Behavioral versus Pharmacological Therapy for Adult Insomnia

1. Behavioral versus Pharmacological Therapy for Adult Insomnia Gary K. Zammit, Ph.D. Clinilabs Columbia University College of Physicians and Surgeons

2. Conflict Statement I 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.

3. 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

4. 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.

5. The Definition of Insomnia One or More of the Following Symptoms Must be Present Non-restorative1 or Poor Quality Sleep2 Difficulty Initiating Sleep Difficulty Maintaining Sleep 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 • APA. Diagnostic and Statistical Manual of Mental Disorders - 4th Edition, Text Revision. 2000. • WHO. International Statistical Classification of Diseases and Related Health Problems, 10th Revision, 2006

6. 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.

7. 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 • NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults. J Clin Sleep Med. 2005; 412 - 421 • Colten HR et al. Institute of Medicine of the National Academies. Washington, DC. National Academies Press. 2006.

8. 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 Difficulty falling asleep ~50% Sleep maintenance problems† ~70% Poor sleep quality ~40% Symptoms of individuals who reported sleep disturbances during last 12 months *n=570 †Interrupted sleep and early morning awakening. Leger D et al. Curr Med Res Opin. 2005;21:1785-1792.

9. 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.

10. 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

11. Mild insomnia n = 557 No insomnia n = 801 Severe insomnia n = 264 INSOMNIA DURING 2-YEAR FOLLOW-UPKatz and McHorney, Arch Intern Med, 1998 80 70 60 50 % of subjects 40 30 20 10 0 Baseline status Follow-up status No insomnia Mild insomnia Severe insomnia

12. 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.

13. 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.

14. 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 Insomnia: Often Comorbid Thase ME. Gen Hosp Psychiatry. 2005;27:100-112.

15. 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 QUALITY OF LIFE IN INSOMNIAMETHODS 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.

16. 95 Control Insomnia P<.0001 N=362 75 55 35 General Health Mental Health Role Emotional Role Physical Social Functioning Physical Functioning Body Pain Vitality Burden of Insomnia on Quality of Life Insomnia Impacts Quality of Life SF-36 Scale Score 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.

17. 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.

18. 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

19. Treatments for Insomnia • Pharmacologic treatments • Hypnotics • Behavioral treatments • Sleep hygiene • Stimulus control therapy • Sleep restriction therapy • Cognitive-behavioral therapy • Relaxation therapy • Paradoxical intent

20. 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

21. 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

22. ESZ Observed Placebo Observed ESZ Completers Self-Reported Sleep Onset Latency (SOL) 70 Placebo Completers 60  ESZ LOCF Placebo LOCF 50 40 Median minutes 30 ** ** ** ** ** ** ** 20 10 0 0 1 2 3 4 5 6 Month **P < 0.01; P-values represent within-group pairwise comparisons at each point for all groups. Krystal et al. Sleep. 2003:26;793-799

23. ESZ Observed Placebo Observed ESZ LOCF Placebo LOCF Self-Reported Wake Time After Sleep Onset (sWASO) 60 ESZ Completers Placebo Completers 50 40 Median minutes 30 20 * * * * * * * 10 0 0 1 2 3 4 5 6 Month *P < 0.05; +P = 0.07 for Observed; P-values represent within group pairwise comparisons at each point for all groups. Krystal et al. Sleep. 2003:26;793-799

24. 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

25. Low-Dose Doxepin Reduces WASO *P< 0.05,** p< 0.0001 * * ** **

26. Efficacy of Non-Nightly Zolpidem over 8 Weeks: Self Reported Total Sleep Time * * * * minutes p < .001 for zolpidem-pill vs. placebo-pill * Walsh et al., Sleep, 2000

27. 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

28. Most Common AEs in 5-Week Placebo-Controlled Study of Ramelteon in Adults with Insomnia * All reported AEs ≥ 3% Zammit et al. 2007. Journal of Clinical Sleep Medicine, 3, 495 - 504

29. Low Frequency of Reported Adverse Reactions to Sedative Hypnotics in Hospital Setting • 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;

30. 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

31. 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

32. Potential Residual Memory Effects of Benzodiazepine Hypnotics Roth, et. al., (1980). Psychopharmacology, 70, 231 - 237

33. 70 60 50 40 Improvement 30 20 10 0 Baseline ESZ 3 mg Baseline Placebo Next-Day Psychomotor Functioning Morning DSST Scores^ Score (median) ^Mean of 3 time points (days 1, 15, & 29) Mean +/- 1 SD for age group 35-44 norm – Wechsler adult intelligent scale Zammit et al. Curr. Med. Res. Op., 2004, 20, 1979 - 1991

34. 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

35. Benzodiazepine Use and Risk of Falls1 and Fractures2 in Older Women Relative Risk 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.

36. Postural Instability and Hypnotic UseSensory Organization Test Composite Score SOT Score Change from Baseline Zammit, G. K. 2008. BMC Geriatrics.

37. 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

38. 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

39. Limited Evidence of Withdrawal Effects with Commonly-Prescribed Hypnotics *P < 0.04 Walsh, J., et. al., 2000, Sleep, 23, 1087 - 1096

40. Pentobarbital Methaqualone Diazepam Flunitrazepam Lorazepam GHB Temazepam Zaleplon Eszopiclone Triazolam Zopiclone Flurazepam Zolpidem Estazolam Oxazepam Diphenhydramine Quazepam Trazodone Ramelteon Score Relative Abuse Liability of 19 Hypnotics Griffiths R, Johnson M. 2005, J Clin Psychiatry, 66 (suppl 9): 31 - 41

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

42. Treatment Considerations

43. 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

44. 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

45. 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

46. 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

47. Behavioral Therapy Reduces WASO Edinger, J., et. al., 2006, JAMA, 285, 1856 - 1864

48. Behavioral Therapy & Co-Morbid Insomnia • Chronic pain: • SOL, WASO, SE improved following CBT versus control1 • SOL reduced from 55 minutes to 28 minutes • 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 • 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

49. 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

50. Brief Behavioral Treatment for InsomniaOutcome After Four Weeks of Treatment (P<.001) Buysse, D., et. al., Archives of Internal Medicine, 2011, e-pub January 24, 2011