TREATMENT OF DSPD and SHIFT WORK DISORDER

Transcription

1 TREATMENT OF DSPD and SHIFT WORK DISORDER James K. Wyatt, Ph.D., D. ABSM, C.BSM, FAASM Director, Section of Sleep Disorders and Sleep-Wake Research Rush University Medical Center Associate Professor of Behavioral Sciences Rush Medical College SBSM WEBINAR, 26 JULY 2017

2 Educational Objectives By the end of this presentation, learners will be able to: Describe circadian and homeostatic modulation of sleep, and apply these to their own patients Implement evident-based or rational treatment approaches for patients with CRSD

3 Basic modulation of sleep and wakefulness The 2-process model of sleep-wake regulation, from Borbély, Daan, & Beersma

4 HOMEOSTATIC COMPONENT (how long have you been awake) High H Slow buildup Rapid drop Low H Borbély, Hum Neurobiol, 1982; Borbély et al model, HFSP, 2000

5 CIRCADIAN COMPONENT (biological day vs. night) CSMZ: sleep 3,4 WMZ: wake 1,2 1 Strogatz et al., Am J Physiol 253, Lavie, Electroencephalogr. Clin. Neurophysiol 63, Stepanski & Wyatt, Sleep Medicine Reviews 7, Wyatt et al., Sleep 27, 2004

6 2-PROCESS MODEL OF SLEEP-WAKE REGULATION (aka, a 4-person relay race) Borbély, Hum Neurobiol, 1982; Borbély et al model, HFSP, 2000

7 HOMEOSTATIC IMPLICATIONS FOR CIRCADIAN SLEEP DISORDERS Naps Decrease homeostatic drive Delays sleep onset, lighter sleep Good for shift work (2/2 short daytime sleep) Bad for DSPD (need the homeostatic drive for SOL) Late wake times Shorter duration of subsequent wake Lower homeostatic drive for sleep initiation and consolidation (DSPD on weekends) Shorter sleep duration EDS, fatigue, cognitive and mood dysfunction DSPD on weekdays, shift workers at night

8 CAFFEINE 1 Wyatt, et al, Sleep, Landolt, et al, Neuropsychopharmacology, Landolt, et al, Brain Res., 1995 THE GOOD: 3-7 hr half life Adenosine receptor antagonist (adenosine builds during wake) Attenuates the expression of sleep homeostatic pressure Good for homeostatic-related (not circadian) cognitive deficits with extended wakefulness1 (jet lag, shift work) THE BAD: May increase sleep latency 2 Suppresses slow wave activity (deep sleep) 3 sensitivity : insomnia, nervousness, irritability, tachycardia

9 Stable sleep-wake schedule = Stable light-dark schedule = Optimal entrained circadian phase Wyatt, 2013 NORMAL SLEEPERS Minimal Shifting Effect for Midday Light Evening / Early Night Light Phase Delay (move later) C R O S S O V E R Z O N E Early morning / After wake time Phase Advance (move earlier) 12pm WT 12am BT 8am WT 12pm WT

10 PHASE RESPONSE CURVE for EXOGENOUS MELATONIN(The Melatonin PRC ) Late Afternoon/ Early Evening MEL Possible Sedation during sports, homework, after school job Phase Advance (move earlier) C R O S S O V E R Z O N E Late night / Early morning Phase Delay (move later) 12pm WT 12am BT 8am WT 12pm WT NOTE: Clock times denote only to habitual sleep schedule for sample patient, not to absolute clock time for all Melatonin PRC, see: Lewy, et al, Chronobiol. Int., 1998; Burgess et al., J Physiol, 2008 Wyatt, 2008

11 Wyatt et al., Sleep, 2006 MELATONIN AS A CIRCADIAN PHASE-DEPENDENT HYPNOTIC

12 ICSD-3: Circadian rhythm sleep-wake disorders

13 TREATMENT OPTIONS

14 CRSD TREATMENT OPTIONS 1 Identify the homeostatic and circadian contributions to sleep/wake complaints 2 Fight the EDS Caffeine (not great for children) Stimulants / Alerting Agents (not great for children) Prevent or encourage napping 3 Put you to sleep Melatonin / melatonin agonists Hypnotics (not great for children) 4 Shift circadian phase Melatonin Phototherapy [light and blocking light] Sleep scheduling (e.g., chronotherapy, naps, no naps)

15 UPDATE FROM 2015 (Auger et al.) DSPD The TF suggests that clinicians treat DSWPD in adults with and without depression with strategically timed melatonin (versus no treatment). [WEAK FOR] The TF suggests that clinicians treat children and adolescents with DSWPD (and no comorbidities) with strategically timed melatonin (versus no treatment). [WEAK FOR] The TF suggests that clinicians treat children and adolescents with DSWPD comorbid with psychiatric conditions with strategically timed melatonin (versus no treatment). [WEAK FOR] The TF suggests that clinicians treat children and adolescents with DSWPD with post-awakening light therapy in conjunction with behavioral treatments (versus no treatment). [WEAK FOR]

16 PATIENT EDUCATION POINTS: DSPD Example Naps lower homeostatic drive, hence SO insomnia Example: afterschool naps, then SO insomnia Late wake time, then early bedtime Shorter duration of sustained wakefulness Insufficient homeostatic drive to fall asleep Example: Sunday night insomnia Late sleep onset, then early wake time Shorter duration of sleep Higher EDS from leftover homeostatic sleep drive Example: school nights

17 DECISIONAL BALANCE [for secondary gain / motivated DSPD subtype] WHAT ABOUT HAVING THIS SLEEP PROBLEM IS: BAD NEUTRAL GOOD

18 SLEEP SCHEDULING When to sleep and when not to sleep Chronotherapy progressive shift of S-W schedule (DSPD, ASPD) Enforcing a daily S-W cycle vs. patient s ad lib schedule (free-running, irregular) Major sleep episode with scheduled napping (jet lag, shift work)

19 CHRONOTHERAPY [indicated: option for DSPD] Wyatt, 2008 Pre 1 Pre 2 Pre 3 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 3hr DELAY OF BT/WT SCHEDULE BASELINE / STABILIZATION Day 7 Post 1 Post 2 Post 3 Post 4 SMALLER SHIFT IF REQUIRED RIGID ADHERENCE TO SLEEP SCHEDULE 12am 3am 6am 9am 12pm 3pm 6pm 9pm 12am NOTE: Clock times denote only to habitual sleep schedule for sample patient, not to absolute clock time for all modified from Czeisler et al., Sleep, 1982

20 DSPD Wyatt, Sleep Medicine Clinics, 2007 PHOTOTHERAPY [indicated: guideline for DPSD] Need to advance phase to an earlier hour Light exposure in the morning (see PRC) natural light, artificial bright light NO STANDARD PROTOCOL; I suggest: stabilize S-W schedule x 3 days start 60+ min. light, starting at late wake time dose of 2,000-10,000 lux 30 min. per day advance of BT/WT schedule 30 min. per day advance of light onset *** dim light in the evening (prevent phase delay) 30 min. maintenance dose of light at wake time evaluation by ophthalmologist if? ocular risk

21 PREVENT FURTHER PHASE DELAY Block evening blue light, 2hrs prior to BT Avoid daylight bulb use in evenings Dim the lighting, TV, e-devices f.lux or other computer app "Night shift on iphone, ipad, laptops and desktops

22 PHOTOTHERAPY Wyatt, 2008 [indicated: guideline] Pre 1 Pre 2 Pre 3 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Post 1 Post 2 12am BASELINE / STABILIZATION 1. 30min. ADVANCE OF BT/WT SCHEDULE PER DAY 2. 60min. BRIGHT LIGHT AT WT 3. 2hr DIM LIGHT PRIOR TO BT STRICT SLEEP SCHEDULE 30min. MAINTENANCE LIGHT 3am 6am 9am 12pm 3pm 6pm 9pm 12am NOTE: Clock times denote only to habitual sleep schedule for sample patient, not to absolute clock time for all Wyatt, Sleep Medicine Clinics, 2007

23 Morning light exposure occurs in the region of maximal phase delays for DSPD patients likely MAINTAINING the phase delay Wyatt, 2013 DSPD PATIENTS Minimal Shifting Effect for Midday Light Evening / Early Night Light Phase Delay (move later) R I D E T O S C H O O L C R O S S O V E R Z O N E Early morning / After wake time Phase Advance (move earlier) 3pm WT 3am BT 11am WT 3pm WT

24 Gradisar et al., Sleep, 2011 RCT: CBT + PHOTOTHERPY DSPD Age 11-18, DSPD diagnosis CBT (n=23) sleep education (Session 1) heavy cognitive component (Sessions 2-5) Wrap-up (Session 6) minutes of post-awakening light of 1,000 lux or sunlight 30min phase advance of sleep schedule/day Wait list control (n=17) Daily sleep diary Wrist actigraphy: insufficient data

25 Gradisar et al., Sleep, 2011 RESULTS DSPD School night sleep 56 minute decrease in sleep latency 38 minute earlier sleep onset time 60 minutes more total sleep time 26 minute earlier wake-up time Some improvement in weekend sleep Good maintenance of gain at 6 months Improved EDS and fatigue See also: Danielsson et al., 2015, BSM: RCT of CBT+Light: decreased anxiety and depression

26 MELATONIN phase shifting Max phase advance: give 5 hr prior to DLMO 1 DLMO is ~1.5 to 2 hr. prior to BT DSPD Relapse reported as high after stopping in clinical trials May have to be a chronic treatment? if really just phase-dependent hypnotic effect Sedation concern with afternoon (phase advancing) or morning (phase delaying) dosing Neuroendocrine concern for use in young children & adolescents Different risk : benefit evaluation with severe neurodevelopmental disorders 1 Burgess et al., 2008, J Physiol

27 MELATONIN Wyatt, 2008 [indicated: guideline] Pre 1 Pre 2 BASELINE / STABILIZATION Pre 3 Day 1 Day 2 Day 3 Day 4 Day min. ADVANCE OF BT/WT SCHEDULE PER DAY Day 6 Day 7 2. MELATONIN 15-30min. PRIOR TO BT Day 8 Day hr DIM LIGHT PRIOR TO BT Day 10 Post 1 Post 2 9pm 12am 1. STRICT SLEEP SCHEDULE 2. MAINTAIN MELATONIN 3am 6am 9am 12pm 3pm 6pm 9pm NOTE: Clock times denote only to habitual sleep schedule for sample patient, not to absolute clock time for all

28 MELATONIN FOR DSPD DSPD Meta-analysis of 9 suitable studies mg Fixed time, time range, or X hours prior to DLMO Up to 4 weeks n s =8 to 105 Mix of sleep diary, actigraphy, PSG Most measured DLMO van Geijlswijk et al., Sleep, 2010

29 META-ANALYSIS RESULTS DSPD Adults DLMO advanced 1.69 hours (1.13 hr/children) Sleep onset time 0.7 hours (0.64 hr/children) Wake-up time earlier in children only Sleep latency shorter in only in children Total sleep time increased only in children Most studies didn t advance dose timing van Geijlswijk et al., Sleep, 2010

30 DSPD: PHOTOTHERAPY + MELATONIN DSPD N-40, age 16-25, DSPD 2 weeks: DL+PLA, BL+PLA, DL+MEL, BL+MEL All: gradual advance of WT 1hr/day 3 months open label, BL+MEL or no tx ALL GROUPS: advance of BT, WT, DLMO High relapse rate with no treatment f/u Good durability with long-term treatment Saxvig et al., 2013, Chronobiol Intl; Wilhelmsen-Langeland et al., 2013, JRB

31 SHIFT WORK SLEEP DISORDER Nap during night or extended shifts [indicated: standard] Short nap during meal breaks 1-2hr nap prior to evening/night shift Hypnotic for day sleep [indicated: guideline] Melatonin for daytime sleep periods Recovery sleep rebound sleep, telephone & doorbell off, protected sleep time (kids, pets) catch up prior to next night shift

32 SHIFT WORK Caffeine (e.g., Jim Walsh) Diminishes certain cognitive deficits Risk of suppressing sleep depth Sleep environment (e.g., Katie Sharkey) Dark shades, comfortable temperature, no interruptions, phone off Error detection systems, redundancy Light exposure at work for stimulatory effect Don t work shifts some individuals are more intolerant of shift work

33 40min nap at 0300 x = 25mins of sleep

34 PLANNED NAPPING BEFORE (or during) NIGHT SHIFT (standard) 1-2 hour nap, to end at least 1 hour prior to night shift Caffeine may be helpful (option) Modafinil 1hr prior to night shift (guideline) Schweitzer et al., Sleep, 2006

35 q hs MELATONIN AS A CIRCADIAN PHASE-DEPENDENT HYPNOTIC: Applications for daytime sleep Wyatt et al., Sleep, 2006

36 MODAFINIL (Provigil) Non-amphetamine wake-promoter 15hr ½ life (really 2 components) RCTs for Shift Work Sleep Disorder 1 200mg, 1hr prior to shift No food +/- 1hr of dosing Approved indication FDA rejected indication for treatment of sleepiness in general MSLT: less sleepy (p < 0.01) CGI: less impaired (p < ) Nuvigil 150mg: even better results 2 (15hr ½ life) 1 Czeisler et al., 2005, NEJM 353: Czeisler et al., 2009, MayoClinProc 84:958-72

37 CONCLUSION We have very few BEST practices for treating the circadian rhythm disorders more research is needed

38 Recommended reading (in addition to the ICSD-3) Auger RR et al. Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24- Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for JCSM (10) Morgenthaler TI et al. Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep Nov 1;30(11): Sack RL et al. Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Academy of Sleep Medicine review. Sleep Nov 1;30(11): Sack RL et al. Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review. Sleep Nov 1;30(11):

39 DIAGNOSTIC CRITERIA ICSD-3 from AASM [skipping this section for webinar useful for online posting]

40 INTERNATIONAL CLASSIFICATION OF SLEEP DISORDERS - 3 Circadian workgroup Phyllis Zee (chair) Robert Auger Makoto Uchiyama Ken Wright James Wyatt Steve Lockley (consultant) Judy Owens (consultant) Significant addition of wake to the titles Developmental implications highlighted in each disorder (Judy Owens!)

41 General Criteria for Circadian Rhythm Sleep-Wake Disorder A chronic or recurrent pattern of sleep-wake rhythm disruption due primarily to an alteration of the circadian timing system or to a misalignment between the internal circadian rhythm and the sleep-wake schedule desired or required by an individual s physical environment or social/work schedules. The circadian rhythm disruption leads to insomnia symptoms, excessive sleepiness, or both. The sleep and wake disturbances cause clinically significant distress or impairment in mental, physical, social, occupational, educational, or other important areas of functioning. ICSD-3

42 ASSESSMENT TOOLS Sleep diary Required for most Wrist actigraphy Strongly encouraged Chronotype assessment May be helpful Circadian phase assessment (CBT, DLMO, amt6s) On the horizon

43 FIGURE FROM: Lewy & Sack, Neuropsychopharmacology, 2002 DLMO

44 10 minute difference on average Burgess et al, Sleep, 2015

45 CHRONOTYPE VS. DLMO Kantermann, Sung, & Burgess 2015, JBR Munich Chronotype Questionnaire Morningness Eveningness Questionnaire Age Vs. DLMO 36 controls, 24 DSPD 4hr range in the DLMO was observed at a given (questionnaire) score Chronotype score NOT TO BE USED to time treatments

46 Delayed Sleep-Wake Phase Disorder There is a delay in the phase of the major sleep episode in relation to the desired or required sleep time and wake-up time, as evidenced by a chronic or recurrent complaint by patient or caregiver of inability to fall asleep and difficulty awakening at a desired or required clock time. The symptoms are present for at least three months. When patients are allowed to choose their ad libitum schedule, they will exhibit improved sleep quality and duration for age and maintain a delayed phase of the 24- hour sleep-wake pattern. Sleep log and, whenever possible, actigraphy monitoring for at least seven days (preferably 14 days) demonstrates a delay in the timing of the habitual sleep period. Both work/school days and free days must be included within this monitoring. Not better explained by another current sleep disorder, medical or neurological disorder, mental disorder, medication use, or substance use disorder. ICSD-3

47 DSPD Subtype: motivated delayed sleep phase disorder a subgroup typically comprised of adolescents who have little intrinsic motivation to successfully complete treatment and thereby resume a normal lifestyle (regular school attendance, developmentally appropriate peer interactions, etc.) Psychiatric comorbidity is high Factors to avoid school (e.g., learning disability) Exaggerated parental response of inability to awaken with extreme measures ICSD-3

48 Shift Work Disorder There is a report of insomnia and/or excessive sleepiness, accompanied by a reduction of total sleep time, which is associated with a recurring work schedule that overlaps the usual time for sleep. The symptoms have been present and associated with the shift work schedule for at least three months. Sleep log and actigraphy monitoring (whenever possible and preferably with concurrent light exposure measurement) for at least 14 days (work and free days) demonstrates disturbed sleep and wake pattern. The sleep and/or wake disturbance are not better explained by another current sleep disorder, medical or neurological disorder, mental disorder, medication use, poor sleep hygiene, or substance use disorder. Approximately 10% prevalence in night/rotating Also: (Wyatt)

49 SHIFT WORK DISORDER Shift work = any work outside the 7AM-6PM window Shorter daytime sleep episodes = sleepiness Working during biological night = sleepiness Impaired cognition and performance GI distress Irritability / mood lability Abuse of stimulants for sleepiness Abuse of alcohol for sleep Treatment with melatonin, hypnotics, and/or wakepromoting agents Optimizing and scheduling sleep and napping CIRCADIAN MISALIGNMENT

50 Futenma et al., Sleep Medicine 2015: SAFETY RISKS OF HYPNOTIC USE Increased risk with multiple hypnotics 6.9% single hypnotic, 3.1% multiple hypnotics Only SWSD predicted multiple hypnotic use (OR 2.8)

51 [ask about] PARASOMNIAS in ROTATING SHIFT WORKERS N = 2,198 nurses in Norway Higher confusional arousals (vs. day only: day/evening: OR 2.10 and day/evening/night: OR 1.71) Nightmares (vs. day only: day/evening: OR 1.64 and day/evening/night: OR 1.57) Only night shift = no change in parasomnia incidence Bjorvatn et al., Chronobiol Int 2015; 32(10):1352-8

52 Consequences of Shift Work