Insomnia Update

Naveh Tov MD PhDInternal Pulmonary Sleep medicine

Bnai-Zion Medical Center

Clinic: Yigal Alon 29, Haifa, Ramat Yam 12, Herzelia, 04-8268826 www.navehmed.com

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Presentation Overview

1. Sleep introduction2. Insomnia

a. Definition b. Epidemiology c. Pathophysiologyd. Treatment e. How to treatf. Summary

Sleep definition

Sleep is defined as a sustained quiescent period, spent in a species-specific characteristic, posture or site, and during which the threshold for response to stimuli is raised, although a stimulus of sufficient strength will rapidly reverse the state.

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• Reduced awareness of and interaction with the external environmen

2• Reduced motility and muscular activity

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• Partial or complete cessation of voluntary behavior and self-consciousne

Why Do We Sleep?

ESSENTIAL TO OVERALL HEALTH &

WELL-BEING

Key to our health,

performance, safety

Essential to perform

cognitive & physical tasks

Key to our quality of life

Essential component

such as nutrition &

exercise

How Much do we sleep?

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Sleep stages

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Sleep is Cyclical – 90 min

“Opponent Process” - model of sleep regulation Edgar, J Neurosci, 1993

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Sleep/Wake Neurotransmitters and Modulators: Targets for Pharmacologic Development

Wake Norepinephrine Serotonin Acetylcholine Histamine Orexin/hypocretin

Sleep Adenosine -aminobutyric acid

(GABA) Galanin Melatonin

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Consequences of sleep loss

Classification of Sleep Disorders

Disorders of Excessive Sleepiness (DOES)

Disorders of Initiating and Maintaining Sleep (DIMS)

Parasomnias

Disorders of circadian rhythm

Insomnia

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Insomnia definition

insomnia is defined by difficulties in falling asleep, maintaining sleep,

and early morning awakening, and is coupled with daytime consequences

such as fatigue, attention deficits, and mood instability.

Symptoms

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Insomnia types

short-term (< 3 months duration) chronic (symptoms occur ≥ 3 times/week

for at least 3 months) and not related to inadequate opportunity for sleep or another sleep disorder

Epidemiology

Sleep Problems- prevalence

Insomnia is the most common sleep disorder,prevalence of 10 to 15%

Primary vs Comorbid Insomnia

Ohayon MM. Sleep Med Rev. 2002;6:97-111.

Psychiatric Disorders44%

Primary Insomnia16%

Other Illnesses,

Medications, etc

11%

Other Sleep

Disorders5%

No DSM-IV Diagnosis24%

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20 30 40 50 60 70 800

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40

60

80

Onset Maintenance Combined

Insomnia Prevalence by Age

Lichstein KL et al. In: Epidemiology of Sleep: Age, Gender, and Ethnicity. Mahwah, NJ: Erlbaum; 2004.

Type

)%(

Lower Boundary of Age Decade

Insomnia - Costs Insomnia symptoms

-Overall prevalence 30-48%

-Often or always: 16-21%

-Moderate to extreme: 10-28%

Insomnia symptoms +

daytime consequences

9-15%

Insomnia

diagnosis

6%

Direct economic costs of insomnia in the US ~ $14 billion

Ohayon, Sleep Med Rev, 2002

Pathophysiology

Schematic representation of the gamma-aminobutyric acid (GABAA)-benzodiazepine (BDZ)

receptor complex.

Am J Psychiatr 1991;48:162-173. Copyright 1991

Reduced Brain GABA in Primary Insomnia

Winkelman JW et al. SLEEP 2008;31(11):1499-1506 .

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Predisposing Factors

Not well understood Hypothetical factors

Increased tendency to hyperarousal Increased cortisol, heart rate responsivity,

metabolic rate, catecholamines, EEG Decreased homeostatic sleep drive Prone to

Worry Depression, anxiety

Significant night-type/morning-type Familial vulnerability

EEG = electroencephalogram.

Genes implicated in the neurobiology of insomnia

Lancet Neurol 2015; 14: 547–58

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Precipitating Factors

These factors are the focus of the nosologic system (eg, stress, pain/illness, depression/anxiety, shift work, etc.)

A specific precipitant is often hard to identify with certainty Family (24%)

Marital, child

Physical health (23%) Pain, illness

Work, school (17%) Stress, shift work

Mental health (12%) Depression

Undetermined (22%)

Bastien CH et al. Behav Sleep Med. 2004;2:50-62.

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Perpetuating Factors

Behavioral Irregular sleep-wake schedule Excessive time in bed Excessive caffeine use Stimulating activities close to bedtime, or in the middle of

the night Clock watching during the night

Cognitive Worry throughout the day about sleep Fear of not sleeping Irrational beliefs concerning consequences of poor sleep

Treatment

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Insomnia Treatment

CBT takes longer to help, but the gains are maintained for up to 2 years later

Pharmacologic treatment provides immediate benefit

Others (milder effect than CBT, may improve medication effect): Tai Chi, Chi Gong, Yoga Acupuncture, Acupressure Herbs Hypnosis, meditation

CBT = Cognitive Behavior Therapy.

• Unrealistic sleep expectations

• Misconceptions about sleep

• Sleep anticipatory anxiety

• Poor coping skills

• Excessive time in bed• Irregular sleep

schedules• Sleep incompatible

activities• Hyperarousal

• Inadequate sleep hygiene

Psychological / Behavioral Treatments (Treatment Targets)

CognitiveCognitive Therapy

BehavioralStimulus ControlSleep Restriction

Relaxation

EducationalSleep Hygiene

Education

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Components of Cognitive Behavioral Therapy for Insomnia

Non pharmacological treatments37

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Pharmacologic Therapy

Benzodiazepine – Brotizolam, etc.

Non-Benzodiazepine – Zolpidem,

Antidepressants- Trazadone,Mirtazapine, Amitryptyline , Doxepin,

Melatonin- Meltonin, Circadin, Ramelteon

Antihistamines

Antipsychotics

Miscellaneous- Valerian Diphenhydramine

Medications Commonly Used for Insomnia

Sedative hypnotics in older people with insomnia: risks >>>> benefits

24 studies (involving 2417 participants) Sedative use compared with placebo

Sleep quality improved (effect size 0.14, P < 0.05), Total sleep time increased (mean 25.2 minutes, P < 0.001), Number of night time awakenings decreased (0.63, P < 0.001).

Adverse events were more common with sedatives than with placebo:

adverse cognitive events were 4.78 times more common (95% confidence interval 1.47 to 15.47, P < 0.01);

adverse psychomotor events were 2.61times more common (1.12 to 6.09, P > 0.05),

daytime fatigue were 3.82 times more common (1.88 to 7.80, P < 0.001) BMJ 2005

In people over 60, the benefits of these drugs may not justify the increased risk, particularly if the patient has additional risk factors for cognitive or psychomotoradverse events.

How to treat?

Suggested Treatment in Insomnia

Transient Recurring Chronic

GoodSleeper

• Hypnotic • Hypnotic• CBT

• CBT• Hypnotics

PoorSleeper

• CBT• Considerhypnotic

• CBT • Consider

hypnotic

• CBT• Consider

hypnotic

CBT, cognitive behavioral therapyHypnotics – Circadin, Antidepressant , Z-drugs, BZD

What would you recommend for treatment?

55 year-old woman with primary insomnia and difficulty initiating sleep

Cognitive Behavior Therapyand Pharmacotherapy for Insomnia

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Arch Intern Med. 2004;164:1888-1896

What would you recommend for treatment?

63 year-old man with COPD CHF complains of repeated awakenings throughout the night

1. Medicina (B Aires) 1996;56(5 Pt. 1):472–8.2. Drug Saf 1992;7(2):152–8.3. Respiration 1988;54(4):235–404. Int Clin Psychopharmacol 1990;5(Suppl. 2):94-85.5. congress of the American Association for respiratory care 2007 December 6. J Clin Psychiatry 2004;65(6):752–5

Secondary Insomnia suggested treatment Melatonin, Antidepressant

Reff Respiration Sleep Effect Drug

1-3 Vt, Pco2 sens Latency, Arousals - BZD

Apnea SEF +

4 Vt, Pco2 sens Latency, Arousals - Non-BZD

Apnea SEF +

5 No effect Latency - Melatonin

SEF +

6 Unknown - Trazodone

SEF +

Improved Sleep Efficiency in People with a Secondary Sleep Disorder

What would you recommend for treatment?

65 year-old woman with insomnia , ask your help to stop BZD treatment

Benzodiazepine Discontinuation

CBT Circadin Antidepressant

Am J Psychiatry 2004; 161:332–342

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Insomnia Summary

Prolonged insomnia is associated with an increased risk of new-onset major depression.

It may be an independent risk factor for heart disease, hypertension, and diabetes, especially when combined with sleep times of less than 6 hours per night.

Evaluation should include a complete medical and psychiatric history and a detailed assessment of sleep-related behaviors and symptoms.

Cognitive behavioral therapy is the first line therapy for insomnia (setting realistic goals for sleep, limiting time spent in bed, addressing maladaptive beliefs about sleeplessness, practicing relaxation techniques).

In acute insomnia due to a defined precipitant, use of approved hypnotic medications is indicated.

Severe insomnia - long-term use medication should be considered in patients that is unresponsive to other approaches ( benzodiazepine-receptor agonists, low-dose antidepressants, melatonin agonists, or an orexin antagonist

CBT combined with other methods

Thanks

Clinic: Yigal Alon 29, Haifa, Ramat Yam 12, Herzelia, 04-8268826 www.navehmed.com