Behavioral versus Pharmacological Therapy for Adult Insomnia
Gary K. Zammit, Ph.D.Clinilabs
Columbia University College of Physicians and Surgeons
Conflict StatementI am deeply conflicted. I have been so for many years. It is an affliction that I blame on my parents, the Catholic church, and several institutions of higher learning. Most of my conflicts were personal, until a few years ago when I had to start revealing my conflicts to the public whenever I gave a lecture. Apparently, this is a rule that only applies to me, since I’ve never seen anyone else reveal all of their potential conflicts. Having been exposed to clinical training and psychoanalytic psychotherapy for many years in my youth, my interpretation of conflict may be more expansive than others, who seem to think that conflicts only relate to one’s finances. I know better; conflicts certainly run deeper than that and often are seated in the unconscious mind. I would be happy to speak with you about all of my conflicts, preferably over a martini. However, if you primarily are interested in learning about my financial conflicts, I can say with brevity and unabashed honesty that I have none. I believe that I should be compensated for an honest day’s work, I seek to obtain such compensation whenever possible, and I encourage anyone who cares to listen to do the same. I see no conflict there, and I will be happy to debate anyone on this topic so long as they do not have other conflicts like I do because I find that those debates require lengthy discussion for which I simply am not equipped and no longer have the time.
Conflicts of Interest Grants/Research Support: Abbott, Actelion, Ancile, Apnex, Arena, Aventis,
Cephalon Inc., CHDI, Elan, Epix, Evotec, Forest, Galderma, Glaxo Smith Kline, H. Lundbeck A/S, King, Merck and Co., Johnson & Johnson, National Institute of Health (NIH), Neurim, Neurocrine Biosciences, Neurogen, Organon, Orphan Medical, Pfizer, Respironics, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plough, Sepracor, Shire, Somaxon, Takeda Pharmaceuticals North America, Targacept, Thymon, Transcept, UCB Pharma, Predix, Vanda, Wyeth-Ayerst Research
Consultant: Actelion, Alexza, Arena, Aventis, Biovail, Boehringer-Ingelheim, Cephalon, Elan, Eli Lilly, Evotec, Forest, Glaxo Smith Kline, Jazz, King Pharmaceuticals, Ligand, McNeil, Merck, Neurocrine Biosciences, Organon, Pfizer, Renovis, Sanofi-Aventis, Select Comfort, Sepracor, Shire, Somnus, Takeda Pharmaceuticals, Vela, Wyeth
Honoraria: Neurocrine Biosciences, King Pharmaceuticals, McNeil, Sanofi-Aventis, Sanofi-Synthelabo, Sepracor, Takeda Pharmaceuticals, Vela Pharmaceuticals, Wyeth-Ayerst Research
Ownership, Directorship: Clinilabs, Inc., Clinilabs IPA, Inc., Clinilabs Physician Services, PC.
Industry Stocks Held: None outside of mutual funds
Presentation and Learning Objectives
The objectives of this presentation are to:• Define primary and co-morbid insomnia
• Identify drug treatments for insomnia, and present data regarding their efficacy and safety
• Identify behavioral treatments for insomnia, and present data regarding their efficacy and safety
• Address the merits of behavioral and drug treatments of insomnia, comparing and contrasting the utility of both in clinical practice
• Attendees will gain an understanding of behavioral and drug treatments for insomnia, and their possible use in clinical practice.
The Definition of Insomnia
Difficulty Initiating Sleep
Difficulty Maintaining Sleep
Non-restorative1 or Poor Quality Sleep2
Associated with Clinically Significant1 or Marked2 Distress or Impairment
At Least 1 Month in Duration1,2 (3x/Week2)
Preoccupation with Sleeplessness and Excessive Concern over its Consequences2
1 APA. Diagnostic and Statistical Manual of Mental Disorders - 4th Edition, Text Revision. 2000.2 WHO. International Statistical Classification of Diseases and Related Health Problems, 10 th Revision, 2006
One or More of the Following Symptoms Must be Present
Prevalence of InsomniaThe American Insomnia Survey
Methods: Epidemiological survey of managed health care plan subscribers (n = 10,094), assessed for insomnia with the Brief Insomnia Questionnaire, a clinically validated scale generating diagnoses according to DSM-IV-TR; International, ICD-10, and RDC criteria
Results: Insomnia prevalence estimates varied widely, from 22.1% for DSM-IV-TR to 3.9% for ICD-10 criteria• Although ICD insomnia was associated with significantly worse
perceived health than DSM or RDC/ICSD insomnia, DSM-only cases also had significant decrements in perceived health.
Conclusions: Insomnia is highly prevalent and associated with substantial decrements in perceived health.
Roth, T., Coulouvrat, C., Hajak, G., et. al., 2011, Biological Psychiatry, 69, 592 – 602.
Landmark Report on InsomniaState-of-the-Science
Estimates 10% of adults with insomnia associated with impairment National Institutes of Health State-of-the-Science Conference on
the Manifestations and Management of Chronic Insomnia in Adults (2005) 1
• Underscores need for appropriate diagnosis and treatment of insomnia
• Emphasizes need for further education and research on insomnia as a condition2
Chronic insomnia is a major public health problem affecting millions of individuals, along with their families and communities
1. NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults. J Clin Sleep Med. 2005; 412 - 421
2. Colten HR et al. Institute of Medicine of the National Academies. Washington, DC. National Academies Press. 2006.
Difficulty falling asleep
~50%
Sleep maintenance problems†
~70%
Poor sleep quality
~40%
*n=570†Interrupted sleep and early morning awakening.
Leger D et al. Curr Med Res Opin. 2005;21:1785-1792.
Symptoms of individuals who reported sleep disturbances
during last 12 months
Sleep Maintenance Insomnia Most Common
US results (n=2,061):27.1% insomnia prevalence • from an international
telephone survey (N=5,132)
Of US patients withsleep disturbances:*
• 42% have sleep problems[nearly] every night
• Mean number of symptoms is 1.9
• 24% report all 3 symptoms
Sleep Maintenance Insomnia:A Clinically Relevant Distinction
METHODS: Cross-sectional telephone study was performed in the non-institutionalized
general population of France, the United Kingdom, Germany, Italy and Spain.• Representative sample of 22,740 non-institutionalized individuals age ≥15• DRS defined as a complaint of difficulty in resuming or inability to resume sleep occurring at least three
nights per week and lasting for at least one month.
RESULTS: A total of 16.1% [95% CI: 15.6-16.6] of the sample had DRS
• Prevalence higher in women and increased with age, mean duration 40 months• DRS individuals slept on average 30 min less than other subjects with insomnia symptoms and 60 min less
than the rest of the sample• Psychiatric conditions more common. Daytime impairment was observed in 52.2% of DRS individuals
compared to 32.8% in individuals with classical insomnia symptoms (p < 0.0001).
CONCLUSIONS:• DRS affect a large segment of the population• DRS is a good indicator of an ongoing sleep or mental disorder• DRS has a stronger impact on daytime functioning than classical insomnia symptoms (OR: 4.7).
Ohayon, M. 2009. Journal of Psychiatry Research, 43, 934 – 940.
Symptoms of Insomnia are Persistent: Chronicity Documented by Empirical Research
Insomnia is a chronic condition1
Insomnia is a chronic condition in the elderly2
Epidemiological study included 870 subjects with insomnia• 69% continued to have insomnia at 12-month follow-up3
64-month longitudinal data in 28 patients well-characterized with insomnia4
• Initial 100% • 40 months 70.4%• 64 months 88.2%
Seven-year follow-up study of young adults with insomnia indicates that insomnia persists in 8% - 10%, with recurrent, brief episodes of insomnia in 13% - 19%5,6
1.Katz, McHorney, Arch. Internal Medicine, 1998; 2. Ganguli, M, Reynolds, CF, Gilby, JE. J. Am. Geritric Society, 1996; 3. Morphy, Dunn, Lewis, et. al., Sleep, 2007; 4. Mendelson, WB. Sleep, 1995; 5. Angst, J, Vollrath, M, Koch, R, et. al. Eur. Arch. Psychiatr. Clin. Neurosci., 1989; 6. Vollrath, M, Wicki, W., Angst, J. Eur. Arch. Psychiatr. Clin. Neurosci, 1989
INSOMNIA DURING 2-YEAR FOLLOW-UPKatz and McHorney, Arch Intern Med, 1998
0
10
20
30
40
50
60
70
80
No insomnian = 801
Mild insomnian = 557
Severe insomnian = 264
Baseline statusNo insomnia Mild insomnia Severe insomniaFollow-up status
% o
f su b
j ec t
s
NIH State-of-the-Science Conference Statement Recognizes Chronic Insomnia:
The NIH report indicates that…
“the panel is concerned about the mismatch between the potential lifelong nature of this illness and the longest clinical trials, which have lasted 1 year or less…”
An Important Paradigm Shift: Recognition of chronic insomnia may influence research and clinical practice, with implications for long-
term treatment
NIH. National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005, Sleep, 2005 Sep 1;28(9):1049-57.
NIH State-of-the-Science Conference and Co-Morbid Insomnia
As much as 85% of all insomnia may be co-morbid with other conditions
“Co-morbid insomnia” is an appropriate term• Mechanistic and causal pathways not known
• The term secondary insomnia may promote undertreatment
NIH. National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005, Sleep, 2005 Sep 1;28(9):1049-57.
Insomnia: Often Comorbid Cardiovascular diseases
• Ischemic heart disease• Nocturnal angina
Respiratory diseases• Chronic obstructive pulmonary disease • Bronchial asthma
Gastrointestinal diseases• Peptic ulcer disease• Gastroesophageal reflux
Neurological diseases• Parkinson’s/Alzheimer’s
Rheumatic disorders• Fibromyalgia• Osteoarthritis
Psychiatric disorders Dyspnea (from any cause)
Endocrine syndromes• Diabetes• Menopause• Hyperthyroidism
Pain (from any cause) Associated sleep disorders
• Sleep apnea• Restless legs syndrome• Periodic limb movement disorder
Miscellaneous conditions• Dermatologic• Chronic fatigue syndrome• HIV/AIDS• Lyme disease• Systemic cancer• Pregnancy• Medical treatment induced
Thase ME. Gen Hosp Psychiatry. 2005;27:100-112.
QUALITY OF LIFE IN INSOMNIAMETHODS
INSOMNIA GROUP Insomnia at least 3 times per
week for at least 1 month Typical sleep latency greater than
or equal to 30 minutes 3 or more awakenings per night,
with difficulty returning to sleep Total sleep time less than 6.5
hours per night No history of serious medical,
psychiatric, or sleep disorder
CONTROL GROUP No history of insomnia Regular periods of nighttime sleep No history of serious medical,
psychiatric, or sleep disorder
362 men and women,18 - 75 years of age, were prospectively studied 261 (72%) met criteria for the insomnia group101 (28%) met criteria for the control group
Zammit GK et al. Sleep. 1999;22(suppl):S379-S385.
Burden of Insomnia on Quality of Life
Significant differences were observed between insomnia and control subjects on all scales of the SF-36, all significant at the P<.0001 level
Zammit GK et al. Sleep. 1999;22(suppl):S379-S385.
95
75
55
35
P<.0001
N=362
Control
Insomnia
Body Pain General Health
Mental Health
Role Emotional
Role Physical
Social Functioning
Vitality Physical Functioning
SF
-36
Sca
le S
core
Insomnia Impacts Quality of Life
Health and Insomnia
Short sleep duration is associated with myriad health risks• Obesity
• Diabetes
• Hypertension
• Hypercholesterolemia
• Depression
Insomnia is associated with risk of psychiatric illness• Depression
• Anxiety
Gangwisch, J., et. al., 2005, Sleep, 28, 1289 – 1296; Gangwisch, J. et. al., 2007, Seep, 30, 1667 – 1673; Gangwisch, J. E., et. al., 2006, Hypertension, 47, 833 – 839; Gangwisch, J. E., 2010, Sleep, 33, 956 – 961; Gangwisch, J. E., 2010, 33, 97 – 106; Breslau, N., et. al., 1996, Arch. Gen. Psychiatry.; Buysse, D., et. al., 2008, Sleep.
The Debate: Treatment Considerations Insomnia is a common condition
• Treatment should be widely available
Sleep maintenance insomnia is the most common form of insomnia• Treatment should enable patients to stay asleep or fall asleep easily after an
awakening
Insomnia is a chronic condition• Should have sustained efficacy or available for long-term use
Insomnia often is co-morbid• Treatment should be able to be used in context of other illness
Insomnia is associated with impairment and health risk• Treatment should be safe and reduce impairment and improve health
outcomes
Treatments for Insomnia
Pharmacologic treatments• Hypnotics
Behavioral treatments• Sleep hygiene
• Stimulus control therapy
• Sleep restriction therapy
• Cognitive-behavioral therapy
• Relaxation therapy
• Paradoxical intent
Hypnotics are Widely Available
Primary care physicians increasingly aware of sleep disorders, including insomnia
Primary care physicians and “physician extenders” (e.g., physician assistants) can prescribe hypnotics
Common treatment indicated for insomnia is now generic (zolpidem)• Affordability
Greater than 56 million prescriptions for insomnia were issued in 2008 indicating wide availability of hypnotics1
1IMS Health, 2009, reference in USA Today 03/01/2009
Eszopiclone Efficacy and Safety
Randomized, double-blind, placebo-controlled, multicenter, outpatient study in adults with chronic primary insomnia
Entry criteria• Primary insomnia, self-reported average sleep duration 6.5
hrs/night and sleep onset latency > 30 min Treatments and duration
• Six month double-blind Tx period: Esz 3 mg vs placebo nightly• Six-month open-label extension period: Esz 3 mg nightly
Method• Subjects required to use 3 doses per week (7‑day period), or
15 doses per month (30‑day period), to continue in study
Krystal et al. Sleep. 2003:26;793-799
Self-Reported Sleep Onset Latency (SOL)
**P < 0.01; P-values represent within-group pairwise comparisons at each point for all groups.
**************
ESZ LOCF Placebo LOCF
0
10
20
30
40
50
60
70
0 1 2 3 4 5 6
ESZ Observed Placebo ObservedESZ Completers Placebo Completers
Me
dia
n m
inu
tes
Month
Krystal et al. Sleep. 2003:26;793-799
Self-Reported Wake Time After Sleep Onset (sWASO)
*P < 0.05; +P = 0.07 for Observed; P-values represent within group pairwise comparisons at each point for all groups.
Month
0
10
20
30
40
50
60
0 1 2 3 4 5 6
ESZ Observed Placebo Observed
Me
dia
n m
inu
tes
*******
ESZ LOCF Placebo LOCFESZ Completers Placebo Completers
Krystal et al. Sleep. 2003:26;793-799
Low-Dose Doxepin Reduces WASO
Objective: To evaluate the efficacy and safety of doxepin 1 mg and 3 mg in elderly subjects with chronic primary insomnia
Methods: • Randomized, double-blind, parallel-group, placebo-controlled trial• Subjects meeting DSM-IV-TR criteria for primary insomnia were
randomized to 12 weeks of nightly treatment with doxepin (DXP) 1 mg (n = 77) or 3 mg (n = 82), or placebo (PBO; n = 81)
• Efficacy was assessed using polysomnography (PSG), patient reports, and clinician ratings
• Objective efficacy data were reported for Nights (N) 1, 29, and 85• Self-report efficacy data during Weeks 1, 4, and 12, Clinical Global
Impression (CGI) scale, and Patient Global Impression (PGI) were obtained
• Safety assessments were conducted throughout the study.
Krystal, A., et. al., 2010, Sleep, 33 (11), 1553 - 1561
Low-Dose Doxepin Reduces WASO
70
80
90
100
110
120
130
Baseline Night 1 Night 85
Placebo Doxepin 1 mg Doxepin 3 mg
**
** **
*P< 0.05,** p< 0.0001
p < .001 for zolpidem-pill vs. placebo-pill
Efficacy of Non-Nightly Zolpidem over 8 Weeks: Self Reported Total Sleep Time
300
320
340
360
380
400
420
Weeks 1-2 Weeks 3-4 Weeks 5-6 Weeks 7-8
Placebo pill n=71 Placebo no pill n=71
Zolpidem 10 mg pill n=63 Zolpidem no pill n=63
min
utes
* * * *
*Walsh et al., Sleep, 2000
Use of Hypnotics in Co-Morbid Insomnia
Depression• Improvements in SL, WASO, and TST after treatment with
eszopiclone and fluoxetine1
Generalized anxiety disorder• Total sleep time improved after treatment with zolpidem and
escitalopram2
Chronic pain• Eszopiclone significantly improved all patient-reported sleep
measures (WASO, SL, and TST), sleep quality, depth of sleep, and daytime function (P < .05 vs placebo); 48% of eszopiclone-treated patients had no clinically meaningful insomnia as assessed by ISI score (versus 30% of placebo-treated patients (P = .03)3
1Krystal, A., et. al., 2007, J. Clinical Sleep Medicine,3, 48 – 55; 2Fava, M., et. al., 2009, J. Clinical Psychopharmacol., 29, 222 – 230; 3Roth, T., et. al., 2007, Primary Care Companion J. Clinical Psychiatry, 11, 292 - 301
Most Common AEs in 5-Week Placebo-Controlled Study of Ramelteon in Adults with Insomnia
AE Placebo
n = 131
Ramelteon 8 mg
N = 139
Ramelteon 16 mg
n = 135
Any 48.1% 51.1% 54.8%
Headache NOS 18.3% 19.4% 17.8%
Somnolence 1.5% 7.9% 7.4%
Fatigue 2.3% 9.4% 4.4%
Nausea 2.3% 4.3% 4.4%
Nasopharyngitis 3.1% 2.9% 3.7%
Diarrhea NOS 1.5% 1.4% 3.7%
URI NOS 3.1% 4.3% 0.7%
Dizziness 3.8% 3.6% 1.5%
Nasal Congestion 0.8% 1.4% 3.0%
* All reported AEs ≥ 3%Zammit et al. 2007. Journal of Clinical Sleep Medicine, 3, 495 - 504
Low Frequency of Reported Adverse Reactions to Sedative Hypnotics in Hospital Setting
Drug ClassTotal Doses Dispensed
Reported Adverse Events Frequency (%)
Chloral Hydrate 2,768 0 0
Pentobarbital 546 0 0
Temazepam 79,016 3 0.004
Triazolam 9,656 2 0.02
•Data derived from 3,000 cases per year of adverse drug reactions•Presented to Drug Outcomes Management Committee for review•AEs entered into database over 3 year period
Mendelson, W., et. al. (1996). Sleep, 19, 702 – 706;
Low Rate of AEs Reported in Outpatient Clinical Practice
Uncontrolled surveillance study• Office-based physicians• Examined 16,944 patients with insomnia who were given zolpidem
during a four-week period Total of 268 AEs (1/113, 2/53, >2/16)
• Overall rate of 0.006% There were 118 discontinuations due to AEs
• Nausea (36)• Dizziness (35)• Malaise (23)• Nightmares (20)• Agitation (19)• Headache (18)
Hajak, G. & Bandelow, B. (1998). Int. Clin. Psychopharmacol., 13, 157 - 167
Residual Effects of Hypnotics
Residual effects refer to continued sedation or impairment in memory and psychomotor functioning following morning awakening
Assessed using self-report measures and objective test data• Digit symbol substitution test• Symbol copying test• Immediate and delayed recall tests• Driving performance
Residual effects of BZRAs may be related to dose, half-life, and time of dose
Recently-approved therapeutics not associated with significant residual effects
Blin, et. al., 2006. J. Clin. Psychopharmacol., 26, 284 – 289; Vermeeren, A., 2004, CNS Drugs, 18, 297 - 328
Potential Residual Memory Effects of Benzodiazepine Hypnotics
0
2
4
6
8
10
12
14
16
Mean Items ImmediateRecall
Mean Digits ImmediateRecall
Mean Items MorningRecall
Mean Digits MorningRecall
Placebo
Flurazepam
Lorazepam
Triazolam
Roth, et. al., (1980). Psychopharmacology, 70, 231 - 237
Next-Day Psychomotor FunctioningS
co
re (
med
ian
)
Zammit et al. Curr. Med. Res. Op., 2004, 20, 1979 - 1991
Mean +/- 1 SD for age group 35-44 norm – Wechsler adult intelligent scale
Morning DSST Scores^
^Mean of 3 time points (days 1, 15, & 29)
0
10
20
30
40
50
60
70
Placebo ESZ 3 mgBaselineBaseline
Imp
rov
em
en
t
Driving Studies
Standardized highway driving tests 100 km (61 miles) over highway circuit at constant speed Primary outcome: standard deviation from lateral position (SDLP) 11 studies using this methodology have provided data
• Zaleplon 10 mg, 20 mg: No significant effects > 2hours post-administration
• Temazepam 10 mg, 20 mg, 30 mg: Low incidence of driving impairment
• Zolpidem 10 mg: Moderate to severe impairing effects 5 – 7 hours post-administration
• Flurazepam 30 mg: Severe impairment, greater than equivalent BAC of 1.0 g/L
• Triazolam 0.5 mg: Marked residual effects, dose-dependent; with effects in first hour after rising following 0.25 mg and 0.125 mg
Vermeeren, A., 2004, CNS Drugs, 18, 297 - 328
Benzodiazepine Use and Risk of Falls1 and Fractures2 in Older Women
0
1
2
Frequent falls Non-spine fracture Hip fracture
Outcome
Short-acting
Long-acting
n=8,127
1Ensrud KE et al. J Am Geriatr Soc 2002;50:1629–37; 2Ensrud KE et al. Arch Intern Med 2003;163:949–57.
Rel
ativ
e R
isk
Postural Instability and Hypnotic UseSensory Organization Test Composite Score
SO
T S
core
Cha
nge
from
Bas
elin
e
Zammit, G. K. 2008. BMC Geriatrics.
Abuse and Dependence Liability
Hypnotic abuse and dependence are a concern of practitioners and patients
Evidence of hypnotic abuse or dependence among people with insomnia is minimal
Most indicators of abuse or dependence not evident in people with insomnia who use hypnotics• Withdrawal• Non-therapeutic use• Tolerance• Dose escalation
Discontinuation Effects of Hypnotics
Rebound insomnia is most frequently reported discontinuation effect• Typically 1 – 2 nights• May occur following even short-term use1
• Does not increase in severity with longer durations of use
• More likely to occur with high doses Rebound insomnia must be differentiated from
recrudescence or withdrawal2
1. Roehrs, T., et. al., 1992, Psychopharmacology, 107, 480 – 484; 2. Walsh, J., et. al., Principles and Practice of Sleep Medicine, 4th Edition
Limited Evidence of Withdrawal Effects with Commonly-Prescribed Hypnotics
Period 1 Period 2 Period 3 Period 4
TST
Baseline 319.5 320.3 321.2 323.5
1st Night Off 307.0 315.4 334.6 337.5
SL
Baseline 76.1 75.7 75.9 72.3
1st Night Off *90.1 89.4 76.2 75.5
NAW
Baseline 2.35 2.34 2.38 2.41
1st Night Off 2.62 2.25 2.24 2.09
Walsh, J., et. al., 2000, Sleep, 23, 1087 - 1096 *P < 0.04
Relative Abuse Liability of 19 HypnoticsPentobarbital
MethaqualoneDiazepam
FlunitrazepamLorazepam
GHBTemazepam
ZaleplonEszopiclone
TriazolamZopiclone
FlurazepamZolpidem
EstazolamOxazepam
DiphenhydramineQuazepamTrazodoneRamelteon
0 20 40 60 80 100
Likelihood of Abuse
Toxicity
Score
Griffiths R, Johnson M. 2005, J Clin Psychiatry, 66 (suppl 9): 31 - 41
Sedative-Hypnotic Drug Products Class Safety Labeling
December 2006, FDA requested that the whole class of hypnotic drugs revise product labeling to include warnings about the following potential adverse events:
Anaphylaxis (severe allergic reaction) Angioedema (severe facial swelling) Complex sleep-related behaviors Letters to health care providers. Patient Medication Guides to inform consumers
Treatment Considerations
Variable PharmacotherapyBehavioral Therapy
Widely Available Yes
WASO or sWASO Yes
Sustained Efficacy or Available for Long Term Use
Yes
Use in Co-Morbid Insomnia Yes
Reduce Impairment or Health Risk
No
Safe Concerns
Behavioral Treatment for Insomnia is Not Widely Available
Availability of behavioral treatment is severely limited• Lack of trained clinicians• Poor geographic distribution of knowledgeable
providers• Inaccessibility to treatments and clinicians
Behavioral treatment paid at lower rates than physician visits for medical care
Multiple visits required for treatment that meets current standard of care
Ritterband, L. M., et. al., 2009, Archives of General Psychiatry, 66, 692 - 698
Meta-Analysis of the Efficacy of Behavioral Treatments for Insomnia
Objective: Meta-analysis of behavioral treatments for insomnia Methods: A systematic review was conducted on 37 treatment
studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively
Criteria for inclusion of a study were as follows• Main sleep diagnosis was insomnia (primary or comorbid)
• At least 1 treatment condition was psychological or behavioral in content
• The study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects
• The study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality
Morin, C., et. al., Sleep, 2006, 29, 1398 1414
Meta-Analysis of the Efficacy of Behavioral Treatments for Insomnia
Seventeen studies examined CBT in primary insomnia, five of which were randomized, controlled clinical trials
Overall, studies showed that CBT had greater improvement on sleep diary and PSG variables than control conditions
Twenty-six studies provided follow-up data, indicating the durability of behavioral treatment over short, intermediate, and long (>12 months) periods
Benefits observed when specialists or non-specialists (e.g., primary care physicians, nurse practitioners) administered treatment
Morin, C., et. al., Sleep, 2006, 29, 1398 1414
Behavioral Therapy Reduces WASO
Objective To test the efficacy of a hybrid cognitive behavioral therapy (CBT) compared with both a first-generation behavioral treatment and a placebo therapy for treating primary sleep-maintenance insomnia.
Design: Randomized, double-blind, placebo-controlled clinical trial Patients Seventy-five adults (n=35 women; mean age, 55.3 years) with
chronic primary sleep-maintenance insomnia (mean duration of symptoms, 13.6 years)
Interventions Patients were randomly assigned to receive outpatient CBT (sleep education, stimulus control, and time-in-bed restrictions; n=25), progressive muscle relaxation training (RT; n=25), or a quasi-desensitization (placebo) treatment (n=25) for six weeks, with follow-up conducted at 6 months.
Main Outcome Measures: Polysomnography and sleep log measures of total sleep time, middle and terminal wake time after sleep onset (WASO), and sleep efficiency
Edinger, J., et. al., 2006, JAMA, 285, 1856 - 1864
Behavioral Therapy Reduces WASO
Edinger, J., et. al., 2006, JAMA, 285, 1856 - 1864
MeasureBaseline
MeanCBT RT Placebo P Value Post-Hoc Test
TST Log 336.8m 360.0m 362.0m 361.0m 0.99
TST PSG 352.1m 372.4m 337.9m 334.0m 0.02 CBT>P
WASO Log 56.2m 28.1m 44.4m 47.1m 0.004 CBT<RT&P
WASO PSG 50.8m 30.1m 50.6m 66.4m 0.02 CBT<P
WAST Log 47.7m 21.1m 36.2m 47.0m 0.02 CBT<P
WAST PSG 14.1m 4.2m 10.2m 12.4m 0.02 CBT<P
SE Log 72.0% 84.3% 78.1% 76.2% 0.002 CBT>RT&P
SE PSG 77.8% 85.5% 78.1% 75.7% 0.002 CBT>RT&P
Behavioral Therapy & Co-Morbid Insomnia Chronic pain:
• SOL, WASO, SE improved following CBT versus control1o SOL reduced from 55 minutes to 28 minuteso SE increased from 72% to 85%
Medical Illness• In a study of 51 older adults, WASO and SE improved following
CBT or RT versus control2
• In a study of 49 older adults with insomnia associated with medical and psychiatric conditions,3 a combined intervention of stimulus control, relaxation, and education reduced WASO 25 min and increased SE 11% at post treatment
o Fifty-seven percent (57%) of treated patients achieved clinically significant improvements on SE relative to 19% of control patients
1Currie, S.R., et. al., 2000, Journal of Consulting and Clinical Psychology, 68, 407 – 416; 2Rybarczyk, B., et. al., 2002, Psychological Aging, 17, 288 – 298; 3Lichstein, K.L., et. al., 2000, Psychol Aging, 15, 232 - 240
Brief Behavioral Treatment for Insomnia
Objective: To assess the efficacy of individualized behavioral treatment for insomnia, delivered in two sessions and two telephone calls
Primary outcome: Categorical status at four weeks following the initiation of treatment
Sample: Seventy-nine elderly adults, 54 female, recruited from the community and one primary care clinic
Method: Participants were randomly assigned to receive BBTI or IC (information control) over a four-week period. • All treatments were administered by a nurse clinician
Buysse, D., et. al., Archives of Internal Medicine, 2011, e-pub January 24, 2011
Brief Behavioral Treatment for InsomniaOutcome After Four Weeks of Treatment
0
10
20
30
40
50
60
70
Remission Response PartialRemission
Non-Response
BBTI (n = 39) IC (n = 40)
0
10
20
30
40
50
60
No Longer Meet DSM-IV Criteria
BBTI (n = 39) IC (n = 39)
(P<.001)
Buysse, D., et. al., Archives of Internal Medicine, 2011, e-pub January 24, 2011
Internet Expansion of Access to Care
OBJECTIVE: Evaluate structured behavioral Internet intervention for adults with insomnia.
DESIGN, SETTING, AND PARTICIPANTS• Forty-five adults randomly assigned to an Internet intervention (n = 22) or wait-list
control group (n = 23). INTERVENTION: The Internet intervention based on well-established face-to-face
cognitive behavioral therapy incorporating the primary components of sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and relapse prevention
MAIN OUTCOME MEASURES: The Insomnia Severity Index and daily sleep diary data were used to determine changes in insomnia severity and the main sleep variables, including wake after sleep onset and sleep efficiency
RESULTS• Insomnia Severity Index significantly improved from 15.73 for the Internet group
but did not change for the control group (P < .001)• The Internet group maintained gains at the 6-month follow-up• Internet participants achieved significant decreases in wake after sleep onset
(55%) and increases in sleep efficiency (16%) compared with the nonsignificant control group changes of wake after sleep onset 8% and sleep efficiency 3%
Ritterband, L.M., et. al. 2009. Arch. Gen. Psychiatry, 66, 692
Comparison of CBT, Zopiclone, and Placebo Objective: To examine short- and long-term clinical efficacy of CBT, zopiclone
7.5 mg, and placebo in older adults experiencing chronic primary insomnia. Design: Randomized double-blinded, placebo controlled trial of 46 adults
(mean age, 60.8 y; 22 women) with chronic primary insomnia Intervention: CBT (sleep hygiene, sleep restriction, stimulus control, cognitive
therapy, and relaxation; n=18), sleep medication (7.5-mg zopiclone each night; n=16), or placebo (n=12)• All treatment duration was 6 weeks• Follow-up at 6 months.
Main Outcome Measures: Ambulatory PSG and sleep diaries Results:
• CBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures.
• At 6 weeks, CBT improved sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group
• At 6 months patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone
Silversten, B. et. al. 2006. JAMA, 295, 2851
Combined use of B and P Objectives To evaluate the added value of medication over CBT alone for acute
treatment of insomnia and the effects of maintenance therapies Design: Randomized controlled trial involving 2-stage therapy for 160 adults with
persistent insomnia Interventions CBTalone or CBT plus 10mg/d zolpidem for an initial 6-week therapy,
followed by extended 6-month therapy.• CBT received monthly maintenance CBT for 6 months or received no additional treatment• Combined continued with CBT plus intermittent use of zolpidem or CBT only
Main Outcome Measures SoL, TST, SE derived from diaries; treatment response and remission rates derived from the Insomnia Severity Index
Results CBT used singly or in combination with zolpidem produced significant improvements in SoL, SE during initial therapy (all P.001)
Larger increase of sleep time was obtained with the combined approach (P=.04) Combined therapy produced a higher remission rate compared with CBT alone
during the 6-month extended therapy phase and the 6-month follow-up period (56% vs 43%, P=.05)
Best long-term outcome seen in combined therapy initially, followed by CBT alone, as evidenced by higher remission rates at the 6-month follow-up compared with patients who continued to take zolpidem during extended therapy (68% vs 42%, p<.04)
Zolpidem 10 Mg PRN Alone and with Stimulus Control Therapy
Overview Prospective, observational study in 550 primary care settings in
GermanySample 2,690 patients with chronic insomnia (mean age 59 years) Female 66% Average duration of insomnia = 5.2 years Prior use of patients who received prior pharmacotherapy = 49.7%Method Zolpidem 10 mg HS alone prescribed for “as needed” use, up to a
maximum of 5 tablets per week for three weeks After three weeks of treatment, use of standard stimulus control
therapy was optional on non-drug nights. Hajak, Bandelow, Zulley, et. al., Annals of Clinical Psychiatry, 14, 2002
Average Zolpidem Use During Treatment Periods
3.7
2.6
0
0.5
1
1.5
2
2.5
3
3.5
4
Zolpidem 10 mg PRN After 3 Weeks (Opt. SC)
Hajak, Bandelow, Zulley, et. al., Annals of Clinical Psychiatry, 14, 2002
P < 0.00001
3.7 Tabs
2.6 Tabs
Num
ber
of T
able
ts
Treatment Considerations
Variable PharmacotherapyBehavioral Therapy
Widely Available Yes Not Yet
WASO or sWASO Yes Yes
Sustained Efficacy or Available for Long Term Use
Yes Yes
Use in Co-Morbid Insomnia Yes Yes
Reduce Impairment or Health Risk
No No
Safety Concerns + -
Relative Merits and Considerations
Drug treatments are widely available, efficacious, and impact key sleep outcomes (WASO), but safety concerns persist
Behavioral treatments are not as widely available but are efficacious, impact key sleep outcomes, and are associated with fewer concerns than drug treatments
Neither drug or behavioral treatments have been shown to improve daytime functioning or health outcomes
Practice guidelines emphasize the value of clinician judgment in treatment planning
“B vs. P” State of the Science
Studies are needed to evaluate the effectiveness insomnia treatments in improving measures of clinical significance, such as daytime function, quality of life, health outcomes
Further research is needed to comparing the effectiveness of single versus combined drug, device, psychological, or behavioral therapies for insomnia.
Further research is to identify patient groups where combination or single therapy is most appropriate.
Studies are needed that compare treatments for insomnia with regard to their short and long-term effectiveness, risks/benefits, costs, and patient satisfaction.