Transcript This Slide Is to Be Used Only for Titles

Anxiety Disorders:
A Focus on Sleep
and Improving
Patient Outcomes
Thursday, March 6, 2008
Savannah, Georgia
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Introductions and
Program Objectives
Mark H. Pollack, MD
Director, Center for Anxiety and
Traumatic Stress Disorders
Massachusetts General Hospital
Professor of Psychiatry
Harvard Medical School
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Program Faculty
 Mark H. Pollack, MD
Center for Anxiety and
Traumatic Stress Disorders
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
 Michael W. Otto, PhD
Center for Anxiety and Related
Disorders
Boston University
Boston, Massachusetts
 Naomi M. Simon, MD, MSc
Center for Anxiety and
Traumatic Stress Disorders
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
 W. Vaughn McCall, MD, MS
Wake Forest University School
of Medicine
Winston-Salem, North Carolina
 Daniel S. Lewin, PhD, D.ABSM
Children’s National Medical Center
George Washington University
School of Medicine
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Program Agenda
9:00–9:15 am
9:15–10:15 am
Introductions and Program Objectives
Sleep-Wake Cycle Disturbances
and Anxiety
Mark H. Pollack, MD
Mark H. Pollack, MD
10:15–11:15 am
Psychosocial Interventions for
Insomnia: Methods, Outcomes, and
Applications to Patients with Anxiety
and Mood Disorders
An Overview of Sleep Disorders &
Pharmacotherapy
Lunch served
Michael W. Otto, PhD
Evaluating and Treating Comorbid
Sleep and Psychiatric Disorders in
Children
Evaluation and Management of
Insomnia in Home-Dwelling
Older Persons
Anxiety and Insomnia in Women
Discussion and Q&A
Daniel S. Lewin, PhD,
D.ABSM
11:15 am– 12:15 pm
12:15–1:15 pm
1:15–2:00 pm
2:00–2:45 pm
2:45–3:45 pm
3:45–4:00 pm
Mark H. Pollack, MD
W. Vaughn McCall, MD, MS
Naomi M. Simon, MD, MSc
Faculty
Learning Objectives
 After participating in this educational activity, the
participant should be better able to:
– Discuss and relate both naturally occurring sleep
compared to the effect of sleep disorders in the various
patient populations
– Improve the ability to differentially diagnose patients with
anxiety disorders and to understand the interplay with
sleep, particularly insomnia
– Engage patients and develop a management plan for
those with sleep and anxiety disorders
– Identify which patients to refer to other providers based on
differential diagnosis
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosures
 Dr. Mark H. Pollack has received grants or research support
from AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics,
Forest, GlaxoSmithKline, Janssen, Lilly, NARSAD, NIDA, NIMH,
Pfizer, Roche, Sepracor, UCB, and Wyeth. He has been a
consultant for AstraZeneca, Brain Cells, Bristol-Myers Squibb,
Cephalon, Dov, Forest, GlaxoSmithKline, Janssen, Jazz, Lilly,
Medavante, Neurocrine, Neurogen, Novartis, Otsuka, Pfizer,
Predix, Roche, sanofi-aventis, Sepracor, Solvay, Tikvah,
Transcept, UCB, and Wyeth. He has been a speakers bureau
member for Bristol-Myers Squibb, Forest, GlaxoSmithKline,
Janssen, Lilly, Pfizer, Solvay, and Wyeth, and has equity in
Medavante and Mensante.
 Dr. Michael W. Otto has been a consultant for Jazz and
Organon.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosures
 Dr. Daniel S. Lewin has no financial relationships over the past
12 months with any commercial organizations having a direct or
indirect interest in the subject matter of his presentation.
 Dr. Naomi M. Simon has received grants or research support
from AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest,
GlaxoSmithKline, Janssen, Lilly, NARSAD, NIMH, Pfizer,
Sepracor, and UCB. She has received honoraria for speaking
from Forest, Janssen, Lilly, Pfizer, Sepracor, and UCB, and has
been a consultant for Paramount Biosciences and Solvay.
 Dr. W. Vaughn McCall has received grants or research support
from GlaxoSmithKline, sanofi-aventis, and Sepracor. He has
been a consultant for Sepracor and a speakers bureau member
for GlaxoSmithKline and Sepracor.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Unlabeled Uses
 Please note that these presentations may
discuss unapproved or unlabeled uses of
drugs or devices. Any product mentioned in
the presentations should be used in
accordance with the prescribing information
provided by the manufacturer.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
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A green light indicates your answer was received
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There is no need to press “GO” or “?”
Please leave the ResponseCard on the
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Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep-Wake Cycle
Disturbances
and Anxiety
Mark H. Pollack, MD
Director, Center for Anxiety and
Traumatic Stress Disorders
Massachusetts General Hospital
Professor of Psychiatry
Harvard Medical School
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosure
 Dr. Mark H. Pollack has received grants or research support
from AstraZeneca, Bristol-Myers Squibb, Cephalon,
Cyberonics, Forest, GlaxoSmithKline, Janssen, Lilly,
NARSAD, NIDA, NIMH, Pfizer, Roche, Sepracor, UCB, and
Wyeth. He has been a consultant for AstraZeneca, Brain
Cells, Bristol-Myers Squibb, Cephalon, Dov, Forest,
GlaxoSmithKline, Janssen, Jazz, Lilly, Medavante,
Neurocrine, Neurogen, Novartis, Otsuka, Pfizer, Predix,
Roche, sanofi-aventis, Sepracor, Solvay, Tikvah, Transcept,
UCB, and Wyeth. He has been a speakers bureau member
for Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen,
Lilly, Pfizer, Solvay, and Wyeth, and has equity in Medavante
and Mensante.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Objectives
 Review prevalence and public health
impact of insomnia
 Describe relationship between anxiety
disorders and insomnia
 Discuss issues related to treatment of
sleep and anxiety
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
What Is “Insomnia”?
 Insomnia is a subjective complaint (symptom)
of one or more of the following:
– Inadequate sleep quality
– Insufficient amount of sleep
– Dissatisfaction with sleep timing
– Not feeling rested after habitual sleep episode
Kupfer DJ, Reynolds CF. N Engl J Med. 1997;336:341-346.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia Prevalence and Impact
 Prevalence of chronic insomnia in adults is 10%-15%1,2
– With varying degrees of severity
– Another 20%-30% have transient or occasional
sleep problems
 Chronic insomnia is associated with3-5:
–
–
–
–
Absenteeism
Accidents
Memory impairment
Greater health care utilization
1. Léger D, et al. J Sleep Res. 2000;9:35-42.
2. Ohayon MM, Roth MT. J Psychiatr Res. 2003;37:9-15.
3. Simon G, VonKorff M. Am J Psychiatry. 1997;154:1417-1423.
4. Benca RM. Psychiatr Serv. 2005;56:332-343.
5. Kim K, et al. Sleep. 2000;23:41-47.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Consequences of Chronic
Insomnia
Societal and Clinical Impact of Insomnia
 Societal
–
–
–
–
–
High direct and indirect costs
Increased utilization of inpatient and outpatient healthcare resources
Increased use of sleep-promoting medication
Reduced quality of life
Reduced daily functioning
 Personal
–
–
–
–
Increased daytime sleepiness with consequent psychomotor impairment
Increased risk of depression or anxiety
Increased risk of alcohol/drug abuse or dependence
Poorer outcomes in medical and psychiatric illnesses
Thase ME. Gen Hosp Psychiatry. 2005; 27:100-112.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep and Psychiatric Illness:
Bidirectional Relationship?
 Insomnia adversely affects quality of life in anxiety disorders
 Treatment of chronic insomnia may prevent the development
and persistence of mood and anxiety disorders
Anxiety/Mood
Disorders
?
Mellinger GD, et al. Arch Gen Psychiatry. 1985;42:225-232.
Lustberg L, Reynolds CF. Sleep Med Rev. 2000;4:253-262.
Stein MB, Barrett-Connor E. Am J Geriatr Psychiatry. 2002;10:568-574.
(after Stein, 2005)
Insomnia
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prevalence of Psychiatric
Disorders in Insomnia Sufferers
Drug Abuse
4.2
Other Psychiatric Disorder
5.1
Alcohol Abuse
7.0
Dysthymia
8.6
Major Depression
14.0
Anxiety Disorders
23.9
No Psychiatric Disorder
59.5
0
10
20
30
40
50
60
% of Respondents
Ford DE, Kamerow DB. JAMA. 1989;262:1479-1484.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia Is a Risk Factor for
Psychiatric Disorders
Incidence (%) Over 3.5 years
18
Incidence (%)
16
*
*
14
Insomnia, n=240
No Insomnia, n=739
12
10
8
6
*
4
2
0
Depression
Anxiety
Alcohol Abuse
Drug Abuse
*95% CI for odds ratio excludes 1.0.
Breslau N, et al. Biol Psychiatry. 1996;39:411-418.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and Mental Disorder
Trajectory
Insomnia
Depressive Disorder
Insomnia-Depressive Disorder
Anxiety Disorder
22%
Insomnia 34%
Insomnia-Anxiety Disorder
Ohayon MM, Roth MT. J Psychiatr Res. 2003;37:9-15.
40%
38%
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Causes of Chronic Insomnia In
Psychiatric Illness
 Is the underlying psychiatric disorder
adequately treated?
– A comorbid psychiatric disorder?
 Substance use/abuse?
 Medical illness?
 Medication side-effect?
 Primary sleep disorders?
Thase ME. Gen Hosp Psychiatry. 2005; 27:100-112.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
GAD and Sleep Disturbance
 Sleep disturbance is one of the criteria for the


diagnosis of GAD
Fatigue and irritability (two other criteria),
may be consequences of sleep loss
Excessive and uncontrollable worry (the core
cognitive symptom of GAD) at bedtime may
generate and maintain insomnia by
interfering with ability to fall asleep
Mellman TA. Psychiatr Clin N Am. 2006;29:1047-1058.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Characteristics of Sleep Disturbance
in Generalized Anxiety Disorder
% with Sleep Disturbance
90
80
77.3
70
63.6
56.8
60
47.4
50
40
30
20
10
0
At least one type
Initial insomnia
Sleep
Maintenance
Early morning
awakening
Note: Insomnia severity was not associated with GAD severity.
Total N=44.
Belanger L, et al. J Anxiety Disord. 2004;18:561-571.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
GAD and Sleep Parameters
 By PSG patients with GAD have:
– Increased sleep latency
– Increased wake time after sleep onset
– Reduced total sleep time and lower sleep
efficiency1
Monti JM, Monti D. Sleep Med Rev. 2000;4:263-276.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
GAD and Sleep Parameters
 Sleep in “pure” GAD differentiated from major
depression
– Reduction in REM latency seen in endogenous
major depression is generally not seen in nondepressed patients with GAD1-3
 However, differences in sleep of uncertain
clinical diagnostic utility given high rates of
depressive comorbidity in practice
1. Saletu-Zyhlarz G, et al. Neuropsychobiology. 1997;36:117-29.
2. Arriaga F, Paiva T. Neuropsychobiology. 1990-1991;24(3):109-14.
3. Papadimitriou GN, et al. J Affect Disord. 1988;15:113-8.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disordered Sleep in PTSD
 Difficulty falling asleep — greater onset latency
 Difficulty with sleep maintenance
– REM-related awakenings and nightmares
 Changes in REM
– More total REM or higher REM density
– Fragmented (more frequent short duration)
– Reduced heart-rate variability (NE-related)
 Sleep disturbances at one-month post-trauma may
predict PTSD evolution and ultimate chronicity
Mellman TA, et al. Am J Psychiatry. 1995;152:110-115.
Mellman TA, et al. Sleep. 1997;20:46-51.
Mellman TA, et al. Am J Psychiatry. 2002;159:1696-1701.
DeViva JC, et al. Behav Sleep Med. 2004;2:162-176.
Hurwitz TD, et al. Biol Psychiatry. 1998;44:1066-1073.
Ross RJ, et al. Sleep. 1994;17:723-732.
Ross RJ, et al. Biol Psychiatry. 1999;45:938-941.
Koren D, et al. Am J Psychiatry. 2002;159:855-857.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
How Might the Pathophysiology of
Anxiety Disorders Impair Sleep?
 “Hyperarousal” theory
– Increased arousal (amygdala? brain stem?)
– Increased cortical activity due to ruminations
 Comorbid conditions and drugs
– Affective disorders
– Substance abuse
– Prescribed Rx (e.g., antidepressants)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
How Might Disturbed Sleep Influence
Pathogenesis and Treatment of Anxiety Disorders?
 Disturbed sleep the night before an event
– Effects on emotional learning
• Shifts bias towards negative
emotional learning
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Encoding Results: Behavioral
1.2
*
1.0
0.8
0.6
0.4
0.2
0.0
Memory Retention (d-prime)
Memory Retention (d-prime)
Sleep Deprivation
1.6
Sleep Control
**
n.s.
1.4
1.2
n.s.
1.0
0.8
0.6
0.4
0.2
0.0
Positive
ALL MEMORY TYPES
Negative
Neutral
MEMORY TYPES SEPARATED
*p≤0.05, **p≤0.01
Walker MP, Stickgold, R. Annu Rev Psychol. 2006;57:139:166.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Animal Studies of Sleep Deprivation Effects
on Fear Conditioning and Extinction
 Sleep (REM and NREM) deprivation before
conditioning in rats (Ruskin et al, 2004)
– No change in amygdala-based fear conditioning
– Deficits in hippocampal-based contextual memory
 REM deprivation in rats after conditioning
(Silvestri, 2005)
– Normal retention of conditioned fear
– Impaired extinction consolidation
Ruskin DN, et al. Eur J Neurosci. 2004;19:3121-3124.
Silvestri AJ. Physiol Behav. 2005;84:343-349.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Disturbance and Anxiety:
Moderating Factors
 Poor sleep shifts the bias toward negative
emotional learning and may disrupt extinction
consolidation and recall
Thus, poor sleep quality may:
– Contribute to the pathogenesis of anxiety
disorders and/or:
– Undermine the effectiveness of treatment
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment Goals for Anxiety
and Insomnia
 Improve anxiety and the associated symptomatology
 Improve sleep
– Reduce time it takes to fall asleep
– Increase sleep time to levels that support daytime
functioning
– Reduce awakenings during the night
– Eliminate nightmares and/or unwanted sleep behavior
– Enhance subjective sleep quality
– Restore confidence in the patient’s ability to sleep and to
handle sleeplessness
Mellman TA. Psychiatr Clin N Am. 2006;29:1047-1058.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
General Principles in the
Management of Insomnia
 Treat underlying cause(s)
 Promote good sleep habits
 Initiate behavioral intervention
 Prescribe sedatives, hypnotics: use in
combination with behavioral management
Kupfer DJ, Reynolds CF. N Engl J Med. 1997;336:341-346.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
CBT Approaches to Insomnia May Be
Helpful in Setting Anxiety Disorders
Technique
Aim
Sleep Hygiene
Promote habits that help sleep; provide
rationale for subsequent instructions
Stimulus Control Therapy
Strengthen bed and bedroom as sleep stimulus
Sleep Restriction
Restrict time in bed to improve sleep depth &
consolidation
Relaxation
Reduce arousal and decrease anxiety
Paradoxical Intention
Mitigate performance anxiety that impedes
sleep onset
Cognitive-Behavioral
Therapy (CBT)
Combines sleep reduction, stimulus control
techniques, and sleep restriction with cognitive
therapy, addressing thoughts and beliefs that
interfere with sleep
Morin, CM. J Clin Psychiatry. 2004;65(suppl 16):33-40.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment of Anxiety and
Insomnia
 Pharmacologic and cognitive-behavioral
therapy of anxiety improves associated
sleep disturbance
Belanger L, et al. J Anxiety Disord. 2004;18:561-571.
Morin CM, et al. JAMA. 1999;281:991-999.
Rosenthal M. J Clin Psychiatry. 2003;64:1245-1249.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Mean (SEM) PSQI Global Score
Reduction in Sleep Disturbance During
Treatment for GAD with Paroxetine and Tiagabine
14
12
*
10
*
8
*
*
6
4
2
0
Baseline
Wk 4
Wk 10
Tiagabine (n=20)
*p<0.05 relative to baseline.
No significant difference between treatments.
Rosenthal M. J Clin Psychiatry. 2003;64:1245-1249.
Baseline
Wk 4
Wk 10
Paroxetine (n=20)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Impact of Worry-Focused CBT for GAD
vs. Waitlist on Concomitant Insomnia
Insomnia Severity Index Score
14
Baseline
Endpoint
12
10
8
6
4
2
0
CBT for GAD
p<0.01; N=44.
Belanger L, et al. J Anxiety Disord. 2004;18:561-571.
Waitlist Control
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment of Anxiety and
Insomnia
 Does targeted treatment of insomnia
improves anxiety?
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Targeted Insomnia Treatment in GAD:
Escitalopram (ESC) plus Eszopiclone or
Placebo – Effect on Sleep Latency
Minutes (median)
70
Placebo + ESC
60
Eszopiclone + ESC
50
40
30
*
*
1
2
*
*
*
20
10
0
0
3
4
5
6
Double-Blind Treatment Period
7
8
9
10
SB Run-Out
*p<0.0005 vs. placebo
Pollack MH, et al. Arch Gen Psych (in press).
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Targeted Insomnia Treatment in GAD:
Escitalopram (ESC) plus Eszopiclone or
Placebo – Effect on Anxiety (HAM-A)
Placebo + ESC
30
Eszopiclone + ESC
Mean Score
25
*
*
20
*
*
*
*
15
10
5
0
BL
1
2
4
6
8
10
Week
*p<0.05 vs. placebo; Week 10 = end of single-blind placebo run-out period.
Pollack MH, et al. Arch Gen Psych (in press).
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Targeted Insomnia Treatment in GAD: Escitalopram
(ESC) Plus Eszopiclone or Placebo – Effect on Anxiety
(HAM-A excluding insomnia item)
Placebo + ESC
30
Eszopiclone + ESC
Mean Score
25
20
*
*
*
*
15
10
5
0
BL
1
2
4
6
8
10
Week
*p<0.05 vs. placebo; Week 10 = end of single-blind placebo run-out period.
Pollack MH, et al. Arch Gen Psych (in press).
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Therapeutic Approach to
Nocturnal Panic (NP) Attacks
 May occur as part of panic disorder
(44%-71% at least once) or PTSD
– Non-REM event in Stage II-III transition
– Not clear difference in sleep architecture or
insomnia severity
 Some support for CBT specific to NP
 Lack data on pharmacotherapy approaches
 May improve with treatment of primary
disorder
Craske MG, Tsao JC. Sleep Med Rev. 2005;9:173-184.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Limited Pharmacotherapy Data for
PTSD-Related Sleep Disturbance
 SSRIs may have negative effects on sleep physiology
with  REM and  arousals
– But data support improved subjective sleep quality
 Negative single-blind crossover of clonazepam
2 mg HS vs. placebo in combat PTSD
– No effect on nightmares
– Only one person continued clonazepam after trial
 Open support for trazodone (survey n=74)
– Helpful for nightmares, sleep initiation, and maintenance
in veterans with chronic PTSD
– Dosed 50-150 mg HS
– 12% reported priapism
Cates ME, et al. Ann Pharmacother. 2004:38:1395-1399.
Singareddy RK, Balon R. Ann Clin Psychiatry. 2002:14:183-190.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Hypnotic Medication in
Aftermath of Trauma
 Admitted to medical trauma center and



manifesting early PTSD symptoms (N=22)
Recalled incident and at least moderate
impairment of sleep initiation or maintenance
Treated 14.3  10 days post-trauma
Randomized to receive temazepam x 7 days
(i.e., 30 mg x 5 nights and 15 mg x 2 nights)
vs. placebo
Mellman TA, et al. J Clin Psychiatry. 2002;63:1183-1184.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Potential Impact of Early
Benzodiazepine on Recovery in PTSD
% with PTSD at
6-Week Follow-Up
80
70
60
55
50
40
27
30
20
10
0
Temazepam
Control
Acute improvement in sleep in temazepam group but no difference upon discontinuation.
Mellman TA, et al. J Clin Psychiatry. 2002;63:1183-1184.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Alpha1 Adrenergic Antagonist for Nightmares
and Insomnia in Chronic Combat PTSD:
Prazosin vs. Placebo
4
Prazosin (mean 9.5 mg HS)
Change in Score
3.5
Placebo
3
2.5
2
1.5
1
0.5
0
CAPS Nightmares
CAPS Insomnia
p<0.01; N=10. CAPS: Clinician-Administered PTSD Scale.
Raskind MA, et al. Am J Psychiatry. 2003;160:371-373.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Improved Sleep in Open-Label
Quetiapine for PTSD (N=20)
8
**
7
6
5
4
3
**
PSQI Change Score
9
2
**
1
**
0
Global score
Quality
Latency
Duration
**p<0.01; PSQI = Pittsburgh Sleep Quality Index.
Robert S, et al. J Clin Psychopharmacol. 2005;25:387-388.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Summary
 Sleep disturbance may resolve with treatment of
primary anxiety disorder, but not always
 Treatment approaches for primary insomnia are
likely useful in setting anxiety
– May provide more rapid relief and improve overall
outcomes
 All patients should be educated about sleep
hygiene rules
 Both CBT and pharmacologic approaches to
insomnia appear to be effective
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Psychosocial Interventions
for Insomnia: Methods,
Outcomes, and Applications
to Patients with Anxiety
and Mood Disorders
Michael W. Otto, PhD
Director, Center for Anxiety and Related Disorders
Professor of Psychology
Boston University
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosure
 Dr. Michael W. Otto has been a consultant
for Jazz Pharmaceuticals and Organon.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Overview of
Interventions
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
History of Interventions
 Relaxation



– Schultz and Luthe (1959)
– Jacobson (1964)
– Borkovec & Fowler (1973)
– Nicassion & Bootzin (1974)
Conditioning Model & Stimulus Control
– 1970s Bootzin
Attention to Cognitive Arousal and Cognitive Distortions
– Psychoeducation and cognitive restructuring (Edinger)
Second Generation Treatments
– Comprehensive CBT (Edinger, Morin, Espie)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Stimulus Control
 Conditioning Model
 Re-associate bed and bedtime with sleep
rather than
– Anxiety
– Frustration
– Effort
 In bed when sleepy and only for sleep
 Use sleep restriction to drive a positive
(sleep-filled) association with bed
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Stimulus Control Approach to
Treatment of Insomnia
 Go to bed only when sleepy
 Use the bed or bedroom only for sleeping
– Do not read, watch TV, or eat in bed
 Go to bed when sleepy
 Get out of bed when unable to sleep
 Arise at the same time every morning
 Do not nap during the day
Morin CM. J Clin Psychiatry. 2004;65(suppl 16):33-40.
Bootzin RR, et al. In: Hauri PJ, ed. Case Studies in Insomnia. 1991:19-28.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Restriction
 Select time in bed to represent the average



total sleep time (plus 30 minutes)
Work with the patient on sleep onset and
offset time
Joyfully explain rationale and likelihood of
less time in bed (and potential for fatigue)
Adjust time in bed according to the target of
85% sleep efficiency
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Interventions
 Also oriented to re-associating meanings



associated with bed, bedtime, and sleep
Eliminate anxiogenic, arousal-inducing, and
catastrophic thoughts
Targeting both daytime functioning and
sleep performance
Includes informational interventions (sleep
hygiene)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Principles of Sleep Hygiene








1NHLBI
Reduce time in bed; regular sleep/wake cycle1-3
Regular exercise in the morning and/or afternoon1,3
Avoid exposure to bright light at night1,3
Avoid heavy meals or drinking within 3 hours of bed1
Enhance sleep environment1,3
Avoid caffeine, alcohol, and nicotine1,3
Practice relaxing bedtime routine1-3
Avoid “watching the clock”
Working Group on Insomnia. 1998. NIH Publication 98-4088.
2Kupfer DJ, Reynolds CF. N Engl J Med. 1997;336:341-346.
3Lippmann S, et al. South Med J. 2001;94:866-873.
CBT for Insomnia
Technique
Sleep Hygiene
Aim
Stimulus Control
Therapy
Strengthen bed and bedroom as sleep
stimulus
Sleep Restriction
Restrict time in bed to improve sleep depth
& consolidation
Relaxation
Reduce arousal and decrease anxiety
Paradoxical Intention
Mitigate performance anxiety that impedes
sleep onset
Cognitive-Behavioral
Therapy (CBT)
Combines sleep reduction, stimulus control
techniques, and sleep restriction with
cognitive therapy, addressing thoughts and
beliefs that interfere with sleep
Promote habits that help sleep; provide
rationale for subsequent instructions
Morin CM. J Clin Psychiatry. 2004;65(suppl 16):33-40.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Overview
of the Evidence
for Efficacy
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Big Picture on Meta-analyses
 CBT for Insomnia produces meaningful

improvements in 70% to 80% of patients with
insomnia
Treatment gains are maintained over time
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Meta-analysis of Nonpharmacologic
Interventions for Insomnia
 59 treatment outcome studies (2,102) patients
 Interventions (mean of 5 hours of therapy)
 Effect sizes
– d = 0.88 for sleep latency
– d = 0.65 for time awake after sleep onset
 Better off than 81% and 74% of untreated control
subjects
 Stimulus Control and Sleep Restriction
 Great maintenance of treatment gains
Morin CM, et al. Am J Psychiatry. 1994;151:1172–1180.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Efficacy of Nonpharmacologic
Interventions for Insomnia
Meta-Analysis of 59 Trials (N = 2,102)
Pretreatment
70
Posttreatment
Sleep-Onset Latency
P<0.001*
60
Minutes
Minutes
50
40
30
20
10
0
Control
Nonpharmacologic
Conditions
Treatments
Time Awake After Sleep Onset
P<0.001*
80
70
60
50
40
30
20
10
0
Control
Nonpharmacologic
Conditions
Treatments
*Control group posttreatment vs. nopharmacologic group posttreatment.
Morin CM, et al. Am J Psychiatry. 1994;151:1172–1180.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Meta-analysis of Behavioral
Treatments for Insomnia
 23 randomized trials
 Moderate to large effect sizes
 CBT = BT = Relaxation
 Middle aged and older adults achieve similar
outcomes
Irwin MR, et al. Health Psychol. 2006;25:3-14.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparative Meta-analysis of Behavioral
Treatments vs. Pharmacotherapy for Insomnia
 21 randomized trials (470 subjects), use of


pre- to post-treatment d scores
Limited to CBT studies utilizing stimulus
control and/or sleep restriction
Medications: flurazepam, lorazepam,
temazepam, triazolam, quazepam, zolpidem
Irwin MR, et al. Health Psychol. 2006;25:3-14.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparative Meta-analysis of Behavioral
Treatments vs. Pharmacotherapy for Insomnia
 Generally no difference in outcomes, but
Irwin MR, et al. Health Psychol. 2006;25:3-14.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparative Meta-analysis of Behavioral
Treatments vs. Pharmacotherapy for Insomnia
 Generally no difference in outcomes, but
 CBT showed advantage for greater
reductions in sleep latency than medications
(43% vs. 30%)
Irwin MR, et al. Health Psychol. 2006;25:3-14.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparative Meta-analysis of Behavioral
Treatments vs. Pharmacotherapy for Insomnia
 Generally no difference in outcomes, but
 CBT showed advantage for greater


reductions in sleep latency than medications
(43% vs. 30%)
Total sleep time improvements modest in
both treatments: 12% pharmacotherapy, 6%
CBT
Sleep quality: 20% pharmacotherapy, 28%
CBT
Irwin MR, et al. Health Psychol. 2006;25:3-14.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparison Trial of
CBT and Pharmacotherapy
 No differences in total sleep time
90
 More normal sleepers with CBT alone
80
Sleep Efficiency
70
60
Pre
Mid
Post
1-mo FU
50
40
30
Post = 2-wk
no treatment
period.
20
10
0
Combined
CBT
CBT = 4 individual and 1 phone session over 8 weeks.
Med = zolpidem, nightly for 1 mo, taper over 12 days.
Jacobs GD, et al. Arch Intern Med. 2004;164:1888-1896.
Med
Placebo
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparison Trial of CBT and
Pharmacotherapy (Late-Life Insomnia)
100
90
Sleep Efficiency
80
70
Pre
Post
3-mo FU
12-mo FU
24-mo FU
60
50
40
30
20
10
0
Combined
CBT
Med
Placebo
CBT = 8 weekly group sessions.
Med = temazepam x 8 weeks.
Morin CM, et al. JAMA. 1999;281:991-999.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
CBT, Temazepam, or the Combination for
Chronic, Primary Late-Life Insomnia
Morin CM, et al. JAMA. 1999;281:991-999.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
CBT for BZ Tapering for Sleep
 Discontinuing benzodiazepines (BZs) after
chronic use
– 76 older adults (mean age 62.5 years) with
chronic insomnia and mean 19.3 years of BZ
medications (67 mg diazepam equiv.)
– 3 conditions
• Slow taper (over 10 weeks), 25% every 2 weeks
• Group CBT
• Group CBT plus slow taper
Morin CM, et al. Am J Psychiatry. 2004;161:332-342.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
CBT for BZ Tapering for Sleep
 Greater likelihood of drug-free participants

with CBT+ slow taper
Everyone gets better in terms of sleep over
time, only significant difference was in total
sleep time (more benefits for CBT)
Morin CM, et al. Am J Psychiatry. 2004;161:332-342.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
CBT for BZ Tapering for Sleep
90
80
ITT % Drug-Free
70
Post
3-mo
12-mo
60
50
40
30
20
10
0
Med Taper
CBT
CBT+MT
ITT = intent-to-treat
Morin CM, et al. Am J Psychiatry. 2004;161:332-342.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
CBT for BZ Tapering for Sleep
160
Total Wake Time
140
120
100
Pre
Post
3-mo
12-mo
80
60
40
20
0
Med Taper
Morin CM, et al. Am J Psychiatry. 2004;161:332-342.
CBT
CBT+MT
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
A Range of Modalities
of Treatment Work
 Comparison of:
– Individual therapy
– Group therapy
– Telephone consultation
 All offered
– Stimulus control
– Sleep restriction
– Cognitive therapy
– Sleep hygiene
Bastien CH, et al. J Consult Clin Psychol. 2004;72:653-659.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
A Range of Modalities
of Treatment Work
 Results
– All three led to significant improvements that
were maintained at 6-month follow-up on selfreport
– Total wake time dropped to almost half
– 80% sleep efficiency ranged from 56% to 82%
at follow-up
Bastien CH, et al. J Consult Clin Psychol. 2004;72:653-659.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comparison of Three Methods
of Delivering CBT
180
Pre
Post
3-mo FU
6-mo FU
Wake Time in Minutes
160
140
120
100
80
60
40
20
0
Individual
Bastien CH, et al. J Consult Clin Psychol. 2004;72:653-659.
Group
Telephone
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment of Anxiety and
Insomnia
 Pharmacologic and cognitive-behavioral
therapy of anxiety improves associated
sleep disturbance
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
% Reporting Sleep Complaint
Insomnia and GAD
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Difficulties Initiating
Sleep
Belanger L, et al. J Anxiety Disord. 2004;18:561-571.
Difficulties
Maintaining Sleep
Wake Too Early
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Impact on Concomitant Insomnia of
Worry-Focused CBT for GAD vs. Waitlist
Insomnia Severity Index Score
14
Baseline
Endpoint
12
10
8
6
4
2
0
CBT for GAD
Waitlist Control
P<0.01, CBT endpoint vs. waitlist endpoint; N=44.
Belanger L, et al. J Anxiety Disord. 2004;18:561-571.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 188 patients randomized to CPT, Prolonged
Exposure, or Minimal Attention
– Twice weekly sessions over 6 weeks
– Analysis of patients who received CPT or PE
CPT = cognitive processing therapy
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 92% of the sample had sleep disturbance

(greater than 5 on PSQI)
PSQI scores linked to CAPS score at
baseline (r = 0.53)
PSQI = Pittsburgh Sleep Quality Index.
CAPS = Clinician-Administered PTSD Scale.
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 Significant improvement in PSQI scores with

CBT (M 10.6 to 7.4)
Improvements linked to CAPS changes
(r = 0.47)
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 AND…
 PSQI scores at post-treatment predict
3-month follow-up CAPS (over and
above posttreatment CAPS scores)
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 Consistent with depression studies
– Poorer treatment response (Buysee et al,
1997; Dew et al, 1996; Winokur & Reynolds,
1994)
– Risk for relapse (Reynolds et al, 1997; Brower
et al, 2001)
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 PSQI scores at post-treatment predict
3-month follow-up CAPS (over and
above posttreatment CAPS scores)
– Consistent with depression studies
• Poorer treatment response (Buysee et al,
1997; Dew et al, 1996; Winokur &
Reynolds, 1994)
• Risk for relapse (Reynolds et al, 1997;
Brower et al, 2001)
 But
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 But
 Failure to replicate in the next study
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia and CBT for PTSD
(Collaboration with Resick)
 Conclusions
– Given results to date – be confident that some
pre-treatment sleep disruption will resolve
with CBT
– Some will not
– Treating the residual sleep symptoms may
help ultimate outcome
Gutner CA, et al. In prep.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Assessment and
the Application
of CBT for Insomnia
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Books I Like
 Perlis, Jungquist, Smith, & Posner (2005).

Cognitive Behavioral Treatment of Insomnia.
New York: Springer.
Edinger & Carney (2008). Overcoming
Insomnia: A Cognitive-Behavioral Therapy
Approach Workbook (Treatments that Work).
New York: Oxford University Press USA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Keep Sleep Logs
 Time to bed
 Time to fall asleep
 Time awakening in the AM
 Time up in the AM
 Naps
 Rating of quality of sleep
 Rating of feeling rested
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Logs








Attend to erratic bed times
Attend to erratic rising times
Attend to ratings of sleep quality vs. sleep time
Changes to sleep latency with changed bed
times
Time awakening in the AM
Naps
Rating of quality of sleep
Rating of feeling rested
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Log – Edinger & Carney
Edinger JD, Carney CE. Overcoming Insomnia: A Cognitive-Behavioral
Therapy Approach Workbook. New York: Oxford UP USA, 2008.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Questionnaires
 Insomnia Severity Index (Morin, 1993)
– 7 item questionnaire that indicates perceived insomnia
severity
 Pittsburgh Sleep Quality Index (Buysee et al,
1989)
– Four open-ended questions and 19 self-rated items
• Score over 5 indicates sleep problems
 Epworth Sleepiness Scale (Johns, 1991)
Morin CM. Insomnia: Psychological Assessment and Management. New York: Guilford Press, 1993.
Buysse DJ, et al. Psychiatry Res. 1989;28:193-213.
Presented at the 28th Annual Conference
Johns MW. Sleep. 1991;14:540-545.
Anxiety Disorders Association of America
Stimulus Control Approach to
Treatment of Insomnia
 Go to bed only when sleepy
 Use the bed or bedroom only for sleeping
– Do not read, watch TV, or eat in bed
 Go to bed when sleepy
 Get out of bed when unable to sleep
 Arise at the same time every morning
 Do not nap during the day
Morin CM. J Clin Psychiatry. 2004;65(suppl 16):33-40.
Bootzin RR, et al. In: Hauri PJ, ed. Case Studies in Insomnia. 1991:19-28.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Restriction
 Select time in bed to represent the average



total sleep time (plus 30 minutes)
Work with the patient on sleep onset and
offset time
Joyfully explain rationale and likelihood of
less time in bed (and potential for fatigue)
Adjust time in bed according to the target of
85% sleep efficiency
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Titration for
Restriction Treatment
 Sleep efficiency >90% – add 20 min sleep
 Sleep efficiency 85%-90%
 Sleep efficiency <85% – reduce total sleep
opportunity
 Assess noncompliance
 Assess sleep hygiene
Perlis ML, et al. Cognitive Behavioral Treatment of Insomnia. New York: Springer, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Nonadherence
 Assess prescribed time to bed and time out
of bed
– vs. actual times
– vs. naps
Perlis ML, et al. Cognitive Behavioral Treatment of Insomnia. New York: Springer, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Nonadherence
 Wanted to but couldn’t
– “not tonight; I will start tomorrow night”
– “It is so warm and comfy in bed; the cold will
wake me right up if I get out of bed”
Perlis ML, et al. Cognitive Behavioral Treatment of Insomnia. New York: Springer, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Nonadherence
to Sleep Restriction
 Intervention
– “it is a bad thing to be awake when reason
sleeps”
– 30%-50% improvement short term
– Add the cost:
• 3 nights of insomnia per week for years
• 150 nights of insomnia per year
• vs. 14 to 21 really bad nights trying program
Perlis ML, et al. Cognitive Behavioral Treatment of Insomnia. New York: Springer, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Nonadherence
 Simply could not
– Fell asleep early
 Intervention
– Reschedule activities in evening
• Exercise
• Activities
• Cold compress
Perlis ML, et al. Cognitive Behavioral Treatment of Insomnia. New York: Springer, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Nonadherence
 Did not want to
 Intervention
– Review rationale and cost of current strategies
Perlis ML, et al. Cognitive Behavioral Treatment of Insomnia. New York: Springer, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Perceptions of Sleep Quality
 Impairments in daytime functioning are only

indirectly linked to objective amounts of sleep
False feedback about hours slept
–
–
–
–
Increased negative thoughts about sleep
Monitoring of sleep-related symptoms
Amount of daytime sleepiness
Changes in behavior linked to sleep concerns
(e.g., canceling appointments or reducing
exercise)
Semler CN, Harvey AG. Behav Res Ther 2005;43:843-856.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Biases
 Tendency to attend to negative vs. positive


stimuli (e.g., dot probe task)
Negative bias is linked to anxiety disorders
Greater negative bias is predictive of
greater anxiety in response to a stressful
event (e.g., an accident video)
MacLeod C, et al. J Abnorm Psychol. 2002;111:107-123.
Mackintosh B, et al. Behav Ther. 2006;37:209-222.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Biases – Insomnia
 Those with Primary Insomnia vs. good
sleepers vs. those with delayed sleep phase
disorder:
– Greater bias toward sleep related words
among Primary Insomniacs1
– Also an interpretative bias toward threatrelated interpretations of sleep stimuli2
1. MacMahon KM, et al. Sleep. 2006;29:1420-1427.
2. Ree MJ, et al. Sleep. 2006;29:1359-1362.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Value of Placebo for Sleep
 Placebo Condition
– 7.5 min sleep onset latency, 19.6 min
subjective
– 21.4 min WASO (Wake-time After Sleep Onset)
– 18.3 min Total Sleep Time (objective)
– 31.1 min Total Sleep Time (subjective)
 Differences
– Placebo beats waitlist for sleep onset latency
and Total Sleep Time
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Interventions
for Insomnia
 Decrease misattribution and amplification of



consequences insomnia
– e.g., “I can’t function at work without 8 hours of sleep.”
Correct unrealistic sleep expectations
– e.g., “I should never wake up at night.”
Decrease performance anxiety and learned helplessness
Correct faulty beliefs and dysfunctional sleep-related
practices
– Sleep hygiene rules and target maladaptive coping
– Educate about causes of insomnia
Morin CM. J Clin Psychiatry. 2004;65(suppl 16):33-40.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Restructuring in Session
(Belanger, Savard & Morin)
“Close your eyes and imagine the following: It is
3AM and you have been tossing and turning for
hours. You have an important meeting tomorrow,
but can’t seem to get to sleep. Tell me your
thoughts at this moment.”
Belanger L, et al. Behav Sleep Med. 2006;4:179-198.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Restructuring
 Examine the evidence for the thought
 Generate alternative explanations
 De-catastrophize
 Debunk “shoulds”
 Find the logical error
 Test out its helpfulness
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive Errors of Depression
 All-or-nothing thinking
 Overgeneralization
 Mental filter
 Disqualifying the positive
 Jumping to conclusions
 Personalization
Burns DD. Feeling Good: The New Mood Therapy. 1980.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Questions Used to Formulate
Rational Response
 What is the evidence that the automatic




thought is true? Not true?
Is there an alternative explanation?
What is the worst that could happen?
Would I live through it?
What’s the best that could happen?
What’s the most realistic outcome?
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Questions Used to Formulate
Rational Response (cont’d)
 What is the effect of my believing the


automatic thought?
What is the cognitive error?
If a friend were in this situation and had
this thought, what would I tell him/her?
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Event
Automatic Thought Record
Automatic
Thought
Feeling(s)
Response
Outcome
Rate belief
0%-100%
Rate intensity
0%-100%
What is the error?
What is a more
helpful way to
think about the
event?
Re-rate belief
in automatic
thought and
intensity of
feeling
Adapted from a worksheet in use by J. Beck and A.T. Beck.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Relaxation Training
 Tense Relax Method
 7 seconds tension, at least twice as long




relaxation
Feel the difference (repeat the difference)
Use of cued-relaxation
Use of imagery
“Enjoying being in bed”
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Worry Time
 Early evening
 Select place (desk)
 Paper and pencil
 40 min followed by relaxation
 Delay next worry till next worry time
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Session 1: Edinger & Carney
 Psychoeducation
– 2 goals
• Overcome misconceptions and anxiety-provoking beliefs about
sleep
• Develop rationale for interventions to follow
 How much sleep do you need?
–
–
–
–
Great variability (6-8 hours vs. 3-4 vs. 10-12)
Find sleep that allows alertness and energy during day
Get rid of old notions about needs
Circadian rhythms
 Cost of sleeping in and naps
– Don’t try to recover sleep
– Don’t worry about lost sleep
Edinger JD, Carney CE. Overcoming Insomnia: A Cognitive-Behavioral
Therapy Approach Workbook. New York: Oxford UP USA, 2008.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Session 1: Rules for Healthier
Sleeping (Edinger & Carney)







Select a standard wake-up time
Use the bed only for sleeping
Get up when you can’t sleep
Don’t worry or plan in bed
Avoid daytime napping
Go to bed when you are sleepy but not before the time
suggested
Time in Bed Prescription
– Time in BED = Average Totals Sleep Time + 30 minutes
– With success, adjust by 15 minutes (targeting >85% sleep
efficiency)
Edinger JD, Carney CE. Overcoming Insomnia: A Cognitive-Behavioral
Therapy Approach Workbook. New York: Oxford UP USA, 2008.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Session 1: Sleep Hygiene
(Edinger & Charney)
 Limit caffeine
 Limit alcohol
 Moderate exercise (late afternoon, early
evening)
 Manage hunger (night snack)
 Quiet and dark bedroom (white noise
machine – NewYorker)
 Not too warm in the bedroom (below 75°)
Edinger JD, Carney CE. Overcoming Insomnia: A Cognitive-Behavioral
Therapy Approach Workbook. New York: Oxford UP USA, 2008.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Session 2: Edinger & Charney
 Managing expectations
– With consistent adherence to the behavioral
strategies – expect marked changes in wake
time during the night within 2 to 3 weeks
– Expect some sleepiness as the program
starts
• Caution about dangerous activities
Edinger JD, Carney CE. Overcoming Insomnia: A Cognitive-Behavioral
Therapy Approach Workbook. New York: Oxford UP USA, 2008.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Session 2: Cognitive Restructuring
(Edinger & Charney)
 Structured worry time
– Write it out
– Proposed solutions
– Dispense with thinking through worries till the
next evening (well before bedtime)
Edinger JD, Carney CE. Overcoming Insomnia: A Cognitive-Behavioral
Therapy Approach Workbook. New York: Oxford UP USA, 2008.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
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Presented at the 28th Annual Conference
Anxiety Disorders Association of America
An Overview of
Sleep Disorders &
Pharmacotherapy
Mark H. Pollack, MD
Director, Center for Anxiety and Traumatic
Stress Disorders
Massachusetts General Hospital
Professor of Psychiatry
Harvard Medical School
After John Winkelman, MD, PhD
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosure
 Dr. Mark H. Pollack has received grants or research support
from AstraZeneca, Bristol-Myers Squibb, Cephalon,
Cyberonics, Forest, GlaxoSmithKline, Janssen, Lilly,
NARSAD, NIDA, NIMH, Pfizer, Roche, Sepracor, UCB, and
Wyeth. He has been a consultant for AstraZeneca, Brain
Cells, Bristol-Myers Squibb, Cephalon, Dov, Forest,
GlaxoSmithKline, Janssen, Jazz, Lilly, Medavante,
Neurocrine, Neurogen, Novartis, Otsuka, Pfizer, Predix,
Roche, sanofi-aventis, Sepracor, Solvay, Tikvah, Transcept,
UCB, and Wyeth. He has been a speakers bureau member
for Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen,
Lilly, Pfizer, Solvay, and Wyeth, and has equity in Medavante
and Mensante.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Disorders
 Insomnias
– Primary insomnia, psychiatric/medical disorders, RLS,
medications
 Hypersomnias
– Sleep apnea, medications, periodic leg movements of
sleep
 Parasomnias
– Sleepwalking, sleep terrors, REM sleep behavior
disorder
 Circadian rhythm disorders
– Shift work sleep disorder, delayed sleep phase disorder
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
DSM-IV Insomnia
Insomnia
Difficulty initiating or
maintaining sleep, or
nonrestorative sleep for
≥1 month
Primary
Insomnia
Comorbid
Insomnia
Without clear
precipitant;
“hyperarousal”
Associated with a
psychiatric, medical,
or sleep disorder
MUST cause distress or
impairment in social,
occupational, or other areas
of functioning
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prevalence of Chronic Insomnia
in the General Adult Population
% with Insomnia
20
17.7
16.8
15
11.7
10.2
10.0
9.0
10
5
0
Ford
1989
Ohayon
1998
Ohayon
2001
AncoliIsrael
1999
Ishigooka
1999
Simon
1997
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Consequences of
Insomnia
Why Should We Care?
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia Is a Risk Factor for
Psychiatric Disorders
Incidence (%) Over 3.5 years
18
Incidence (%)
16
*
*
14
Insomnia, n=240
No Insomnia, n=739
12
10
8
6
*
4
2
0
Depression
Anxiety
Alcohol Abuse
Drug Abuse
*95% CI for odds ratio excludes 1.0.
Breslau N, et al. Biol Psychiatry. 1996;39:411-418.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Transient and Short-Term Insomnia are
Caused by Identifiable Precipitants
Transient Insomnia
Short-Term Insomnia
 Lasts several days
 Consequence of acute stress
 Up to 3 weeks’ duration
 Major life stressors
or environmental changes
–
–
–
–
–
–
Unfamiliar sleep environment
Situational stress
Acute medical illness
Shift work
Jet lag
Caffeine, alcohol, nicotine, or
drug side effects
–
–
–
–
–
–
–
Hospitalization
Emotional trauma
Pain
Marriage
Divorce
Moving
Bereavement
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Chronic Insomnia Requires
a Thorough Evaluation
Symptoms
Treatment
Differential Diagnosis
Diagnosis
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Chronic Insomnia Is
Often Multifactorial
 Psychiatric illness(es)
 Primary sleep disorder(s)
 Medical illness(es)
 Medication(s)
Treat the underlying cause(s)!
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Empiric Treatment of Insomnia
Is Often Necessary
 Underlying causes of insomnia are often:
– Not apparent
– Not fully treatable
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Differential Diagnosis of
Chronic Insomnia
 Primary psychiatric disorders
 Medication-related
 Licit and illicit substances
 Medical disorders
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Differential Diagnosis of
Chronic Insomnia
 Restless Legs Syndrome (RLS) and
Periodic Limb Movement Disorder (PLMD)
 “Conditioned” insomnia
 Sleep schedule disorders
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Everybody with Chronic Insomnia
Must Practice Good Sleep Hygiene
 Standardize wake time
 Limit amount of time awake in bed
 Limit napping
 Remove clock from vision
 Avoid caffeine (after noon) and alcohol

(after 6 pm)
Avoid stressful activities in evening
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Psychiatric Disorders Are Present
in 40% of Those with Insomnia
Drug Abuse
4.2
Other Psychiatric Disorder
5.1
Alcohol Abuse
7.0
Dysthymia
8.6
Major Depression
14.0
Anxiety Disorders
23.9
No Psychiatric Disorder
59.5
0
10
20
30
40
50
60
% of Respondents
Ford DE, Kamerow DB. JAMA. 1989;262:1479-1484.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
All Psychiatric Disorders
Produce Insomnia
Mania > Schizophrenia >
Depression and Anxiety Disorders
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
% of Subjects
Sleep Disturbance Is the Most Common
Refractory Symptom in Treated MDD
50
45
40
35
30
25
20
15
10
5
0
Subthreshold
Threshold
SYMPTOMS
MDD = major depressive disorder.
Nierenberg AA, et al. J Clin Psychiatry. 1999;60:221-225.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia Related to Medications
 Antidepressants
 Stimulants
 Steroids, bronchodilators
 Decongestants
 Dopaminergic antagonists (akathisia)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia in Elderly Is Not Related
to Age, But to Medical Illness
 Cardiac: angina,



PND
Pulmonary: COPD,
coughing
GI: Nocturnal reflux
Musculoskeletal
pain
 Endocrine: Hypo/


hyperthyroidism,
diabetes, menopause
Neurologic:
Dementia,
Parkinson’s, CVA,
migraine
Urinary: Nocturia,
renal failure
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Licit Substances
 Caffeine
– Sleepiness can overcome stimulant
effects, but awakenings are common
 Alcohol
– Produces 3-4 hours of good sleep,
followed by increased wakefulness in
the second half of the night
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Restless Legs Syndrome (RLS) –
Diagnosis
Minimal Criteria
 Urge to move legs, usually with
uncomfortable leg sensations
 Onset or worsening of
symptoms at rest or inactivity,
such as when lying or sitting
 Relief with movement –
partial or total relief from
discomfort by walking or
stretching
Additional Features
 Sleep disturbance
 Involuntary leg movements
 Positive RLS family history
 Response to dopaminergic
therapy
 Worsening of symptoms in the
evening and at night
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prevalence by Age and Gender from
the REST Population-Based Survey
RLS Sufferers (n=116)
8
Prevalence (%)
All
6
Men
Women
4
2
0
20-29
30-39
40-49
50-59
60-69
70-79
80+
AGE GROUP (years)
Allen RP, et al. Arch Intern Med. 2005;165:1286-1292.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Pathophysiology of RLS





Idiopathic
Familial (30%-60%)
Iron Deficiency
Renal Failure
Peripheral
Neuropathy
 Rheumatoid Arthritis
 Medication-Induced


(especially SRIs)
Fibromyalgia
Pregnancy
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Iron Deficiency and RLS
 Reductions in 1) CSF ferritin and 2) substantia



nigra iron by MRI, transcranial ultrasound, and
on autopsy
Fe is a cofactor in the hydroxylation of tyrosine
into L-DOPA
Serum iron deficiency is present in a minority of
RLS patients
Iron repletion may be effective in iron-deficient
patients with RLS (ferritin <40)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Pharmacologic Treatment of
Moderate to Severe RLS
DOPAMINERGIC AGENTS
Pramipexole 0.125 – 1.0*,
Persistent sleep
disruption
Add sedative (e.g., trazodone, benzo, gabapentin)
*FDA-approved for RLS
Ropinirole* 0.5-4.0 mg q8pm
Partial response
Add gabapentin
or opiate
Non-response
Reassess
diagnosis
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Schedule Disorders
 Delayed Sleep Phase Syndrome
– Most common in adolescents
– Initial insomnia and difficulty awakening in AM
– Daytime sleepiness
 Advanced Sleep Phase Syndrome
– Most common in the elderly
– Early AM awakening
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Conditioned or
Psychophysiological Insomnia
 Begins with an acute insomnia and
is then maintained by negative
associations and anxiety regarding
sleep initiation (“insomnia phobia”)
as well as by poor sleep hygiene
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment of
Conditioned Insomnia
 Improve sleep hygiene
 Cognitive Behavioral Therapy
 Hypnotics intermittently or chronically,
if CBT fails
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Pharmacologic Interventions for
Primary Insomnia
 FDA-approved
– Nonselective BZ-receptor agonists
– Selective GABA-receptor agonists
– Melatonin-receptor agonists
 Non–FDA-approved
– Sedating antidepressants
– Sedating anticonvulsants
– Sedating antipsychotics
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Hypnotic Medications
Drug
Half-Life (hrs)
Doses (mg)
8-24
1, 2
Flurazepam (Dalmane®)
48-120
15, 30
Quazepam (Doral®)
48-120
7.5, 15
Temazepam (Restoril®)
8-20
7.5, 15, 22.5, 30
Triazolam (Halcion®)
2-4
0.125, 0.25
Zolpidem (Ambien®)
1.5-2.4
5, 10
Zolpidem ER (Ambien CR®)
2.8-2.9
6.25, 12.5
Zaleplon (Sonata®)
~1
5, 10
Eszopiclone (Lunesta®)
5-7
1, 2, 3
1-2.6
8
BENZODIAZEPINES
Estazolam (ProSom)
NONBENZODIAZEPINES
MELATONIN RECEPTOR AGONIST
Ramelteon (Rozerem)
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Fears Regarding BzRAs Lead to
Undertreatment of Insomnia
BENEFITS
FEARS
• Efficacy of medications
• Wide range of T1/2
• Fears of “addiction,” abuse
• Package label restrictions
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
No Evidence of Tolerance with 6 Months of
Nightly Use of Eszopiclone for Insomnia
Median Wake-Time
After Sleep Onset
60
60
40
50
50
40
30
20
*
*
*
*
*
*
Minutes
Minutes
Median Sleep Latency
30
20
10
10
0
0
1
2
3
4
Months
5
Eszopiclone
*p<0.005; †p<0.05; ‡p=0.07.
Krystal AD, et al. Sleep. 2003;26:793-799.
6
3 mg (n = 593)
†
1
†
†
‡
2
3
4
Months
†
†
5
6
Placebo (n = 195)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Current Status of BzRA Risks
in the Treatment of Insomnia





Motor vehicle accidents in elderly: long T1/2 agents
Hip fractures in elderly: long T1/2 agents?
Anterograde amnesia: T1/2-dependent
Abuse: rarely seen outside of drug abusers
Tolerance: no evidence from recent 12- and
26-week studies
 Rebound insomnia: depends upon dose, duration
of use, and speed of taper
Hemmelgarn B, et al. JAMA. 1997;278:27-31.
Cumming RG, Le Couteur DG. CNS Drugs. 2003;17:825-837.
Woods JH, Winger G. Psychopharmacology. 1995;118:107-115.
Krystal AD, et al. Sleep. 2003;26:793-799.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Antidepressants in the Treatment of Insomnia:
Mirtazapine, Trazodone, Amitriptyline, Doxepin
 Advantages: Little abuse liability
 Disadvantages: Probably not as effective
as BzRAs, daytime sedation, weight
gain, anticholinergic side effects, switch
into mania in bipolar disorder
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Atypical Antipsychotics in the Treatment of Insomnia:
Olanzapine, Quetiapine, Risperidone, Ziprasidone
 Advantages: Anxiolytic, mood stabilizing

in bipolar disorder, little abuse liability
Disadvantages: Less effective than
BzRAs, daytime sedation, weight gain,
risks of extrapyramidal symptoms and
glucose + lipid abnormalities
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Anticonvulsants in the Treatment of Insomnia:
Gabapentin, Topiramate, Tiagabine
 Advantages: Little abuse liability
 Disadvantages: Less effective than BzRAs,
cognitive impairment, daytime sedation
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Issues with Non-BzRA Hypnotics in the
Treatment of Insomnia (e.g., antidepressants,
anticonvulsants, antipsychotics)
 Paucity of short-term efficacy data
 Absence of long-term efficacy data
 Assumptions of lack of tolerance and
rebound insomnia are unsubstantiated
 Anecdotally less effective hypnotics than
BzRAs
 May have deleterious side effects
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Hypersomnia vs. Fatigue
 Hypersomnia
– Excessive daytime somnolence
(see algorithm, next slide)
 Fatigue
– Lack of energy, “tiredness”
– Multiple medical and psychiatric etiologies
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Differential Diagnosis of
Excessive Daytime Sleepiness
Inadequate
Sleep Time
Poor Sleep
Quality
 Voluntary restriction
 Shift work sleep
disorder
 Delayed Sleep Phase
Disorder
 Sleep apnea
 Periodic Limb
Movement Disorder
 Pharmacologic or
environmental
disturbances
Excessive
Sleep Drive
 Narcolepsy
 Idiopathic
Hypersomnia
 Medications
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Obstruction of the Airway =
Apnea
Site of upper airway
collapse
 Sleep apnea prevalence is 4% of males, 2% of females
 Risk factors include obesity, upper airway narrowing, sedatives
 Loud snoring, witnessed apneas, excessive daytime sleepiness
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prevalence of Obstructive Sleep
Apnea Syndrome (OSAS)
 Males = 4%
 Females = 2% (post-menopausal
prevalence rises to equal males)
Young T, et al. N Engl J Med. 1993;328:1230-1235.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment of OSAS
 Nasal Continuous Positive Airway


Pressure (CPAP)
Weight loss
Improve upper airway patency with nasal
steroids, surgery, dental device
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
When to Refer for Sleep Study?
 Suspicion of sleep apnea (loud snoring PLUS one
of the following):
–
–
–
–
Daytime somnolence
Witnessed apneas
Refractory hypertension
Refractory sleep complaints
 Abnormal behaviors or movements during sleep
 Unexplained excessive daytime sleepiness
 Refractory sleep complaints, particularly repetitive
brief awakenings
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Therapeutic Approaches to
Chronic Insomnia
 Insomnia is extremely common,



particularly among those with medical
and psychiatric illness
Potential underlying causes must be
assessed to optimize treatment
Insomnia can be both a symptom and
a disorder
The cause of insomnia is often
multifactorial
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Therapeutic Approaches to
Chronic Insomnia (cont’d)
 Risks of untreated insomnia must be


carefully assessed
Sleep hygiene and CBT should be
first-line treatments
Medications can be used intermittently
or, when necessary, chronically to treat
insomnia
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Therapeutic Approaches to
Chronic Insomnia (cont’d)
 Long-term treatment
– Regular reassessment of risks and benefits of
both insomnia and pharmacotherapy
– If discontinuing medication, use CBT and
carefully taper to minimize the return of
insomnia
– Consultation and/or polysomnography in
refractory insomnia is encouraged
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Evaluating and
Treating Comorbid
Sleep and Psychiatric
Disorders in Children
Daniel S. Lewin, PhD, D.ABSM
Director, Pediatric Behavioral Medicine Program
Associate Director, Pediatric Sleep Disorders Program
Children’s National Medical Center
Associate Professor of Psychiatry and Pediatrics
George Washington University School of Medicine
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosure
 Dr. Daniel S. Lewin has no financial
relationships over the past 12 months
with any commercial organizations
having a direct or indirect interest in the
subject matter of his presentation
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Outline
 Developmental changes in sleep
 Evaluating sleep and psychiatric disorders
 Treatment of common sleep disorders
associated with behavior problems and
psychiatric disorders
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Comorbid Sleep and
Psychiatric Disorders
 Bi-directional links between affective
disorders (depression and anxiety) and
sleep problems
– Serotonin and norepinephrine
– Hyperarousal and cognitive disinhibition
(rumination & worry)
 Shared or common phenotypes
– ADHD & signs of disordered sleep
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Change in Distribution of Sleep
Stages – Birth Through Adolescence
16
NREM
REM
Total Sleep Time (Hrs)
14
12
10
8
6
4
2
0
Term
1 mo.
6 mo.
12 mo. 2 yrs.
Anders T, et al. In: Ferber R, Kryger M, eds. Principles and Practice
of Sleep Medicine in the Child. Philadelphia: WB Saunders, 1995, pp. 7-18.
5 yrs.
10 yrs. 16 yrs.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Estimated Norms for
24-Hour Sleep Duration
POLL DATA
(NSF ’05 & ’06)
POPULATION DATA
Iglowstein ’03
(Switzerland)
Infants (3-11 mo.)
12.7
14.2-13.9 (1.7)
Toddlers (12-35 mo.)
11.7
13.5-12.5 (1.2)
Pre-K and K (3-5 yrs.)
10.4
12.5-11.4 (0.9)
School-aged (6-10 yrs.)
9.5
11-9.9 (0.6)
11-15 yrs.
8.4-7.2
9.6-8.1 (0.7)
16-18 yrs.
7.2-6.9
AGE GROUP
National Sleep Foundation. Sleep in America polls, 2005 & 2006. Available at:
http://www.sleepfoundation.org/site/c.huIXKjM0IxF/b.2417353.
Iglowstein I, et al. Pediatrics. 2003;111:302-307.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Child and Adolescent
Sleep Patterns
African American Children – Ages 6-18 (n=42)
Total Sleep Time (min)
490
480
470
460
450
440
430
420
Sun
Mon
Tue
Wed
Thu
Fri
Sat
DAY
Alfano C, et al. Sleep. 2007;30(abstract suppl):A96.
Presented at: APSS 2007, Minneapolis, MN.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Drive
SLEEP LOAD
WAKE
Circadian
Cycle
ALERTING
SIGNAL
9 AM
3 PM
Day - awake
NHLBI Sleep Academic Award, Gerald Rosen.
9 PM
SLEEP
3 AM
9 AM
Night - asleep
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Assessment Techniques –
The Clinical Interview
 Thorough history
– Observation of parent-child interactions
– Sleep history: B.E.A.R.S
– Other sleep disorders
– Medical history (GERD, pain)
– Developmental history
– Psychiatric history
– Family (psych history, schedule, marital,
attachment)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
The Sleep Habits Assessment
Bedtime
EDS
Awakenings
Regularity Snoring
 Call-outs
 Partial
 Schedule
 Age
(Excessive Daytime
Somnolence)
 Routine
 Hyperactivity
 Resistance  Irritability
 Fears
 Difficulty
waking
arousal
 Restlessness
Adapted from: Mindell JA, Owens JA. A Clinical Guide to Pediatric Sleep:
Diagnosis and Management of Sleep Problems. Philadelphia: Lippincott,
Williams & Wilkins, 2003.
 Volume
 Pauses
 Periodicity
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Questionnaires
 Pediatric Sleep Questionnaire (OSA 6-18)
– Chervin RD, et al. Sleep Med. 2000;1:21-32.
http://www.saintpatrick.org/images/sleep_questionnaire.pdf
 The Cleveland Adolescent Sleepiness
Questionnaire (12-18)
– Spilsbury JC, et al. J Clin Sleep Med. 2007;3:603-12.
 Children’s Sleep Habits Questionnaire (6 to 12)
– Owens J, et al. Sleep. 2000;23:1043-51.
 Epworth Sleepiness Scale (Adult)
– Johns MW. Sleep. 1991;14:540-5.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
When to Order a Sleep Study
 Snoring +
– Gasps and pauses in respiration
– Academic or attention problems
– Other sleep disorders
 Movement-related sleep disorder (RLS/PLMD)
 Rule out narcolepsy, idiopathic hypersomnia
 Persistent and treatment-resistant sleep
disturbances
 Normative values for nap studies (MSLT) are
unreliable in children <10 years
RLS/PLMD = restless legs syndrome/periodic limb movement disorder;
MSLT = Multiple Sleep Latency Test.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Psychiatric/Behavioral
Questionnaires
 Child Behavior Checklist (general behavior problems)
http://www.aseba.org/
 Children’s Depression Inventory
http://www.pearsonassessments.com/tests/cdi.htm
 Vineland Adaptive Behavior Scale (developmental status)
http://ags.pearsonassessments.com/group.asp?nGroupInfoID=a3000
 Connors ADHD Rating Scales
http://www.pearsonassessments.com/tests/crs-r.htm
 BRIEF (Executive function and ADHD)
Gioia GA, et al. Neuropsychol Dev Cogn Sect C Child Neuropsychol. 2000;6:235-8.
 SCARED (Anxiety)
Birmaher B, et al. J Am Acad Child Adolesc Psychiatry. 1997;36:545-53.
http://www.wpic.pitt.edu/research/city/Family/Anxiety/OnlineAnxietyScreen_files/PDF%20Files/Sc
ared%20Parent-final.pdf
 Visual Analogue Scales


← 100 mm →
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Child Behavior Checklist
 Factor analyzed scale
 Over 1,000 Medline citations
 Normative values for girls, boys, and
3 age groups
 4 competence scales
 3 problem summary scales
 8 problem subscales
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Signs of Disordered Sleep
in the Child
 Excessive time spent





falling asleep
Repeated awakenings
Difficulty waking in the
morning
Impaired daytime alertness
Parental sleep loss
Sleep-related impairment
of the parent-child
relationship
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Pediatric Sleep Disorders
Age
range
(yrs)
Category
Disorder
Prevalence
Insomnia
Psychophysiological insomnia (307.42)
Behavior insomnia of childhood (V69.5)
- Sleep-onset association type
- Limit-setting type
~20%-50%
10%-30%
~6-18
0.5-~8
0.5-~3
~1-~8
Sleep-Related
Breathing
Primary sleep apnea of infancy (770.81)
Obstructive sleep apnea, pediatric (327.23)
Congenital central alveolar hypoventilation
(327.25)
0.5% (healthy)
~3%-5%
<0.01%
0-0.2
0.2-18
Birth
Hypersomnia
Narcolepsy (347)
Kleine-Levin syndrome (327.13)
Behaviorally induced insufficient sleep
syndrome (307.44)
>0.02%
>0.01%
?
?
~14
?
American Academy of Sleep Medicine. ICSD-2. Westchester, IL: AASM, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Pediatric Sleep Disorders (cont’d)
Category
Disorder
Prevalence
Age
range
(yrs)
Circadian Rhythm
Sleep Disorder
Delayed sleep phase syndrome
Advanced sleep phase syndrome
>16%
?
>12
0.5-6
Parasomnias
Confusional arousals (327.41)
Sleep walking (307.46)
Sleep terrors (307.46)
Sleep enuresis (788.36)
17.5%
17%
1%-6.5%
By age
<3-13
<3-18
<3-18
>4
Sleep-Related
Movement
Disorder
Restless legs syndrome (333.99)
Periodic limb movement disorder (327.51)
Sleep-related rhythm movement disorder
(327.59)
<16%
?
?
?
3%-6%
>0.5
American Academy of Sleep Medicine. ICSD-2. Westchester, IL: AASM, 2005.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Child Behavior Checklist – Between-Group
Differences, OSA vs. Control, 6-10 years
60
Comparison (n=37)
OSA (n=76)
T-Score
55
*
*
*
*
50
45
m
So
ic
at
al
ci
So
ep
on
si
n
aw
dr
ith
/D
nx
s
re
gg
W
A
A
n
io
nt
tte
A
g
in
iz
al
rn
te
Ex
g
in
iz
al
rn
te
In
l
ta
To
*P<0.006, Bonferroni correction
Unpublished data.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Mean Rates of CBCL Sleep Items
Very true
1
Sleep
Often true
0.5
Never
0
Nightmares
Anxious
Overtired
Alfano CA, et al. Sleep Med. 2006;7:467-73.
Control
Sleeps <
Sleeps >
Talks/walks
Trouble
sleeping
Wets bed
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
% Sleep Disorder Symptoms
Sleep Disorder Symptoms in Children
With Two or More Psychiatric Diagnoses
Combined
Child
Adolescent
50
45
40
35
30
25
20
15
10
5
0
B
SD
as
ni
es
ar
m
ht
ig
a
in
m
so
ra
Pa
N
m
so
In
SD
S
ED
B
Hall T, et al. Sleep. 2006;29(abstract suppl):A333.
Presented at: APSS 2006, Salt Lake City, UT.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep-Related Anxiety vs. Fear
 Bedtime and sleep-related fears are normal


and state-related or transient
Sleep-related anxiety is a marker of
psychopathology and is a more stable
condition that is also present during the day
Early sleep disruption predicts later
emergence of anxiety disorders and
substance abuse (Gregory & Connor, 2002)
Gregory AM, O'Connor TG. J Am Acad Child Adolesc Psychiatry. 2002;41:964-71.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Hypothesized Links –
Sleep and ADHD
 H1 – Sleep problems may account for symptoms of
inattention and hyperactivity in 10%-20% of children
diagnosed with ADHD
– Chervin et al, 2002; Gozal, 1998; Picchietti et al, 1998;
O’Brien et al, 2003; Cortese et al, 2006
 H2 – ADHD is a disorder of HYPO-VIGILANCE
– Rubia K et al, 1999; Weinberger W et al, 1993; Lecendreaux M,
et al, 2000
 H3 - Underlying abnormalities in sleep/wake
mechanisms are associated with ADHD
Chervin RD, et al. Sleep. 2002;25:213-8; Chervin RD, et al. Pediatrics. 109:449-5;
Gozal D. Pediatrics. 1998;102(3 Pt 1):616-20; Picchietti DL, et al. Mov Disord.
1999;14: 1000-7; O’Brien LM, et al. Pediatr Res. 2003;54:237-43; Cortese S, et al.
Sleep. 2006;29:504-11; Rubia K, et al. Behav Brain Res. 1998;94: 25-32; Weinberger
DR. Neurosciences. 1993;5:241-53; Lecendreaux M, et al. J Child Psychol
Psychiatry. 2000;41:803-12.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
MSLT Results for ADHD and Control Groups
at Each Nap (Mean Sleep Latency ± SEM)
Sleep Latency During MSLT
MSLT = Multiple Sleep Latency Test
Golan N, et al. Sleep. 2004;27:261-6.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
A Few Key Principles
 A tired child does not look



like a tired adult
Neurobehavioral functioning
should be a factor in
intervention decisions
Prior to age 10 children are
unreliable reporters of
internal states
There is high comorbidity
of sleep and psychiatric
disorders in children
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Behavioral Insomnias of
Childhood
 Occur in as many as





50%, and 30% tell
pediatricians about
the problem
Difficulty falling asleep
Bedtime resistance
Difficulty staying asleep
Poor sleep quality
Too little sleep for
parents and/or children
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
The Letting Down of Vigilance
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Behavioral Insomnias of
Childhood
 Sleep-Onset Association
Disorder
– Prevalence: 25%-30%
– Age group: 6-36 months
– Clinical features
• Delayed sleep onset &
nighttime awakenings
• Sleep onset becomes
associated with
exogenous cues
• Sleep onset at bedtime
or the middle of the
night will not occur
w/out cue
 Limit-Setting Sleep Disorder
– Prevalence: 25%-30%
– Age group: 18-60 months
– Clinical features
• Delayed bedtime
• Parents reinforce
undesirable behavior
at bedtime
• Inconsistent limit-setting
• Otherwise normal
nocturnal sleep
American Academy of Sleep Medicine. ICSD-2. Westchester, IL: AASM, 2005.
Mindell JA. J Pediatr Psychol. 1999;24:465-81.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Case Study 1 – Carl
 24.5-month-old boy
 Presenting complaint
– Erratic sleep/wake schedule
– Sleeps with mother in her bed every night
– Difficulty weaning
 History
– Uncomplicated vaginal delivery to a 38-year-old
– History of colic and GERD
– Normal development
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
2.5 years
N = Nursing
= Irritable
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Targets of Treatment
 Bedtime Resistance
– Curtain calls
– Nighttime fears
– Bed/crib aversion
– Crying/tantrums
 Nocturnal Awakenings
– Nighttime call-outs
– Crying
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Behavioral Insomnias of
Childhood – Treatment
 Identify and eliminate reinforcers
or cues that delay an independent
wake-sleep transition
 Establish appropriate bed times
 Establish appropriate bedtime
routines
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Behavioral Insomnias of
Childhood – Treatment
 Extinction and its Variations
– Simple extinction (“Cry it out” – cold turkey)
• Ignore child’s attention seeking/inappropriate behavior
• Immediate withdrawal of parent, bottle, holding, breast feeding
– Graduated extinction (“Ferberize”): incremental withdrawal
of parent involvement
• Increase visit intervals
• Decrease duration of visits
 The Bedtime Pass (Moore et al, 2007)
– Child-controlled single visitation
 Fading Approaches
– Graduated increase in proximity
– Graduated decrease in quality of interaction
Moore BA, et al. J Pediatr Psychol. 2007;32:283-7.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Carl’s Treatment
 Decrease frequency and duration of nursing
 Limit sleep to own bedroom
 Fade parents involvement in wake-to-sleep
transition
 Involve father in bedtime ritual
 Introduce transitional object
 Limit-setting during day
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Autism and
Developmental Disorders
 Sleep problems are particularly common
among these populations
– Anxiety
– Impaired social perception
– Impairment in learning routines
 Same treatment principles apply
– Pace of approach should be modified
– Applied behavioral analysis
• Response cost (delaying “sleep” as reward)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Bedtime Transition Cues
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Psychophysiological Insomnia in
Children – Treatment
 Psychophysiologic insomnia in children has not
been adequately studied
 Treatment approaches do not differ from those that
have been established for adults
–
–
–
–
–
Stimulus Control
Sleep Restriction
Sleep Hygiene Training
Cognitive Therapy
Relaxation
 Developmental and mental health factors must be
considered
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Hygiene
 Regular bed and wake times
 Eliminate caffeine
 Eliminate stimulating behavior before bedtime
 No electronic media within an hour of


bedtime
Quiet reading/snuggling
Establish and early evening worry time
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Relaxation Training
 Decrease somatic and cognitive arousal
 Distraction
– Deep breathing
– Somatic relaxation (e.g., progressive
muscle relaxation
– Cognitive techniques (guided imagery)
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Obstructive Sleep Apnea
Syndrome (OSAS)
 Pauses in breathing during sleep
 How common is it?
– 1.1%-2.9% of 4-5 year-olds
– 18% of children w/ behavior & academic problems
(Gozal, 1998)




Causes: obstructed or narrow upper airway
Signs – Snoring, snorting, gasping, breathing pauses
Effects: Decreased oxygen and sleep disruption
Daytime effects: attention, mood, impulsivity
(Beebe, 2006)
Gozal D. Pediatrics. 1998;102(3 Pt 1):616-20.
Beebe DW. Sleep. 2006;29:1115-34.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
OSA Treatment
 Surgical interventions
– Adenoid and/or tonsillectomy
– UPPP (uvulopalatopharyngoplasty) – Adults
– Mandibular advancement
– Tracheostomy
 Nasal CPAP/BiPAP
 Palatal expansion
 Weight loss
 Sleep positioning
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Case Study 2 – Insomnia









13-year-old female
SOL 1-1.5 hours, no problems with WASO
Falls asleep with parent
Periodic use of Benadryl and melatonin
Limb discomfort at bedtime
Caffeine 1-2 times/week
Difficulty waking >5 days/week
Mild occasional snoring
Modified Epworth = 11; CDI = 5; SCARED =
80th%
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
9
9.75
1.5
9
10
8
8.25
8.5
8
10
10
9.5
1.5
1
7
8
Average total sleep time: 9.2 hours
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Case Study 2 – Treatment







Sleep education
Address worry at bed time (worry diary, psychotherapy)
Consistent sleep environment
Stimulus Control
TIB restricted to 9 hours: 9-6 weekdays & 10-7 weekends
Eliminate naps >15 min
Relaxation Therapy (deep breathing, guided imagery,
progressive muscle relaxation)
 Rule out restless legs syndrome (iron panel)
 Eliminate caffeine use
 Melatonin @ 6:00 pm
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Case Study 3 – Delayed Sleep
Phase Syndrome
 16-year-old Hispanic female
 Maintaining A/A- grade average
 Single parent home, 2 younger siblings
 Generalized Anxiety Disorder
 Chronic fatigue and possible dysthymia
 Shy and socially anxious
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
7.5
4
4.5
8.5
1.5
4
4.5
3.5
4.5
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Delayed Sleep Phase Syndrome
(DSPS) – Assessment
 Evaluate motivation (secondary gain)
 Evaluate psychopathology
 Sleep log & actigraphy
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
DSPS Treatment
 Contract for at least 4 weeks
 Modify involvement in highly rewarding
activities
 Chronotherapy (phase – advance/delay;
acute sleep debt)
 Light and temperature
 Melatonin
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Treatment
 Fixed sleep schedule w/ weekend flexibility
 Chronotherapy – gradual phase advanced
 Eliminated caffeine
 Light box 1 hour in AM
 Stimulus Control
 Referred for psychotherapy
 Melatonin
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
When to Use Sleep-Promoting
Medications







Pain
Acute trauma?
Major life stressor
Injury risk and safety
issues
Severe developmental
disability
Recurrent high-risk
parasomnias
?Short term use in
treatment-resistant
insomnia?
Percentage of Physicians Prescribing
Specific Medications for Sleep Problems
30
25
Antihistamine
20
Alpha Agonist
15
Benzodiazepines
Chloral Hydrate
10
Antidepresant
5
0
0 to 2
3 to 5 6 to 12
Owens JA, et al. Pediatrics.
2003;111(5 Pt 1):e628-35.
13 +
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Summary
 Sleep and psychiatric disorders have similar
phenotypes
 Child psychiatry evaluations should include
assessment of
– Insomnia
– Insufficient sleep
– Sleep disordered breathing
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
THANK YOU
Daniel S. Lewin, PhD, D.ABSM
Children’s National Medical Center,
Washington, DC
[email protected]
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Evaluation and
Management of Insomnia
in Home-Dwelling
Older Persons
W. Vaughn McCall, MD, MS
Chair and Professor, Department of Psychiatry
and Behavioral Medicine
Wake Forest University School of Medicine
Winston-Salem, North Carolina
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosures
 Dr. W. Vaughn McCall has received grants
or research support from GlaxoSmithKline,
sanofi-aventis, and Sepracor. He has been
a consultant for Sepracor and a speakers
bureau member for GlaxoSmithKline and
Sepracor.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Is Important
Throughout the Life Cycle
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep and Age
Total Sleep in Minutes
700
600
500
Total time in bed
400
Awake in bed
NREM stage 1
300
REM
200
NREM stage 2
100
NREM δ
10
20
30
40
50
60
70
80
Age in Years
Williams RL, et al. EEG of Human Sleep: Clinical Applications. 1974, p. 91.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
The Prevalence of Obstructive Sleep
Apnea (OSA) Increases With Age
Event Index (Per Hour of Sleep)
Habitual Snorers (19.0%)
100
Habitual Snorers (%)
90
80
70
60
Men 24.1%
50
40
30
20
Women 13.8%
10
>75
71-75
66-70
61-65
56-60
51-55
46-50
41-45
36-40
31-35
26-30
21-25
16-20
11-15
6-10
0
30
AHI ≥10
OAHI >10
25
AHI ≥10 plus clinical
symptoms of OSA
20
15
10
5
0
20-44
Age (Years)
Parati G, et al. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1671-R1683.
Stradling JR, et al. Thorax. 2004;59:73-78.
Ferini-Strambi L, et al. Minerva Med. 2004;95:187-202.
45-64
≥65
Age Groups
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
OSA and Depressive Symptoms
 Mild OSA is associated with depressive symptoms1
 Treatment of OSA is associated with improvement of
depressive symptoms (sometimes—4 out of 7 studies)2
Comparison of Clinical and Laboratory Measures in
Men and Women With Obstructive Sleep Apnea
Men
Women
Total
92
29
121
Age, y
54.7 ± 14.3
54.4 ± 13.5
54.7 ± 14.1
RDI, no./h
58.0 ± 25.9
50.7 ± 30.7
56.2 ± 27.2
ESS score
13.2 ± 6.0
12.0 ± 5.3
12.9 ± 5.8
BDI score*
8.1 ± 6.7
15.4 ± 10.5
9.9 ± 8.3
No.
Data are presented as mean ± SD unless otherwise indicated.
BDI, Beck Depression Inventory; ESS, Epworth Sleepiness Scale; RDI, respiratory disturbance index.
*Men different from women, p<0.01.
McCall WV, et al. J Clin Sleep Med. 2006;2:424-426.
Saunamäki T, et al. Acta Neurol Scand. 2007;116:277-288.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
OSA and Dementia
 OSA is linked to cognitive impairment, defined as 1.5 SDs or more from the
sample mean on MMSE or Trails B, especially in those with the APOE 4 allele
 Treatment of OSA is associated with improvement of cognition
Association Between Sleep-Disordered Breathing and Clinically Significant
Cognitive Impairment (>1.5 Standard Deviations [SDs] from Mean Score)
Odds Ratio (95% Confidence Interval)
Cognitive Measure
Unadjusted
Multivariate Adjusted*
Mini-Mental State Examination
AHI (per SD)
1.5 (1.1 – 2.0)
1.4 (1.03 – 1.9)
AHI ≥30
4.0 (1.8 – 9.1)
3.4 (1.4 – 8.1)
SaO2 <80%
2.4 (1.0 – 5.6)
2.7 (1.1 – 6.6)
CAI (per SD)
1.3 (1.1 – 1.6)
1.4 (1.1 – 1.7)
AHI (per SD)
1.2 (0.9 – 1.6)
1.1 (0.8 – 1.5)
AHI ≥30
1.7 (0.7 – 4.2)
1.2 (0.5 – 3.2)
SaO2 <80%
1.2 (0.5 – 3.0)
1.2 (0.5 – 3.2)
CAI (per SD)
0.6 (0.2 – 2.0)
0.5 (0.2 – 1.6)
Trail Making Test Part B
*Adjusted for age, education, sex, and selective serotonin reuptake inhibitor use. AHI, apnea-hypopnea index;
SD, standard deviation; SaO2, blood oxygen saturation; CAI, central apnea index.
Spira AP, et al. J Am Geriatr Soc. 2008;56:45-50.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Disturbance and
Institutionalization
Nursing Home Placement by Insomnia
Males
6
5
4
3
2
1
0
0
1-3
4-14
15-42
Complaint Nights
Pollak CP, et al. J Geriatr Psychiatry Neurol. 1991;4:204-210.
Pollak CP, et al. J Community Health. 1990;15:123-135.
Assigned to a Nursing Home (%)
Assigned to a Nursing Home (%)
Nursing home placements represent percent of the sample
permanently assigned to a nursing home over a 3.5-year follow-up period
Females
6
5
4
3
2
1
0
0
1-3
4-14
15-42
Complaint Nights
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
What Is Insomnia?
 Problems with falling asleep, staying asleep,
or unrefreshing sleep leading to:
– Fatigue
– Concentration problems
– Irritability
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Epidemiology of Insomnia
 57% of older persons report some sort of

1Foley
2Foley
chronic sleep disturbance1
Annual incidence rate of 5% for chronic
insomnia in the elderly2
DJ, et al. Sleep. 1995;18:425-432.
DJ, et al. Sleep. 1999;22(suppl 2):S366-S372.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Epidemiology of Insomnia
 57% of older people report some sort of chronic sleep disturbance
 Annual incidence rate of 5% for chronic insomnia in the elderly
Prevalence of Chronic Sleep Complaints in Selected Subpopulations of Participants: EPESE 1982
Type of Sleep Problem
Trouble
falling
asleep
Awakes
during
night
Awakes
too
early
Naps
during
day
Awakes
not
rested
Difficulty
initiating or
maintaining
sleep
Insomnia
Any
chronic
complaint
All participants
n=9,282 (100%), average age=74.0
19.2
29.7
18.8
24.6
12.7
42.7
28.7
56.9
Not depressed*
n=6,994 (75%), average age=73.8
13.2
24.9
14.3
22.1
8.7
36.1
21.9
50.9
And no physical limitation
n=2,607 (28%), average age=72.0
10.0
18.0
9.8
14.5
5.6
27.7
16.6
39.4
And no respiratory symptom
n=2,207 (24%), average age=72.0
9.3
16.8
9.0
13.4
5.1
25.8
15.4
37.2
And excellent SPHS
n=679 (7%), average age=71.7
7.4
16.5
7.4
11.9
2.7
24.3
13.4
33.9
And no other risk factors†
n=175 (2%), average age=71.6
4.0
13.9
3.5
7.5
2.3
17.9
7.5
26.6
Population
*And not using an anxiolitic/barbiturate medication.
†Excludes those with any of the 7 selected chronic conditions and those taking OTC medications.
Foley DJ, et al. Sleep. 1995;18:425-432.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Normal Aging of Sleep
vs Insomnia
 Comparison of 72 older adults with or without sleep complaints
– 42 poor sleepers
– 30 normal controls
 Community residents
–
–
–
–
Mean age, yr (SD): 66.8 (5.2)
Female: 64%
Married: 65%
Unemployed: 67%
 Assessments
–
–
–
–
Sleep
Mood
Medical illness
Lifestyle
Morin CM, Gramling SE. Psychol Aging. 1989;4:290-294.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Normal Aging of Sleep vs Insomnia:
Comparison of Sleep Measures
Most Sleep Measures Were Significantly Different*
Poor sleepers
mean (SD)
(n=42)
Good sleepers
mean (SD)
(n=30)
p
35.9 (25.8)
15.1 (19.5)
<0.01
2.8 (1.3)
1.2 (0.6)
<0.001
Wake-time after sleep onset (min)
59.7 (31.0)
15.0 (11.4)
<0.001
Total nocturnal sleep (min)
345.7 (73.8)
387.3 (82.5)
<0.05
Total sleep time/24 h (min)
377.1 (80.5)
412.9 (83.6)
NS
78.0 (8.4)
92.3 (6.0)
<0.001
Sleep
Sleep-onset latency (min)
Number of awakenings
Sleep efficiency (%)
*Mean age (SD) of the entire sample: 66.8 yr (5.2).
Morin CM, Gramling SE. Psychol Aging. 1989;4:290-294.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Normal Aging of Sleep vs Insomnia:
Comparison of Mood Measures
Mood Measures Were Significantly Different
Poor
sleepers
mean (SD)
Good
sleepers
mean (SD)
p
Depression (BDI)
10.9 (7.1)
6.4 (5.3)
<0.01
State anxiety (STAI)
38.7 (10.6)
32.3 (9.6)
<0.05
Trait anxiety (STAI)
43.2 (10.5)
34.6 (10.3)
<0.01
Mood
BDI=Beck Depression Inventory; STAI=State-Trait Anxiety Inventory.
Morin CM, Gramling SE. Psychol Aging. 1989;4:290-294.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Disturbances in Older
Persons: Underlying Causes
 Fragmented nocturnal sleep is a significant
cause of daytime sleepiness in older persons
– Continuity of both sleep and wakefulness is
disrupted
– More likely to be chronic
 Insomnia may be caused by or related to
coexisting conditions
Carskadon MA, et al. Neurobiol Aging. 1982;3:321-327.
Martin J, et al. Clin Psychol Rev. 2000;20:783-805.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
What Is the
Differential Diagnosis
of Insomnia in
Older Persons?
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Primary Sleep Disorders
Associated with Insomnia
 Primary insomnia1
 Breathing-related sleep disorder1
 Circadian rhythm sleep disorder1
 Parasomnia1
 Obstructive sleep apnea2
 Restless legs syndrome2
 Periodic limb movement disorder2
1. American Psychiatric Association. DSM-IV-TR. 2000:597-661.
2. Insomnia in Primary Care: Overcoming Diagnostic and Treatment Variables. 2004.
Available at: www.postgradmed.com/asr/insomnia/asr_insomnia.pdf. Accessed
January 19, 2006.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Apnea and Periodic Leg Movements
of Sleep in Prediction of Sleep Complaints
Polysomnography in 100 Seniors ≥65 years
70
58
Subjects (%)
60
50
40
34
30
20
10
0
Sleep Apnea
PLMS
…but the presence of sleep apnea and PLMS did not correlate
with subjective sleep complaints
Dickel MJ, Mosko SS. Sleep. 1990;13:155-166.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia, Hypnotic Use,
and Risk of Falls
Risk of Falls in 34,163 Nursing Home Residents ≥65 years
Insomnia
No Insomnia
n=259
Hypnotic
No hypnotic
1.32 (1.02-1.70)
1.55 (1.41-1.71)
n=1,890
Hypnotic
1.11 (0.94-1.31)
n=632
No hypnotic
1 (ref)
n=31,391
0
0.5
1
1.5
2
Odds Ratio (95% Confidence Interval)
Models controlled for age, sex, functional status, cognitive status, intensity of resource utilization, illness burden,
number of medications, emergency room visits, new admission.
Avidan AY, et al. J Am Geriatr Soc. 2005;53:955-962.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Have Behavioral
Treatments
Been Tested in
Older Persons?
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Exercise Improves
Sleep Parameters
Baseline
Posttest
p=0.007
p=0.047
7.5
28.4
26.1
23.8
25
20
15
14.6
10
Sleep Duration (hr)
Sleep Onset Latency (min)
30
7.0
6.5
6.0
6.0
5.0
0
4.5
n=20
King AC, et al. JAMA. 1997;277:32-37.
Control
n=23
6.0
5.8
5.5
5
Exercise
6.8
Exercise
Control
n=20
n=23
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Behavioral and Pharmacologic Therapies
Are Effective Alone and in Combination
Posttreatment*
Sleep Diary
80
70
60
50
40
30
20
10
0
CBT
n=18
PCT
n=20
Combined PBO
n=20
n=20
Condition
Time Awake After Sleep Onset (min)
Time Awake After Sleep Onset (min)
Pretreatment
Polysomnograph
80
70
60
50
40
30
20
10
0
CBT
n=18
PCT
n=20
Combined
n=20
PBO
n=20
Condition
*Sleep diary recording during final 2 treatment weeks; EEG on days 5 and 6 of treatment.
CBT=cognitive behavioral therapy; PCT=pharmacotherapy with temazepam; PBO=placebo.
Morin CM, et al. JAMA. 1999;281:991-999.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Melatonin Treatment:
Garfinkel et al
 12 elderly subjects with insomnia,
mean (SD) age: 76 (8) years
– All with below-normal or delayed nightly peak
excretion of the main melatonin metabolite
 Randomized, double-blind crossover study
– 3 weeks of 2-mg controlled-release melatonin
– 1 week of washout
 Actigraphy
– 3 weeks of placebo treatment
Garfinkel D, et al. Lancet. 1995;346:541-544.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Melatonin Treatment:
Garfinkel et al (cont’d)
Placebo
Melatonin
p
Sleep efficiency, %, mean (SE)
75 (3)
83 (4)
<.001
Sleep latency, min, mean (SE)
33 (7)
19 (5)
.088
Wake-time after sleep onset, min,
mean (SE)
73 (13)
49 (14)
<.001
Total sleep time, min,
mean (SE)
352 (19)
365 (20)
.49
Garfinkel D, et al. Lancet. 1995;346:541-544.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Conclusion
 Melatonin replacement therapy effectively
improved sleep quality
Garfinkel D, et al. Lancet. 1995;346:541-544.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Eszopiclone 1 mg or 2 mg in the
Treatment of Insomnia in Older Persons
-Study 1-
 Study objectives
– Evaluate safety and efficacy of eszopiclone (ESZ) in
older persons with insomnia
 Patient population
– 231 older persons (ages 64-85 y)
– Suffering from primary, chronic insomnia
 Study design
– ESZ 1 mg or 2 mg or placebo was administered once
nightly over 2 weeks
Scharf M, et al. Sleep. 2005;28:720-727.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Study Results
 Eszopiclone (ESZ) 1 mg was effective for sleep


induction
ESZ 2 mg demonstrated significant improvement
over placebo in sleep onset, measure of sleep
maintenance, sleep duration, and sleep quality
Improvements in next-day assessments
(morning sleepiness, daytime alertness, ability
to function) from baseline were noted with
ESZ 2 mg, and napping was reduced
Scharf M, et al. Sleep. 2005;28:720-727.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Eszopiclone 2 mg in the Treatment of
Insomnia in Older Persons
-Study 2 Study objectives
– Evaluate safety and efficacy of eszopiclone (ESZ) in older persons with
insomnia
 Patient population
– 264 older persons
– Suffering from primary, chronic insomnia
 Study design
– ESZ 2 mg or placebo was administered once nightly over 2 weeks
– Efficacy endpoints were assessed through polysomnography (latency to
persistent sleep, sleep efficiency, number of awakenings)
– Patient-reported data were collected via interactive voice response in the
morning and evening
– Quality of life was also assessed through the Insomnia Severity Index and
SF-36 (a short-form measure of generic health status)
McCall WV, et al. Curr Med Res Opin. 2006;22:1633-1642.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Latency to Persistent Sleep
(Polysomnography)
Median Sleep Latency (min)
60
Placebo
ESZ 2.0 mg
50
***p<0.0001 vs placebo
40
30
20
***
***
***
10
0
Baseline
Overall period
McCall WV, et al. Curr Med Res Opin. 2006;22:1633-1642.
Night 1
Night 14
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Wake After Sleep Onset
(Polysomnography)
120
Placebo
ESZ 2.0 mg
Median WASO (min)
110
*p<0.05 vs placebo
100
90
*
80
*
70
60
50
Baseline
Overall Period
McCall WV, et al. Curr Med Res Opin. 2006;22:1633-1642.
Night 1
Night 14
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Napping^
Number of Naps
(Median)
5
*p<0.05
4
3
*
2
1
0
Placebo
ESZ 2.0 mg
Total Nap Time (Minutes)
(Median)
100
90
80
70
60
50
40
30
20
10
0
p=NS
Placebo
ESZ 2.0 mg
^Patients were encouraged not to nap in this study.
These numbers represent data from patients who napped and represents values from overall double-blind period.
Approximately 47% of patients in each group napped during the study.
McCall WV, et al. Curr Med Res Opin. 2006;22:1633-1642.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Ramelteon 4 mg or 8 mg in
Older Persons with Insomnia
 Study objectives
– Assess efficacy of ramelteon in treating insomnia in
older persons (aged 64-93 yrs)
 Patient population
– 829 outpatients with primary insomnia
 Study design
– Subjects received ramelteon 4 mg or 8 mg or placebo
for 35 nights
– Sleep diaries were used to assess efficacy
Roth T, et al. Sleep Medicine. 2006;7:312-318.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Study Results
 Both 4 mg and 8 mg of ramelteon reduced patientreported sleep latency compared to placebo
 No rebound insomnia during posttreatment
Roth T, et al. Sleep Medicine. 2006;7:312-318.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Zolpidem Tartrate Extended-Release
6.25 mg in Older Persons With Insomnia
 Patient population
– Outpatients (≥65 years)
– Primary insomnia
– N=205
 Study design
– Double-blind, randomized, parallel-group
– 3-week comparison of zolpidem tartrate
extended-release 6.25 mg and placebo
Walsh JK, et al. Am J Geriatr Psychiatry. 2008;16:44-57.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Study Results
 Zolpidem tartrate extended release 6.25 mg


decreased wake time after sleep onset for the
first 6 hours during the first 2 nights and the
first 4 hours after 2 weeks of treatment
Superior to placebo on objective measures
(polysomnography) of sleep induction
Superior to placebo on the patient reported
global impression aid to sleep
Walsh JK, et al. Am J Geriatr Psychiatry. 2008;16:44-57.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Summary
 Behavioral and pharmacologic approaches are
effective for management of insomnia in older
persons
 Insomnia is a significant problem with potentially
severe consequences in older persons
 Particular attention is needed to identify and
address underlying medical or psychiatric coexisting
conditions
 Both behavioral and pharmacologic treatments are
effective in this population
Morin CM, et al. JAMA. 1999;281:991-999.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Conclusions:
Key Areas Needing Work
 Placebo-controlled studies of hypnotics in



older persons for periods longer than 2
weeks
Studies of sedating antidepressants
(doxepin) in older patients
Controlled studies in nursing home patients
with sleep problems
Sophisticated measures of daytime function
and adverse events as a result of hypnotics
in older patients
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Anxiety and
Insomnia in Women
Naomi M. Simon, MD, MSc
Associate Director
Center for Anxiety and Traumatic Stress Disorders
Massachusetts General Hospital
Associate Professor
Harvard Medical School
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Disclosure
 Dr. Naomi M. Simon has received grants
or research support from AstraZeneca,
Bristol-Myers Squibb, Cephalon, Forest,
GlaxoSmithKline, Janssen, Lilly, NARSAD,
NIMH, Pfizer, Sepracor, and UCB. She has
received honoraria for speaking from
Forest, Janssen, Lilly, Pfizer, Sepracor, and
UCB, and has been a consultant for
Paramount Biosciences and Solvay.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Anxiety and Insomnia in Women
 Epidemiology
 Presentation and course
 Menstrual fluctuations
 Menopause
 Pregnancy and postpartum
 Treatment implications
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender Differences in
Sleep Disturbances
 Women of all ages report greater insomnia





and inadequate sleep time
Objective findings less clear
Obstructive Sleep Apnea and Narcolepsy:
More common in men
Restless Legs Syndrome: Slight female
predominance clinically
Menstrual phase, pregnancy & menopause:
Roles sleep disruption
Anxiety and mood disorders as risk factor
Krishnan V, Collop N. Curr Opin Pulm Med. 2006;12(6):383-389.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Insomnia Is a Core Symptom
in Anxiety Disorders
 GAD: Worry and ruminations  insomnia
 PTSD: Nightmares and hyperarousal 


insomnia
Panic Disorder: Nocturnal panic and
anticipatory anxiety  insomnia
Rule out comorbid MDD and Bipolar Disorder
in setting significant insomnia
GAD= Generalized Anxiety Disorder; PTSD= Posttraumatic Stress Disorder;
MDD=major depressive disorder
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender Differences in Anxiety
Begin in Childhood
Cumulative Hazard of Anxiety Disorder by
Age at Onset and Gender (N=1221)
Cumulative Hazard
0.14
Female
Male
0.12
0.10
0.08
0.06
0.04
0.02
0
1
3
5
7
9
11
13
15
17
Age (Years)
Lewinsohn PM, et al. J Abnorm Psychol. 1998;107(1):109-117.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prevalence of Social Anxiety Disorder (SAD)
by Gender in a Large Epidemiologic Study
National Comorbidity Survey (NCS) Lifetime Prevalence
% Lifetime Prevalence
18
15.5%
16
14
13.3%
11.1%
12
10
8
6
4
2
0
Overall
Kessler RC, et al. Arch Gen Psychiatry. 1994;51(1):8-19.
Female
Male
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Epidemiology of Posttraumatic
Stress Disorder (PTSD)
 Prevalence of trauma exposure is higher in


men than in women (61% vs 51%)
Women exposed to trauma are twice as likely
to develop PTSD than men exposed to
trauma (20.4% vs 8.2%)
Lifetime prevalence of PTSD is twice as high
in women than in men (10.4% vs 5.0%)
Kessler RC, et al. Arch Gen Psychiatry. 1995;52(12):1048-1060.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Lifetime Prevalence Rates of Trauma
and Their Association With PTSD
Men
Women
%
Event
%
PTSD
%
Event
%
PTSD
Natural disaster
Criminal assault
Combat
Rape
18.9
11.1
6.4
0.7
3.7
1.8
38.8
65.0
15.2
6.9
–
9.2
21.3
–
45.9
Any trauma
60.7
8.1
51.2
20.4
Trauma
Kessler RC, et al. Arch Gen Psychiatry. 1995;52(12):1048-1060.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender and Epidemiology of
Panic Disorder (PD)
 Rates in NCS-R & worldwide: women 2x


men1,2
6-month prevalence highest in women ages
25-44 in Epidemiologic Catchment
Area (ECA) study3
Agoraphobia: women 2-4x men3
1. Kessler RC, et al. Arch Gen Psychiatry. 2006;63(4):415-424.
2. Weissman MM, et al. Arch Gen Psychiatry. 1997;54(4):305-309.
3. Weissman MM, Merikangas KR. J Clin Psychiatry. 1986;47(suppl):11-17.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender and the Presentation
of Panic Disorder
 No gender differences in panic attack




severity1
Women greater agoraphobic avoidance and
need for companion to leave home2
Higher rates of comorbid SAD and PTSD
Equivalent rates of comorbid depression1
Onset more closely associated with life
events in women3
Starcevic V, et al. Depress Anxiety. 1998;8(1):8-13.
Turgeon L, et al. J Anxiety Disord. 1998;12(6):539-553.
Barzega G, et al. Acta Psychiatr Scand. 2001;103(3):189-195.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender Differences in Panic Symptoms:
Data from the NCS (N=274)
 Greater in women
– Shortness of breath
– Feeling smothered
– Nausea
Sheikh JI, et al. Am J Psychiatry. 2002;159(1):55-58.
 Greater in men
– Abdominal pain
– Sweating
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Why Is Prevalence of Anxiety
Disorders Greater for Women?
Heritability
 Approximately
0.3-0.5 (moderate)
for generalized
anxiety disorder
(GAD), PD, and SAD
Environment
 Cultural expectations
 Societal roles–
artifact of reporting?
 Life events
Other
Biological Factors
 Modulation of serotonin
by estrogen
 Role of hormones and
cyclic fluctuations on
neurodevelopment?1
1. Joffe H, Cohen LS. Biol Psychiatry. 1998;44(9):798-811.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Is Anxiety Sensitivity a Heritable Risk
Factor for Panic Disorder in Women?
 Anxiety sensitivity (AS) is fear of physical
sensations and cognitive dyscontrol
 A twin study of 337 twin pairs found AS
heritable only in women (0.37-0.48 of
variance)
 Hypothesized that AS may in part explain
elevated rates of panic in women
Jang KL, et al. J Gend Specif Med. 1999;2(2):39-44.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Impact of Gender on Relapse of Anxiety Disorders:
8-Year Prospective Data — HARP Study (N=558)
0.7
*
Women
Men
Probability
0.6
*p=0.009
0.5
0.4
0.3
0.2
0.1
0
PD Without
Agoraphobia
PD With
Agoraphobia
HARP=Harvard/Brown Anxiety Research Program.
Yonkers KA, et al. Depress Anxiety. 2003;17(3):173-179.
Social Phobia
GAD
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Is There an Impact of Menstrual Cycle
Hormonal Fluctuation on Panic Disorder?
  anxiety and  anxiety response to inhaled CO2

in premenstrual phase vs midcycle in PD1
Inconsistent reports of premenstrual
exacerbation2
– Patients with PD who have a somatic focus (or
high anxiety sensitivity) may misinterpret physical
premenstrual symptoms3
Fishman SM, et al. J Psychiatr Res. 1994;28(2):165-170.
Basoglu C, et al. Compr Psychiatry. 2000;41(2):103-105.
Stein MB, et al. Am J Psychiatry. 1989;146(10):1299-1303.
Kaspi SP, et al. J Anxiety Disord. 1994;8:131-138.
Sigmon ST, et al. J Consult Clin Psychol. 2000;68(3):425-431.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Impact of Menstrual Cycle
on Anxiety
 PMS symptoms include anxiety, fatigue, and



changes in sleep
Screening study found PD in 14% with PMS
symptoms (n=426)1
Women with PMS and GAD report a greater
increase in anxiety premenstrually than those
with GAD alone2
Consider PMS/PMDD with cyclic changes in
anxiety
PMDD=premenstrual dysphoric disorder.
1. Yonkers KA, et al. Arch Women Ment Health. 2003;6(4):287-292.
2. McLeod DR, et al. Acta Psychiatr Scand. 1993;88(4):248-251.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Menstrual-Related Problems Linked to Insomnia,
Fatigue, Anxiety, and Depression (N=11,648)
% With Problem Last 12 months
35
Menstrual Problems
No Menstrual Problems
30
25
20
15
10
5
0
Insomnia
Excess Day
Sleepiness
Frequent Anxiety or
Depression
All p<0.05 in multivariate analyses.
Women aged 18-55: 19% reported menstrual problems = heavy bleeds, cramping, or PMS.
Strine TW, et al. J Womens Health (Larchmt). 2005;14(4):316-323.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender Differences in GAD Prevalence:
Is There an Impact of Perimenopause?
Lifetime Prevalence of GAD
12
Female
% Prevalence
10
Male
8
6
4
2
0
15-24
25-34
35-44
45
Age Group (Years)
Adapted from: Wittchen HU, et al. Arch Gen Psychiatry. 1994;51(5):355-364.
Halbreich U. Depress Anxiety. 2003;17(3):107-110.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Core Menopausal Symptoms
 Hot flashes: 60%-80%
 Insomnia disorder: 26% (vs. 13%)
 Major depression: 25%-33% (vs. 20%)
 Less attention to anxiety
Gold E, et al. Am J Public Health. 2006;96(7):1226-1235.
Ohayon MM, et al. Arch Intern Med. 2006;166(12):1262-1268.
Freeman EW, et al. Arch Gen Psychiatry. 2006;63(4):375-382.
Cohen LS, et al. Arch Gen Psychiatry. 2006;63(4):385-390.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prevalence of Panic Attacks in Postmenopausal
Women: An Ancillary Study to the Women’s
Health Initiative (N=3369)
% With Panic Attacks
25
Ages 50-59
Ages 60-69
Ages 70-79
20
*
15
10
5
0
Any
*p<0.05 in multivariate analyses.
Smoller JW, et al. Arch Intern Med. 2003;163(17):2041-2050.
Full-Blown
Limited-Symptom
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Correlates of Panic in Postmenopausal Women:
An Ancillary Study to the Women’s Health Initiative
(N=3369)
 Strongly linked to negative life events
 Associated with impaired social and role

functioning
Not linked to reported use of hormone
replacement therapy
Smoller JW, et al. Arch Intern Med. 2003;163(17):2041-2050.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sertraline vs Imipramine in Chronic Depression:
Responder Analysis by Menopausal Status
100
Imipramine
Sertraline
% Responding
80
*
60
57%
56%
57%
(n=203)
(n=25)
(n=49)
43%
40
20
(n=98)
0
Premenopausal
*p=0.007, imipramine vs sertraline.
Kornstein SG, et al. Am J Psychiatry. 2000;157(9):1445-1452.
Postmenopausal
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Menopause and Anxiety
Disorders
 Lack of data regarding impact of estrogen


loss or replacement therapy on anxiety
disorders
Perimenopause potentially associated with
increased risk of recurrence of previously
remitted anxiety disorder – data needed
Carefully follow patients with anxiety in
perimenopause
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Across Menopause
Transition
Subjective Sleep Quality
47.6
45.4
Percent
43.2
39.6
Early
peri
 No difference by
menopause status in
– Sleep latency
– Sleep efficiency
– Sleep staging
31.4
Pre
Objective Sleep Parameters
Late Post Surgical
peri (no HT) post
Adapted from Kravitz HM, et al. Menopause. 2003;10(1):19-28.
Shaver J, et al. Sleep. 1988;11(6):556-561.
Young T, et al. Sleep. 2003;26(6):667-672.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Potential Causes of Subjective Sleep
Disturbance During Peri/Postmenopause
 ↓ Sleep quality/insomnia
– Hot flashes
– Sleep apnea
– Chronic pain, poor health
– Anxiety
Ohayon MM, et al. Arch Intern Med. 2006;166(12):1262-1268.
Young T, et al. Sleep. 2003;26(6):667-672.
Hollander LE, et al. Obstet Gynecol. 2001;98(3):391-397.
Owens JF, Matthews KA. Maturitas. 1998;30(1):41-50.
Shaver J, et al. Sleep. 1988;11(6):556-561.
Freedman RR, Roehrs TA. Menopause. 2007;14(5):826-829.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Severity of Hot Flashes Associated
with Likelihood of Insomnia Disorder
50
p<0.001
43.8
40
30.3
30
%
23.3
20
10.5
10
0
None
Mild
Ohayon MM, et al. Arch Intern Med. 2006;166(12):1262-1268.
Moderate
Severe
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Hot Flashes and Sleep
Subjective Sleep Quality
Objective Sleep Parameters
 Consistent data
 Contradictory data
– Sleep quality worse in
women with hot
flashes
1. ~ or ↑ # awakenings
2. ~ or ↓ sleep efficiency
3. ~ or ↑ REM latency
Erlik Y, et al. JAMA. 245(17):1741-1744; Freedman RR, Roehrs TA. Fertil Steril. 2004;82(1):138-144;
Savard J, et al. J Pain Symptom Manage. 2004;27(6):513-522; Young T, et al. Sleep. 2003;26(6):667-672;
Hollander LE, et al. Obstet Gynecol. 2001;98(3):391-397; Mourits MJ, et al. Br J Cancer. 2002;86(10):1546-1550;
Owens JF, Matthews KA. Maturitas. 1998;30(1):41-50; Shaver J, et al. Sleep. 1988;11(6):556-561;
Ohayon MM, et al. Arch Intern Med. 2006;166(12):1262-1268.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Anxiety Severity Linked to Frequency
and Severity of Hot Flashes
Odds Ratio That Hot Flashes
Are Moderate-Severe
6
p<0.001
4.52
4
2.57
2
1
0
Low anxiety
Moderate anxiety
Zung Anxiety Scale, adjusted for age, race, depression, BMI, time
Freeman EW, et al. Menopause. 2005;12(3):258-266.
High anxiety
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Subjective Sleep Disturbance-Associated
Anxiety in Menopause (n=102)
 Medication free (psychotropic & HRT) women age
44-56 with reported insomnia
 Subjective report poor sleep quality on PSQI
correlated
– Hamilton Anxiety Score (p<0.002)
– Hot flashes 1st half night (p<0.01)
 Anxiety NOT linked to lab-based sleep efficiency
– Objective sleep disturbance found largely (53%) due
to sleep apnea & periodic leg movements
– Conclude need to rule out sleep disorders
HRT=Hormone Replacement Therapy; PSQI=Pittsburgh Sleep Quality Index
Freedman RR, Roehrs TA. Menopause. 2007;14(5):826-829.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Mechanisms of Objective Sleep
Disturbance During Peri/Postmenopause
 Hot flashes?
 Primary sleep disorders
– Sleep apnea
– Periodic limb movements
 Note: ↑ age as a confounding factor
Young T, et al. Am J Respir Crit Care Med. 2003;167(9):1181-1185.
Freedman RR, Roehrs TA. Menopause. 2007;14(5):826-829.
Ohayon MM, et al. Sleep. 2004;27(7):1255-1273.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep: NIH State-of-the-Science
Conference Statement
 Moderate evidence that menopause is the
cause of sleep disturbance in women
– Longitudinal cohort studies
– Observational studies
 Role of vasomotor symptoms is unclear
NIH State-of-the-Science Panel. Ann Intern Med. 2005;142(12 Pt 1):1003-1013.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Zolpidem for Insomnia in
Peri- and Postmenopause
 Zolpidem 10 mg vs placebo (N=141); 4 wks
– Improved PGI overall*
– Improved total sleep time*
– Decreased sleep latency (except weeks 2,3)
– No difference in LFS, GSD, RSQ
– Did not assess awakenings due to hot flushes
*p<0.05
PGI=Patient Global Impression; LFS=Lee Fatigue Scale; GSD=General Sleep Disturbance;
RSQ=Relationship Satisfaction Questionnaire
Dorsey CM, et al. Clin Ther. 2004;26(10):1578-1586.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Eszopiclone for Insomnia
in Perimenopause
 Eszopiclone 3 mg vs placebo (N=410); 4 wks
– Decreased sleep latency and improved quality*
– Improved next-day functioning*
– MADRS (8.36±7.15 vs 9.97±6.86)*
– SDS (mean change -0.84±2.29 vs -0.70±2.08)*
– Fewer awakenings due to hot flushes (0.29±0.55
vs 0.37±0.76)**
*p<0.05; **p=0.05.
MADR=Montgomery Asberg Depression Rating; SCS=Sheehan Disability Scale
Soares CN et al. Obstet Gyn. 200;108:1402-1410.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Sleep Disorders in Pregnancy
 Subjective sleep disturbance common; objective


measures minimal & mixed
Multiple potential biological and environmental causes
Increased rates, esp. first and third trimester:
–
–
–
–
Insomnia and reduced sleep efficiency
Restless Legs Syndrome (up to 25%)
Nocturnal Awakenings
Rarer Sleep Apnea
 Can contribute to or be part of anxiety and mood
disturbances
Sahota PK, et al. Curr Opin Pulm Med. 2003;9(6):477-483.
Soares CN, Murray BJ. Psychiatr Clin North Am. 2006;29(4):1095-1113.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Risks of Untreated Anxiety in
Pregnancy
 Risk due to sympathetic hyperarousal?
 Preterm labor
 Lower Apgar scores
 Direct effects of fetal-placental or

uteroplacental insufficiency
Potential increased risk of postpartum
worsening of anxiety in mother
Teixeira JM, et al. BMJ. 1999;318(7177):153-157.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
High Maternal Trait Anxiety Inventory
(>38): Impact on the Newborn (N=166)
 Lower weight babies




(34% vs 12% <2500 g, p<0.01)
 Serotonin and dopamine (urine)
Reduced vagal tone
Less time in quiet or active alert states
Poorer motor organization and autonomic
stability on Brazelton Neonatal Behavior
Assessment
Field T, et al. Depress Anxiety. 2003;17(3):140-151.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Prospective Study of Relapse of Panic During
Pregnancy: Impact of Medication Discontinuation
60
54%
% Relapse
50
40
25%
30
20
10
0
Medication Discontinuation
Attempt (n=24)
Maintained
(n=12)
OR=2.8 for relapse ( Clinical Global Impressions-Severity of Illness Scale [CGI-S] 2)
discontinuation in multivariate Cox model.
Cohen LS, et al. Presented at: 24th ADAA National Conference;
Mar 11-14, 2004; Miami, Fla.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Pregnancy: Course of
Panic Disorder
Retrospective Analysis With Variable
Medication Use and Discontinuation (N=49)
70
% of Patients
60
Baseline CGI 1-3 (n=25)
56% 58%
Baseline CGI 4-7 (n=24)
50
38%
40
36%
30
20
10
4%
4%
4%
0%
0
Same
CGI
Better
(CGI  2)
Worse
(CGI  2)
Note: 21/24 patients with CGI 4-7 on medications some portion of pregnancy.
14/25 patients with CGI 1-3 on medications.
Cohen LS, et al. J Clin Psychiatry. 1994;55(7):284-288.
Mixed
Course
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Postpartum: Course of
Panic Disorder
Retrospective Analysis (N=40)
70
65%
Discontinued
On medication by third trimester
% of Patients
60
50
40
35%
30
20
10
0
Same or Better CGI
Worse
( CGI 2)
Cohen LS, et al. J Clin Psychiatry. 1994;55(7):284-288.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Psychotropic Drug Use
in Pregnancy
 Drugs used when risk to mother and fetus




from disorder outweighs risks of
pharmacotherapy
Optimum risk/benefit decision for
psychiatrically ill pregnant women
Patients with similar illness histories make
different decisions
No decision is risk-free
See: www.womensmentalhealth.org
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Management of Insomnia in
Pregnancy
 Start with assessment and diagnosis
 Address sleep hygiene and pregnancy related
issues
– Adjust fluids night if nocturia
– Pillow support
 Behavioral therapy
 As with anxiety, consider severity insomnia,
examine current data re teratogenic risks, weigh
potential risks and benefits pharmacotherapy
Pien GW, Schwab RJ. Sleep. 2004;27(7):1405-1417.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Cognitive-Behavioral Therapy (CBT)
 Good option during pregnancy for both



anxiety and insomnia
12-week program is standard for anxiety
disorders
Focused on specific illnesses
May be used first-line or for patients with
intolerance or dislike of medication
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Potential Gender Differences in
Pharmacokinetics and Dose Effects?
 Minimal, mixed data on metabolism
of antidepressants
– Enzymes and plasma levels
 Role of estrogen on serotonin?
– Impact on SSRI efficacy in depression
 No clinical difference in treatment/dosing
to date
Yonkers KA, Brawman-Mintzer O. J Clin Psychiatry. 2002;63(7):610-615.
Schneider LS, et al. Am J Geriatr Psychiatry. 1997;5(2):97-106.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Lack of Gender Differences in
Response of GAD to SSRIs (N=370)
100
Sertraline
Placebo
% CGI Responder Rate
90
80
70
p<0.003
64%
p<0.001
62%
60
50
40%
40
34%
30
20
10
0
Men
Women
LOCF, endpoint 12 weeks.
Steiner M, et al. Hum Psychopharmacol. 2005;20:3-13.
This information concerns a use that has not been approved by the US FDA.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Gender and Anxiety Disorders:
Conclusions
  rates of anxiety disorders and reported insomnia
in women
 Insomnia core feature anxiety disorders
 Consider life cycle
– Pregnancy and postpartum
– Menstrual fluctuations
– Perimenopause
 Consider CBT strategies and counsel about
medications in pregnancy
 No clear significant gender differences
in pharmacotherapy
Presented at the 28th Annual Conference
Anxiety Disorders Association of America
Using your ResponseCard
 Questions will be displayed along with the





available answers
When the ten (10) second countdown clock
appears, press and release the button
that best represents your answer
A green light indicates your answer was received
Your last answer will be recorded
There is no need to press “GO” or “?”
Please leave the ResponseCard on the
table at the end of this session.
- Thank You.
Presented at the 28th Annual Conference
Anxiety Disorders Association of America