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Insomnia 2016

Marcy Wasman, Ph.D.Psychologist

Behavioral Sleep Medicine

Disclosures

• I do not have any relevant financial disclosures at this time.

Outline

• Consequences of Insomnia• Etiology & Pathophysiology of Insomnia

• Optimizing Treatment Protocols

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ICSD-3 Definition of Insomnia

Difficulty initiating

sleep

Difficulty maintaining

sleep

Waking uptoo early

Adequate opportunity & circumstances for sleep+

At least 1 form of daytime impairment present

SleepDissatisfaction

Types of InsomniaICSD 3

• Chronic Insomnia Disorder- occurs at least 3X/week

- symptoms present for at least 3 months

• Short-Term Insomnia Disorder- present for less than 3 months

Costs

$100 BILLION per year

Wickwire 2016

Healthcare, Accidents, Workplace

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PREVALENCE OF INSOMNIA

Chronic 9%

Occasional 27%

None 64%

ONE -THIRD OF AMERICANS ARE AFFECTED BY INSOMNIA

106 MILLIONRoth et al. Sleep 1999;22(suppl 2):S354-S358

Chronic Insomnia: A Persistent Problem

• 75% of those diagnosed have it 1 year later

• 62% still have it 5 years later

Morin 2009

Consequencesof

Insomnia

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Allostasis

1. Inadequate & fragmented sleep disrupts diurnal rhythms throughout the body

2. �Restorative qualities of sleep 3. �Pressure to maintain homeostasis

under difficult conditions

����

Wear and tear without sufficient restoration = gradual deterioration

McEwan 2006Chen 2014

Insomnia Phenotypes

Insomnia Phenotypes

Long-sleepingShort-sleeping A (SSI-A) – hi WASOShort-sleeping B (SSI-B) – hi SOL, med WASO

N=96 measures: attention, working memory, q-EEG & HRV• SSI - �parasympathetic (HRV) at SOL, p<.05 • SSI-B – �attention, p</=.05• SSI-B - q-EEG �power spectra (differences? From

between?) pre & post sleep, p</=.05

Conclusion: SSI-B more impaired

Phenotypes

Miller C 2016

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Mortality Risk & Insomnia:Persistent vs Intermittent

StudyN = 1,409Sx of insomnia over 8 year period with 20

year follow-up

Controlled for sedatives, sleep deprivation, sex, age BMI, smoking status, snoring, marital status, heart disease, diabetes, HTN, activity level, CRP level

Parthasarathy S 2015

Parthasarathy S 2015

Baseline

18-20 YearFollow-up

Parthasarathy S 2015

CRP & Insomnia

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Mortality Risk & Insomnia:Persistent vs Intermittent - Results

Persistent Insomnia:• Increased mortality

• Increased CRP levels• Increased mortality assoc with persistent

insomnia even after adjustment for CRP –other factors must link insomnia & mortality

Epigenetic Aging & Women

Women’s Health INITIATIVE:N = 2,078

• Increased biological aging (p= 0.005)• # of insomnia symptoms +correlated with:

acceleration of aging �older T cell & fewer young, naïve T cells

Assoc. with increased morbidity & mortality?Carroll 2016

Sleep, Depression & Suicide

• Insomnia doubles risk of depression• Suicide attempts significantly linked to

high insomnia severity• Sleep, independent of level of depression,

predicted suicidal thoughts & behaviors

Bernert R 2014

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Disrupted sleep

Increasedfood intake

Appetitive hormone disruption

Impaired executive functions;Increased reward sensitivity

Increased negative affect/emotional stress

Increased impulsivity/impaireddecision making

Homeostatic

Cognitive

Emotional

Behavioral

Environmental FactorsLundahl 2015

Empathy in Health Care Workers

• N = 97 health care workers, matched for sociodem factors

• Interpersonal Reactivity Index & Insomnia Severity Index

• ISI > 8 � IRI mean = 20.49ISI < 8 � IRI mean = 10.50 p<0.05

• Conclusion: Empathy decreased with insomnia. May negatively impact patient care.

Krishnamurthy V 2015

Etiology & Pathophysiology of Insomnia

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Imbalance:Arousing & sleep inducing

brain activity

Stressors:Psychosocial/medical

Dysfunctional sleep-related behaviorLearned sleep preventing associations

Worry/rumination

Spielman ADRiemann D et al. Sleep Med Rev 2010

The Dynamics of InsomniaPredisposing Precipitating

Perpetuating

Transition from Acute to Chronic Insomnia

National Initiative for Tracking & Evaluating Sleeplessness (NITES)

• Good sleepers who did not go on to insomnia had �TIB

• Ss who transitioned from acute to chronic insomnia showed �time in bed (sleep extension)

• Conclusions: �TIB may protect against progression from acute to chronic, as well as the initial development of insomnia

Perlis 2016

PsychophysiologicalCognitive Arousal

Circadian Rhythms

Homeostatic SleepDrive

Cortico-Limbic CognitiveAffective Systems

Hypothalamic Sleep-Wake Centers

Brainstem ArousalCenters

INSOMNIA

Physiological Processes Neural Circuits

Activation Impaired Function Deficient Function

Neurobiological Model of Insomnia

Buysse 2011

Sleep-Wake Function In Insomnia

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Neurobiological Model

• Not 1 sleep-wake brain center, but multiple networks and regions

• Partial sleep states possible, not just on or off

• Insufficient deactivation in wake-promoting regions during NREM

• Default Mode Network & Executive Control Network show �glucose metabolism

Buysse 2011Kay 2016

Default Mode Network

• Activates during wake when the mind is in a resting state, not occupied with a specific task

• Thoughts about the self, mind wandering, introspective thinking, emotional memory processing, thoughts about the future, planning, pre-sleep self referential worries

• DMN areas, particularly the precuneus, found to be overactive in pts with insomnia

• EEG measures do not always fit with subjective experience

Cerebral Metabolic Sleep-Wake Differences

• DMN & ECN areas: Posterior Cingulate/Precuneus

Inferior Parietal CortexDorsolateral Prefrontal Cortex

• Insomnia - smaller Wake vs NREM relative glucose metabolism differences than good sleeper controls

Kay 2016

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Hyperarousal & Insomnia

• Hyperarousal response to stress: �reaction to day stress = �sleep during night

• Increased cortisol at bedtime• Increased NE• Increased brain glucose metabolism during

sleep & wake• Increased power in beta on EEG across cortex

during wake

Hyperarousal in insomnia = 24 hour problemColombo 2016Vgontzas 2001Roehrs 2011Nofzinger 2004Morin 2003

Sleep System Sensitization

• Sleep increasingly negatively affected by stress as insomnia continues (increased sleep reactivity)

• Increased risk for future insomnia• Increased vulnerability for depression and

anxiety

Pillai V 2016

Factors Contributing to Insomnia

• Medical & Psychiatric Disorders • Substances• Other Sleep Disorders

circadian, RLS, PLMS, OSA• Psychological Factors

stress• Poor Sleep Environment

room temperature, light, noise, bed partner• Poor Sleep Habits

activities in bed, naps, irregular schedule, timein bed

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Food & Sleep

• Randomized crossover, N=26 5 nights PSG, prepared meal vs ad libitum

• Results: Low fiber, saturated fat & sugar = lighter, less restorative & �fragmented sleep

SOL 17 vs 29 min p=0.0085�SWS p=0.04 ,

sugar assoc w/ �arousals p=0.03

St-Onge 2016

Medications that Can Disrupt Sleep

• Pain Medications containing caffeine: Fioricet, Fiorinal, Excedrine

• SSRIs: fluoxetine, citalopram• Tricyclic Antidepressants: amitriptyline,

clomipramine• ACE Inhibitors: benazepril, lisinopril

• Corticosteroids: prednisone• Statins: simvastatin, atorvastatin

Lenz 2014

Optimizing Treatment

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Reducing risk of disease in older adults with insomnia

Percentage of Subjects in High Risk Group

Carroll J 2015

High Risk>/= 4High-density lipoproteinLow-density lipoproteinTriglyceridesHemoglobinA1cGlucoseInsulinC-reactive proteinFibrinogen

P = 0.01

Incentives to Treat

AetnaFor every 20 nights employees get 7 hours or more of sleep they earn $25, up to $300

a year

Most Common Treatment Practices

No professional help (most)Reading, relaxation, nothing

“Natural”, herbal or OTC

Professional help (M.D.)Medication, often not an approved hypnotic

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Referring Practices for CBTI

Conroy 2015

PsychophysiologicalCognitive Arousal

Circadian Rhythms

Homeostatic SleepDrive

Cortico-Limbic CognitiveAffective Systems

Hypothalamic Sleep-Wake Centers

Brainstem ArousalCenters

Physiological Processes Neural Circuits

Treatment Effects On Sleep-Wake Function In Insomnia

Buysse 2011

CognitiveBehavioralTreatments

PharmacolgicTreatments

InsomniaSymptom Change

NHANES 1999 - 2010

• N = 32,328 community dwelling adults• 19.2% took at least one medication to

sleep• 55% of hypnotic users take other sedative

medication (opioids, Bz)• 10% take >3 other sedating medications

• 58% self medicate with an OTC

Bertisch 2014

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Ideal Medication

• No respiratory effects• No next day residual effects• No cognitive impairment• No rebound insomnia• No dependence or tolerance• Works entire night• No increased risk of falls• Action only affects sleep• Overdose safety

Actual Medications Used for Insomnia

• BZRAs most studied; S-T efficacy• Lack of adequate testing for many

regarding safety & efficacy; L-T efficacy not known

• Assoc with cognitive & behavioral changes, falls, fractures, dementia, auto accidents

• Increased safety issues in elderly –highest use

• Clinical trials focus on PIBertisch 2014Wilt 2016

Wenger 2013

Pharmacokinetic Profiles & Therapeutic Activity

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Complexities of Melatonin

• Hormone of darkness• Signals brain for sleep• Produced somewhat thru sleep until light to

aid in sleep maintenance• Dosage as sleep aid ?• Too much = groggy, headachy (hangover)• May misalign circadian rhythm – take too

late can delay, making it harder to initiate sleep

• Can cause decrease in normal production• Lack of regulation

Typical CBT-I Protocol

• Sleep hygiene & education

• Cognitive therapy

• Stimulus control

• Sleep restriction

• Relaxation (optional)

Comorbid Insomnia & CBTI

• Meta-analysis of 37 RCT studies, N=2189• CBTI more than twice as effective as

comparison conditions• Moderate to large effect sizes for SOL, WASO,

SE, & sleep quality (Drug studies had small to moderate)

• Response not affected by type of comorbidity• Improvement in comorbid conditions, more in

psychiatric than medical

Wu 2015Ong 2016Winkle 2014

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Comorbid Insomnia & CBTI: Insomnia Remission

Wu 2015

CBT-I: Efficacy of Delivery Modality

Insomnia SeverityLancee 2016N = 90 P<0.001

Brief Behavioral Treatment for Insomnia

• N = 118, Mean age = 64• 4 weekly 60 min group sessionsSleep Restriction, Cognitive Therapy, Education

Lovato 2014P = 0.05

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Comparing Treatments

CBT-I• Few adverse effects• Sustained benefits

after treatment• Requires time &

motivation• Compliance may be

problem

Medication• Potential risk of side

effects• Rapid relief• Limited evidence of

L-T efficacy

Combining Treatments

• How & when to combine CBTI & meds• Optimizing protocols for comorbidities

• Mimimizing SEs• Identifying responders & non-responders

Study in Progress

Edinger 2016Morin 2016

N = 140

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Results

• Remission <8 on ISI• BT & Zolp improve, but BT superior

• BT – ½ responded, 1/3 remitted• BT to CT improves more

• Zolp to BT better than Zolp to Traz

Edinger 2016Morin 2016

Stimulation Therapies

• Transcranial magnetic• Transcranial direct current

• Vestibular• Accoustic

American College of PhysiciansRecommendation

“All adult patients receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder.”

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Pearls

• Insomnia may have serious psychiatric, medical & QOL consequences, particularly with short sleep.

• Screen all patients for insomnia.

• Insomnia is not just a Sx of another disorder.

Pearls (2)

• CBT-IVery effective 1st line treatment for both primary & comorbid insomniaLow risk

• MedicationPotential serious adverse side effectsCan offer short term benefitsUse judiciously

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