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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
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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
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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
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How Much do we sleep?
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Sleep stages
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Sleep is Cyclical – 90 min
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“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
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Classification of Sleep Disorders
Disorders of Excessive Sleepiness (DOES)
Disorders of Initiating and Maintaining Sleep (DIMS)
Parasomnias
Disorders of circadian rhythm
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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.
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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
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Epidemiology
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Sleep Problems- prevalence
Insomnia is the most common sleep disorder,prevalence of 10 to 15%
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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
20
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
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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
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Pathophysiology
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Schematic representation of the gamma-aminobutyric acid (GABAA)-benzodiazepine (BDZ)
receptor complex.
Am J Psychiatr 1991;48:162-173. Copyright 1991
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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.
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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
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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.
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• 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
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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
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Medications Commonly Used for Insomnia
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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.
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How to treat?
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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
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What would you recommend for treatment?
55 year-old woman with primary insomnia and difficulty initiating sleep
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Cognitive Behavior Therapyand Pharmacotherapy for Insomnia
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Arch Intern Med. 2004;164:1888-1896
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What would you recommend for treatment?
63 year-old man with COPD CHF complains of repeated awakenings throughout the night
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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 +
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Improved Sleep Efficiency in People with a Secondary Sleep Disorder
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What would you recommend for treatment?
65 year-old woman with insomnia , ask your help to stop BZD treatment
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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
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Thanks
Clinic: Yigal Alon 29, Haifa, Ramat Yam 12, Herzelia, 04-8268826 www.navehmed.com