Sleep in the Elderly

Richard P. Millman, MDJuly 15, 2009

Development of SleepDevelopment of Sleep

Roffwarg HP, Muzio JN and Dement WC. Science 1966.

Common Sleep Disorders in the Elderly

• Insomnia2. Circadian Rhythm Issues3. Restless Leg Syndrome4. Obstructive Sleep Apnea5. REM Sleep Behavior Disorder

Definition of Insomnia

Not a diagnosis, but a clinical problempresenting as one or more of the following:

n

Difficulty falling asleepn

Difficulty maintaining sleepn

Patient’s perception of poor sleep qualityResulting inn

Daytime sleepiness or fatiguen

Impaired function

Erman MK, Psychiatr Clin North Am. 1987;10:525-539Naylor MW, Aldrich Ms, In: Kryger MH, et al, eds. Principles and Practice of Sleep Medicine, 1994:413-417The Gallup Survey. Sleep in America. The Gallup Organization; 1991:1-50.

Ancoli-Israel1999

Prevalence of Insomnia* in theGeneral Adult PopulationPrevalence of Insomnia* in theGeneral Adult Population

10.2

17.716.8

9

11.7

10

0

5

10

15

20

Perc

ent

Ford1989

Ohayon1998

Ohayon2001

Ishigooka1999

Simon1997

*Insomnia = sleep disturbance every night for two weeks or more, or similarly stringent criteria.• Ford DE, Kamerow DB. JAMA. 1989;262:1479-1484.• Ohayon MM, et al. Compr Psychiatry. 1998;39:185-197.• Ohayon MM, Roth T. J Psychosom Res. 2001;51:745-755.• Ancoli-Israel S, Roth T. Sleep. 1999;22(suppl 2):S347-S353. • Ishigooka J, et al. Psychiatry Clin Neurosci. 1999;53:515-522.• Simon GE, VonKorff M. Am J Psychiatry. 1997;154:1417-1423.

Insomnia in Patients WithChronic Medical ConditionsInsomnia in Patients WithChronic Medical Conditions

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60Pe

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Diabetes

MI

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Severe Insomnia†

Insomnia*

*Sleep disturbance “some” or “a good bit” of the time for four weeks.†Sleep disturbance “most” or “all” of the time for four weeks.MI = myocardial infarction; CHF = congestive heart failure; BPH = benign prostatic hyperplasia.Katz DA, McHorney CA. Arch Intern Med. 1998;158:1099-1107.

Chronic insomnia is associated with poorer

physical and emotional health

Sleep Disturbance Precedes the Onset of Depression

• Insomnia or difficulty sleeping under stress increased risk for depression later in life

- Johns Hopkins Precursors Study; Chang, 1997

• Insomnia predicted depression in elderly populations

- Dryman and Eaton, 1991; Livingston, 1993

• Precedes dysphoria, dissatisfaction, crying and irritability

- Perlis ML et al. J Affect Disord. 1997;42:209

Sleep Disturbance Precedes the Onset of Psychiatric Illness in General Adult Population

• Odds of developing depression during a year of insomnia - 39.8

• If insomnia resolved during the year - 1.6

Ford and Ford and KamerowKamerow.. JAMAJAMA. 1989;262:1479. 1989;262:1479--1484.1484.

Causes of Insomnia

PharmacologicAlcohol MAO inhibitorsAnticancer agents NicotineAntihypertensives SteroidsAutonomic agents TheophyllineCaffeine Thyroid preparationsCNS depressantsCNS stimulants

CNS - central nervous system; MAO - monoamine oxideAdapted from Erman MK. Hosp Proct. 1989, 23 (suppl 2):11: and Beaumont G. 1990

Diagnosing Insomnia: DifferentialDiagnosing Insomnia: DifferentialDiagnosisDiagnosis

Hauri PJ. Clin Chest Med. 1998;19:157-168.

Medical Etiologies

Cardiac diseasePulmonary diseasePain secondary to a medical condition (eg, cancer)Neurologic degenerativedisordersAllergies/asthmaRestless leg syndromeSleep apnea

Psychiatric Etiologies

Mood disordersAnxiety disordersSubstance abuse

disorders

Other Etiologies

Primary insomniaCircadian rhythm disorders

Types of Insomnia: DurationTransient Insomnia

Several daysShort-term Insomnia

< 3 weeks

Chronic Insomnia

> 3 weeks

1 week 2 weeks 3 weeks

NIH Consensus Conference. JAMA. 1984:251:2410-2414

CASE

“I wake up every hour to go to the bathroom.”

Sleep Hygiene Educationi Maintain a regular schedule for going to bed

and arisingi Avoid excessive time in bedi Avoid taking naps during the day and early eveningi Use the bed only for sleeping and sexual relationsi Do not watch the clock while in bedi Do something relaxing before bedtime

Zarcone VP, JR In: Kryger MH. Et al, eds. Principles and Practice of Sleep Medicine2nd ed. 1994 542-546 Becker et al. Postgrad Med 1993, 66-85

Sleep Hygiene Education (cont’d)iMake the bedroom as quiet and comfortable as

possibleiAvoid taking the troubles of the day to bediAvoid consumption of alcohol or caffeinated

beverages, especially within 6 hours of bedtimeiGet exercise, but early in the day (not within 2

hours of bedtime)

iAvoid going to bed hungry - eat a light snack in the evening if necessary

Zarcone VP, JR In: Kryger MH. Et al, eds. Principles and Practice of Sleep Medicine2nd ed. 1994 542-546 Becker et al. Postgrad Med 1993, 66-85

Increase Activity During the Daytime

Sleep Restriction

nRestrict time in bed (TIB) to actual sleep timen

Establish TIB based on sleep efficiency (SE) averaged over a 5 day period

n

Increased TIB by 15 minutes if average SE over 5 days >90% (85% for elderly); decrease if SE <85% (80% for elderly)

n

Be aware that daytime sleepiness is a potential side effect

Spielman AJ, et al. Psychiatr Clin North Am 1987;10:541-553Spielman AJ, et al. Sleep 1987;10:45-56.

Characteristics of the Ideal Hypnotic

No effect on memory

No respiratory depression

No interactionwith ethanol

No tolerance

No physicaldependence

IdealHypnotic

Rapidabsorption

No reboundinsomnia

No residualeffects

Mechanism otherthan generalCNS depression

Rapid sleep induction

Induction of physiologicalsleep pattern

Optimal half-life

No formationof activemetabolites

Barthollini G In: Sauvanet JP, et al, eds. Imidazopynidines in Sleep Disorders 1988: 1-9

NIH Statements About Agents Not Approved for Insomnia Treatment

• Dietary supplements/herbal remedies– Valerian: Limited evidence shows no benefit beyond placebo– No systematic evidence for efficacy; there are significant concerns about

risks• Antihistamines• Melatonin

– Little evidence exists for efficacy in the treatment of insomnia• Antipsychotics

– Studies demonstrating the usefulness…are lacking; use in chronic insomnia is not recommended

• Antidepressants– All antidepressants have potentially significant adverse effects, raising

concerns about the risk-benefit ratio.

Approved Pharmacologic Treatment Options for Insomnia

• BZDs– Estazolam– Flurazepam– Quazepam– Temazepam– Triazolam

• Non-BZD agents affecting GABA/BZD complex– Eszopiclone– Zaleplon– Zolpidem – Zolpidem CR

• MT receptor agonist– Ramelteon

GABA Reuptake

Usual Half-Life Range of BenzodiazepineTriazolam 1.5 - 5.5 hTemazepam 8 - 20.0 hEstazolam* 20 - 30.0 hQuazepam* 15 h + 35.0 hFlurazepam* 36 h +

FlurazepamQuazepam

Estazolam

Temazepam

Triazolam

O 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100Half-Life (h)

*Includes active metabolitesGreenblatt DJ, Shader RI, In: Meltzer HY, ed. Psychopharmacology: The Third GenerationThe Medical Letter. October 4, 1991;33(854): 91.

Table 9:1. Relative Risk of Hip Fracture

Long-acting Relative Short-acting RelativeBenzodiazepines Risk Benzodiazepines Risk

Chlordiazepoxide 2.3 Oxazepam 1.4Flurazepam 1.9 Lorazepam 1.0Diazepam 1.5 Triazolam 1.0Overall 1.7 Overall 1.1

Adapted from JAMA 1989;262:3303-3307

Effect of Drugs on Sleep Architecture

Polysomnographic Findings†

Barbiturates,Nonbarbiturates Benzodiazepines Zolpidem

♦

Stage 1 sleep♦

Stage 2 sleep♦

Stages 3 & 4 sleep ♦

REM sleepLatency *Time in *Number of cycles *

♦

Total sleep time /

† Clinical significance unknown* Not consistent among benzodiazepines

= No significant effects

Ashton H. In Cooper R, ed. Sleep London: Chapman & Hall Medical; 1994:175-211.

Hobbs WR, et al. In Hardman JG, et al. Eds. Goodman & Gilman’sThe Pharmacological Basis of Therapeutics, 9th ed., 1996:361-396

Bartholini G. In Sauvanet JP, et al. Eds. Imidazopyridines in Sleep Disorders. 1988:1-9.

Mariott L et al. J Clin Psychopharmacol 1989;9:9-14.I

Proposed Specificity of ActionDifferences in pharmacologic response between drugs may be due to drug selectivity for GABAA receptor subtypes

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Animal Models

Hypnotic

Antico

nvuls

ant

Myorelaxant

Anticonvulsant

Myorel

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Hypnotic

Zolpidem (mg/kg) Triazolam (mg/kg)

Adapted from Sanger DJ, Zivkovic B. Psychopharmacology. 1966: 89:317-322

CASE

“I cannot fall asleep until 2 A.M. and I am always late forappointments.”

Delayed and Advanced Sleep Phase Syndromes

Diagnostic Criteria for RLS

• A desire to move the limbs usually associated with paresthesias or dysesthesias

• Motor restlessness during wakefulness• Symptoms are worse at rest and are

alleviated with activity • Symptoms are worse in the evening or night

International RLS study Group 1995

Pharmacological Treatment of RLS

Dopaminergic Agentslevodopa/carbidopapergolidepramipexoleropinirole

Opiodshydrocodonepropoxyphene