazepine hypnotics
  • Temazepam (Restoril)
  • Flurazepam (Dalmane)
  • Nonbenzodiazepine hypnotics
  • Zolpidem (Ambien)
  • Zaleplon (Sonata)
  • Selective melatonin receptor agonist
  • Ramelteon (Rozerem)

27
BENZODIAZEPINE RECEPTOR AGONISTS
  • Gamma aminobutyric acid (GABA)
  • Predominate inhibitory neurotransmitter in CNS
  • A primary inhibitory neurotransmitter in the
    ventrolateral preoptic nucleus (VLPO)
  • GABAa receptor complex
  • Pentameric structure
  • Modulates chloride ion channel
  • Hyperpolarizes neurons

28
GABA RECEPTOR COMPLEX
29
BENZODIAZEPINE RECEPTOR AGONISTS
  • Bind to the bezodiazepine receptor site
  • Enhances GABA activation of chloride ion channel
  • Promote sleep by sedating effect
  • Absorption allows rapid sleep onset
  • Eliminated half-life and dose determines the
    duration of action
  • Immediate and controlled-release formulations

30
HYPNOTICS IN THE US
31
HYPNOTICS IN THE US
32
BZRA PRESCRIBING GUIDELINES
  • Bedtime dosing
  • Avoid hazardous activities after dose
  • Allow sufficient time in bed
  • Dose adjustments
  • Elderly and debilitated patients
  • Hepatic impairment
  • Nightly vs. as needed dosing
  • Middle of the night dosing?
  • Taper dose on discontinuation?

33
BZRA ADVERSE EFFECTS
  • Residual effects
  • Dizziness
  • Headache
  • Somnolence
  • Blurred vision
  • Nausea/diarrhea
  • Fatigue
  • Ataxia
  • Anterograde amnesia
  • Sonambulism/complex sleep behavior

34
BZRA DISCONTINUATION EFFECTS
  • Rebound insomnia sleep worsened relative to
    baseline for 1-2 days
  • Recrudescence return of original insomnia
    symptoms
  • Withdrawal new cluster of symptoms not present
    prior to treatment

35
SELECTIVE MELATONIN RECEPTOR AGONIST
  • Ramelteon (Rozerem)
  • MT1 attenuation of circadian alerting signal
  • MT2 circadian phase reinforcement or shifting
  • Acts on the suprachiasmatic nucleus
  • Influences the circadian rhythm effects on the
    sleep-wake cycle
  • No abuse liability, not a DEA controlled substance

36
SELECTIVE MELATONIN RECEPTOR AGONIST
  • FDA approved for sleep onset insomnia
  • No limitation on duration of use
  • Non-sedating
  • Single dose 8 mg
  • Take about 30 minutes prior to bedtime
  • Half-life 1-2.6 hrs

37
SELECTIVE MELATONIN RECEPTOR AGONIST
  • Adverse events
  • Somnolence
  • Dizziness
  • Fatigue
  • Avoid with hepatic impairment

38
FIRST GENERATION ANTIHISTAMINE
  • Postsynaptic histaminic and muscarinic blockade
  • Diphenhydramine
  • Regulated by the FDA
  • Half-life 8 hrs
  • Rapid tolerance to sedating effects
  • Pill strengths (mg) 25, 37.5, 50

39
FIRST GENERATION ANTIHISTAMINE
  • Potential adverse effects
  • Residual effects
  • Delirium
  • Dry mouth
  • Constipation
  • Blurred vision
  • Urinary retention
  • Narrow angle glaucoma exacerbation

40
DIETARY SUPPLEMENTS
  • Not FDA regulated
  • Valerian
  • Kava-Kava
  • Melatonin
  • Passion flower
  • Skullcap
  • Lavender
  • Hops

41
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42
COGNITIVE-BEHAVIORAL TREATMENT FOR INSOMNIA
  • Indications
  • Primary Insomnia
  • Psychophysiological Insomnia
  • Inadequate Sleep Hygiene
  • Comorbid Insomnia
  • With a medical condition
  • With a mental disorder
  • Important to combine both cognitive and
    behavioral components

43
CBT FOR COMORBID INSOMNIA
44
EFFICACY OF CBT FOR INSOMNIA
45
EFFICACY OF CBT FOR INSOMNIA
46
BEHAVIORAL TREATMENTS
  • Sleep hygiene education
  • Specific behaviors will directly interfere with
    the ability to sleep
  • The behaviors can be changed with education
  • No sufficient as a stand alone treatment
  • Sleep restriction therapy
  • Increased propensity to sleep by increasing
    homeostatic sleep drive with partial sleep
    deprivation
  • Systematic reduction of time in bed to the amount
    of total sleep time from sleep log data
  • Increase time in bed by 15 minutes only when
    sleep efficiency exceeds 90 for 5 nights

47
BEHAVIORAL TREATMENTS
  • Stimulus control therapy
  • Assumes that there is a learned associated
    between wakefulness and the bedroom
  • To break the cycle, the patient must not spend
    time wide awake in the bedroom
  • Go to bed only when sleepy
  • Do not use the bedroom for sleep-incompatible
    activities
  • Leave the bedroom if awake for more than 20
    minutes
  • Return to bed only when sleepy
  • Do not nap during the day
  • Arise at the same time every morning

48
BEHAVIORAL TREATMENTS
  • Relaxation training
  • Progressive muscle relaxation
  • Guided Imagery
  • Biofeedback
  • Self-hypnosis

49
COGNITIVE THERAPY
  • Cognitive restructuring
  • Rational-Emotive therapy
  • Specific techniques for rumination
  • Thought-stopping
  • Meditation techniques

50
COGNITIVE THERAPY
  • Five domains of cognitive activity hypothesized
    to contribute to insomnia
  • Worry and rumination
  • Attentional bias and monitoring for sleep-related
    threat
  • Unhelpful beliefs about sleep
  • Misperception of sleep and daytime deficits
  • The use of safety behaviors that maintain
    unhelpful beliefs

51
OBJECTIVE
  • Pathogenesis
  • Prevalence
  • Impact
  • Pharmacologic treatment
  • Cognitive-behavioral therapy

52
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