1. Insomnia Treatment in Brief Project ECHO February 18, 2016 Jonathan Emens, M.D. Associate Professor, Departments of Psychiatry and Internal Medicine Oregon Health & Science University Staff Physician and Sleep Program Director Portland VA Medical Center Portland, OR emensj@ohsu.edu

2. A quick note on the placebo effect Detke MJ et al., J. of Psychiatric Res. 2002; 36:383-390. Calloca et al., Pain 2013; 154: 511-514. Zhang et al., Int J of Neuropsychopharm 2013; 16:849-856. Starting HAM-D 17 score of ~20 8-13 = mild 14-18 = moderate > 19 = severe -8.3 -10.5

3. Smith MT et al., Am J Psych. 2002;159:5-11 Buysee JAMA 2013;309: 706-716 Krystal AD et al., Sleep. 2008;31:79-90. Glass et al. J Clin Psychopharm 2008; 28: 182-188 Krystal, et al. Sleep 2010; 33:1553-61 Michelson et al. Lancet Neurol 2014; 13: 461-471 Morin CM, et al. JAMA 1999;281:991-9 Jacobs GD, et al. Arch Intern Med 2004;164:1888-1896 Treatment: Efficacy (Pharmacologic & Behavioral) VariableAverage Improvement (consider study length and how measured – PSG vs. diary) Sleep Latency~15 to 30 minutes faster Number of Awakenings~ one less awakening Total Sleep Time~20-60+ minutes more sleep

4. Winkleman NEJM 2015;373:1437-1444 For more detailed review: Buysee JAMA 2013;309: 706-716 Treatment: Pharmacologic Antihistamines?

5. Drug Classes Benzodiazepine Receptor Agonists (BzRAs) –Benzodiazepines –Non-Benzodiazepines GABA A agonists Sedating Antidepressants Sedating Antipsychotics Antihistamines Suvorexant (orexin antagonist) Gamma-Hydroxybutyrate (GHB) Melatonin and Melatonin agonists, Gabapentin, Valerian

6. BzRAs: zolpidem ER 12.5 mg of zolpidem ER increased total sleep time (sleep diary) by ~110 minutes over 6 months Placebo increased total sleep time by ~85 minutes Difference of ~25 minutes Krystal AD et al., Sleep. 2008;31:79-90.

7. BzRAs: benzodiazepines Glass et al. J Clin Psychopharm 2008; 28: 182-188 15 mg of temazepam increased total sleep time (sleep diary) by 1.0 hours over 2 weeks Placebo increased total sleep time by 0.4 hours Difference of 0.6 hours

8. Treatment: Pharmacologic Benzodiazepine Receptor Agonists (BzRAs) –Benzodiazepines –Non-Benzodiazepines GABA A agonists Sedating Antidepressants Sedating Antipsychotics Antihistamines Suvorexant (orexin antagonist) Gamma-Hydroxybutyrate (GHB) Melatonin and Melatonin agonists, Gabapentin, Valerian

9. Sedating Antidepressants: Doxepin Krystal, et al. Sleep 2010; 33:1553-61 3 mg of doxepin increased total sleep time (PSG) by 46.8 minutes over 3 months Placebo increased total sleep time by 23.1 minutes Difference of 23.7 minutes

10. Treatment: Pharmacologic Benzodiazepine Receptor Agonists (BzRAs) –Benzodiazepines –Non-Benzodiazepines GABA A agonists Sedating Antidepressants Sedating Antipsychotics Antihistamines Suvorexant (orexin antagonist) Gamma-Hydroxybutyrate (GHB) Melatonin and Melatonin agonists, Gabapentin, Valerian

11. Antihistamines: diphenhydramine Glass et al. J Clin Psychopharm 2008; 28: 182-188 50 mg of diphenhydramine increased total sleep time (sleep diary) by 0.7 hours over 2 weeks Placebo increased total sleep time by 0.4 hours Difference of 0.3 hours

12. Treatment: Pharmacologic Benzodiazepine Receptor Agonists (BzRAs) –Benzodiazepines –Non-Benzodiazepines GABA A agonists Sedating Antidepressants Sedating Antipsychotics Antihistamines Suvorexant (orexin antagonist) Gamma-Hydroxybutyrate (GHB) Melatonin and Melatonin agonists, Gabapentin, Valerian

13. Orexin antagonist Michelson et al. Lancet Neurol 2014; 13: 461-471 Suvorexant (30 or 40 mg) increased total sleep time (sleep diary) by 38.7 minutes over one month Placebo increased total sleep time by 16.0 minutes Difference of 22.7 minutes

14. Progressive relaxation EMG biofeedback Guided imagery Stimulus control therapy (in bed only when sleepy, bed/bedroom is for sleep and sex only, get out of bed when unable to sleep) Bed Restriction: fixed waketime, change bedtime by 15 minutes if sleep efficiency >90% in the last week Regular sleep schedule and light/dark schedule Requires the use of a sleep diary Treatment: Behavioral Morin CM, et al. Sleep 2006;29:1398-1414

15. Progressive relaxation EMG biofeedback Guided imagery Stimulus control therapy (in bed only when sleepy, bed/bedroom is for sleep and sex only, get out of bed when unable to sleep) Bed Restriction: fixed waketime, change bedtime by 15 minutes if sleep efficiency >90% in the last week Regular sleep schedule and light/dark schedule Requires the use of a sleep diary Morin CM, et al. Sleep 2006;29:1398-1414 Treatment: Behavioral

16. Buysee JAMA 2013;309: 706-716 Also see: Winkleman NEJM 2015;373:1437-1444 Treatment: Behavioral

17. Treatment: Comparisons

18. Similar efficacy pharmocologic vs. cognitive-behavioral treatments in several studies 8 weeks of CBT vs. temazepam (7.5-30 mg) vs. combined treatment. CBT maintained improved sleep at 3, 12, and 24 months. ~6 weeks of CBT vs. zolpidem (5-10mg) vs. combined treatment. CBT generally better than zolpidem. Morin CM, et al. JAMA 1999;281:991-9 Jacobs GD, et al. Arch Intern Med 2004;164:1888-1896 Morin CM, et al. Sleep 2006;29:1398-1414

19. Treatment: Comparisons Morin CM, et al. JAMA 1999;281:991-9 8 weeks of: temazepam (7.5-30 mg, avg=20 mg), placebo, CBT-I (8x90 min.), or combination. Temazepam increased total sleep time by 43.7 min. CBT-I increased total sleep time by 30.5 min. and by 65.2 min. at 2 years Combo increased total sleep time by 42.2 min. Placebo increased total sleep time by 19.7 min.

20. Treatment: Comparisons Jacobs GD, et al. Arch Intern Med 2004;164:1888-1896 6 weeks of: zolpidem (10 mg x 4 wks, 5 mg x 1 wk, 5 mg q o night x 1 wk), placebo, or CBT-I (4x30 min. and 1x15 min sessions). Sleep diary (2 weeks). zolpidem increased total sleep time by 39.7 minutes after 4 weeks (vs 69.2 minutes after taper) CBT-I increased total sleep time by 48.6 minutes Placebo increased total sleep time by 29.5 minutes

21. Smith MT et al., Am J Psych. 2002;159:5-11. Treatment: Comparisons

22. Smith MT et al., Am J Psych. 2002;159:5-11. Treatment: Comparisons

24. VA CBT-I Group Kate Chiba, LCSW

25. VA CBT-I Group Week1: Introduction to CBT-I sleep diaries and home practice discussion of current sleep issues goals: fall asleep faster, wake up less, get more hours of sleep, feel more rested in the morning or all of the above? Week 2: Biology of Sleep Sleep drive 24-hour body clock and the importance of light Week 3: Starting Treatment history of sleep things that get insomnia started and things that keep it alive Bed Restriction Stimulus Control Week 4: Experience with Treatment What works and what doesn’t? Barriers to stimulus control and bed restriction Week 5: Thoughts & Feelings about sleep, Part I “The Buffet” Pros and Cons Week 6: Thoughts & Feelings about sleep, Part II Radical Acceptance Automatic thought monitoring Mindfulness stress reduction Week 7: Continuing Treatment Challenges of bed restriction, stimulus control and regular light/dark schedule Image Rehearsal Therapy for Nightmares (if group is interested) Week 8: Final Session Relapse prevention and loose ends

29. From: Kryger, Roth, Dement, eds., Principles and Practice of Sleep Medicine, 2011

31. 1. Keep a sleep diary throughout the treatment period. 2. First work on keeping the same lights out & lights on schedule. Keep the same bedtimes and out-of-bed times on weekends and weekdays. Get help from family or friends in getting out of bed at the same time each day. 3. If you start with 6 hours of bed restriction, determine your starting “lights out” time by subtracting 6 hours from your chosen wake time. 4. If you are able to obtain good sleep (that is, about 90% of the time you are in bed is sleep) for three days, add on 15 minutes of time in bed. Add on the additional time in bed at the beginning of the night, keeping your wake time the same. 5. Every three days reevaluate: if you are obtaining good sleep add on another 15 minutes of time in bed. If insomnia returns, subtract 15 minutes of time in bed. 6. Make sure you get as much rest as you need during your wake/lights on time. Starting Lights out/In Bed: __________________________ Lights On/Out of Bed: __________________________ 1. The goal of stimulus control is to have your brain think the bed is a place to sleep instead of a place to be awake. 2. The bed is for sleep and sleep is for the bed. Go to bed only when you are sleepy. 3. If you don’t fall asleep in 15 to 20 minutes, get up, go into another room (if possible), and lay quietly in darkness until sleepy. This other place is your “insomnia bed.” Try listening to music, a book on tape, or the radio. 4. Don’t watch the clock. Just guess when 15-20 minutes have passed. Plan ahead of time what you are going to do during the time you are out of bed. Bed Restriction Stimulus Control

32. RADICAL ACCEPTANCE “Radical Acceptance” means acknowledging what already is. “Radical Acceptance” doesn’t mean that you like or approve of the situation. It doesn’t mean it’s fair, or the way things “should” be. It doesn’t mean that the situation is any less bad than you think it is. Radical acceptance simply means that you stop fighting reality. By accepting reality, acknowledging the way things are, we then have a basis for defining what the options are, and making a plan to change the things we have the power to change. By accepting reality, we can stop wasting energy trying to change the things we cannot change. Radical acceptance IS difficult – but it’s worth the effort. Accepting reality can bring us peace of mind, even when the situation is bad.

37. The End

38. Extra Slides

39. Treatment: Pharmacologic Benzodiazepine Receptor Agonists (BzRAs) –Benzodiazepines –Non-Benzodiazepines GABA A agonists Sedating Antidepressants Sedating Antipsychotics Antihistamines Suvorexant (orexin antagonist) Gamma-Hydroxybutyrate (GHB) Melatonin and Melatonin agonists, Gabapentin, Valerian Gimenez et al. Psychopharm 2007; 190: 507-516 Tassniyom et al. J Med Assoc Thai 2010; 93: 729-34

40. Antipsychotics 25 mg of Quetiapine increased total sleep time (sleep diary) by 124.9 minutes over 2 weeks Placebo increased total sleep time by 72.2 minutes Difference of 52.7 minutes Tassniyom et al. J Med Assoc Thai 2010; 93: 729-34

41. Treatment: Reviews Buysee JAMA 2013;309: 706-716

42. Treatment: Hypnotic Reviews Buysee JAMA 2013;309: 706-716

43. Treatment: CBT Reviews Buysee JAMA 2013;309: 706-716