Delayed sleep-wake phase disorder and shift work James K. Wyatt, Ph.D., D. ABSM, FAASM Director, Section of Sleep Disorders and Sleep-Wake Research Rush University Medical Center Associate Professor of Behavioral Sciences Rush Medical College Associated Professional Sleep Societies, LLC 1
X Conflict of Interest Disclosures for Speakers 1. I do not have any relationships with any entities producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients, OR 2. I have the following relationships with entities producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients. Type of Potential Conflict Details of Potential Conflict Grant/Research Support Consultant Speakers Bureaus Financial support Other 3. The material presented in this lecture has no relationship with any of these potential conflicts, OR 4. This talk presents material that is related to one or more of these potential conflicts, and the following objective references are provided as support for this lecture: 1. 2. 3. Associated Professional Sleep Societies, LLC 2
CONCLUSION We have very few BEST practices for treating the pediatric circadian rhythm disorders more research is needed Associated Professional Sleep Societies, LLC 3
Educational Objectives By the end of this presentation, learners will be able to: describe circadian and homeostatic modulation of sleep to patients, and implement interventions for insomnia symptoms based on these complaints implement cognitive-behavioral treatment components for DSPD and shift work disorder Associated Professional Sleep Societies, LLC 4
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 2015. JCSM. 2015 11(10)1199-1236 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. 2007 Nov 1;30(11):1445-59. 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. 2007 Nov 1;30(11):1460-83. 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. 2007 Nov 1;30(11):1484-501. Associated Professional Sleep Societies, LLC 5
SLEEP HOMEOSTASIS During each hour you are awake ( cost of being awake): Sleep-promoting substances build up in the brain (e.g. adenosine) Wake-promoting substances are used up in the brain (e.g., NE, 5-HT) During sleep Sleep-promoting substances are cleared Wake-promoting substances are replenished Associated Professional Sleep Societies, LLC 6
INTRINSIC CIRCADIAN TIMEKEEPING SYSTEM 24-hour clock in the brain Suprachiasmatic nucleus (the SCN ) Biological day vs. biological night Regulates timing of (for example): Core body temperature Appetite Amount of urine production Alertness / sleepiness Coordinates clocks throughout the body Associated Professional Sleep Societies, LLC 7
2-PROCESS MODEL OF SLEEP-WAKE REGULATION (aka, a 4-person relay race) Borbély, Hum Neurobiol, 1982; Borbély et al model, HFSP, 2000 Associated Professional Sleep Societies, LLC 8
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 C R O S S O V E R Early morning / After wake time 12pm WT Phase Delay (move later) 12am BT Z O N E Phase Advance (move earlier) 8am WT 12pm WT Associated Professional Sleep Societies, LLC 9
PHOTOTHERAPY DURING SLEEP 2msec flash 3,000 lux (eyes closed, so around 300 lux) Every 30 sec From 2-3hr after bedtime 30 min phase delay Zeitzer JM et al, 2014, JBR Associated Professional Sleep Societies, LLC 10
Evening reading: 4 hours of pre-bedtime ipad vs. book Change A M et al, 2015, PNAS Associated Professional Sleep Societies, LLC 11
Real life trumps laboratory in matters of public health That is, the light emitted from the ereaders would have had a much smaller effect in alerting the brain than they would have had the participants been exposed to a normal pattern of everyday light exposure before using the ereaders before bedtime. Thus, the question still remains as to whether the light being emitted from an ereader, or any other type of electronic device, would actually impact nocturnal alertness and sleep in normally behaving individuals. Zeitzer JM, 2015, PNAS Reply to Zeitzer: Good science, in or out of the laboratory, should prevail Change A M et al, 2015, PNAS Associated Professional Sleep Societies, LLC 12
PHASE RESPONSE CURVE for EXOGENOUS MELATONIN(The Melatonin PRC ) Late Afternoon/ Early Evening MEL 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 Associated Professional Sleep Societies, LLC 13
Wyatt et al., Sleep, 2006 MELATONIN AS A CIRCADIAN PHASE-DEPENDENT HYPNOTIC Associated Professional Sleep Societies, LLC 14
MORNING LIGHT + AFTERNOON MELATONIN IN 18-40yo GOOD SLEEPERS 0.5mg melatonin 5hr prior to BT Sleep schedule 1hr earlier/day 2hr = 30min on/off 1hr = 15min on/off 0.5hr = 30min at WT 1.8hr phase advance in 0.5hr group Crowley & Eastman, 2015, Sleep Medicine Associated Professional Sleep Societies, LLC 15
HOMEOSTATIC IMPLICATIONS FOR CIRCADIAN SLEEP DISORDERS Naps Decrease homeostatic drive Delays sleep onset, lighter sleep Good for shift work and jet lag (+ 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 Associated Professional Sleep Societies, LLC 16
CAFFEINE 1 Wyatt, et al, Sleep, 2004 2 Landolt, et al, Neuropsychopharmacology, 1995 3 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 Associated Professional Sleep Societies, LLC 17
ICSD-3: CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS Associated Professional Sleep Societies, LLC 18
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 Associated Professional Sleep Societies, LLC 19
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 Associated Professional Sleep Societies, LLC 20
FIGURE FROM: Lewy & Sack, Neuropsychopharmacology, 2002 DLMO Associated Professional Sleep Societies, LLC 21
HOME DLMO ASSESSMENT N=35, 21-62yo good sleepers (DSPD paper under review) HOME/LAB or LAB/HOME, 5 days, then opposite order 6hrs prior to mean BT until 2hrs after Every 30 minutes Detailed orientation Cotton in compliance-monitoring container Light meter to ensure dim light Burgess et al, Sleep, 2015 Associated Professional Sleep Societies, LLC 22
Burgess et al, Sleep, 2015 10 minute difference on average Associated Professional Sleep Societies, LLC 23
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 Associated Professional Sleep Societies, LLC 24
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 Associated Professional Sleep Societies, LLC 25
ASSOCIATED FEATURES DSPD and evening types Higher rates of psychiatric disorders E.g., mood disorders, suicide risk Potential overlap/alternation with free running disorder KEY POINT: can develop conditioned (or other) insomnia over time both may require treatment ICSD 3 Associated Professional Sleep Societies, LLC 26
PREVALENCE OF DSPD 374 Australian teens Sleep diary + actigraphy + questionnaires DSPD: 1% 1 ICSD2 criterion: 52% 2 ICSD2 criteria: 14% 0 ICSD2 criteria: 33% Differentiation of evening type vs. delayed phase vs. delayed sleep vs. DSPD Lovato et al., 2013, JCSM Associated Professional Sleep Societies, LLC 27
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 Associated Professional Sleep Societies, LLC 28
DECISIONAL BALANCE WHAT ABOUT HAVING THIS SLEEP PROBLEM IS: BAD NEUTRAL GOOD Associated Professional Sleep Societies, LLC 29
Hysing et al., BSM 2015 Oct, 1 15 DSPD vs. ADHD N=9,846 (age 16-19) in Norway Higher vs. lower ADHD symptoms: Increased risk of DSPD (7.6% vs. 2.8%) Increased insomnia (33.7% vs. 11.4%) Possible bidirectional relationship between impaired sleep and ADHD Suggest targeting sleep in ADHD diagnosis and treatment Associated Professional Sleep Societies, LLC 30
Siversten et al., Sleep Med. 2015;16(9):1084 90 POOR ACADEMIC PERFORMANCE IN DSPD Associated Professional Sleep Societies, LLC 31
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. Associated Professional Sleep Societies, LLC 32
INSOMNIA IN SHIFT WORKERS N = 1,586 nurses in Norway Evening shift insomnia Higher in 2-shift and 3-shift rotation: 29.8% vs 19.8% Night shift insomnia Higher in 3-shift than only night workers: 67.7% vs 41.7% Off-night insomnia permanent night workers 11.4% 2-shift rotators: 4.2% 3-shift rotators: 3.6% Flo et al., Occup Environ Med 2013; 70(4):238 45 Associated Professional Sleep Societies, LLC 33
CHRONOTYPE vs. SHIFT WORK Old thought: evening types did better at shift work Higher use of hypnotics in evening-type shift workers (Futenma et al., Sleep Medicine 2015: 16(5):604-11) Worse sleep quality (Yazdi et al., Work 2014; 47(4):561-7) Worse sleep on day and night shifts (Martin et al., Chronobiol Int 2015; 32(5):627-36) TAKE HOME: Don t be an evening chronotype and engage in shift work Associated Professional Sleep Societies, LLC 34
SAFETY RISKS OF HYPNOTIC USE Increased risk with multiple hypnotics Futenma et al., Sleep Medicine 2015: 604 11 6.9% single hypnotic, 3.1% multiple hypnotics Only SWSD predicted multiple hypnotic use (OR 2.8) Associated Professional Sleep Societies, LLC 35
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 Associated Professional Sleep Societies, LLC 36
TREATMENT OPTIONS: APPLICATIONS FOR DSPD Associated Professional Sleep Societies, LLC 37
UPDATE FROM 2015 (Auger et al.) ASWPD: The TF suggests that clinicians treat adult ASWPD patients with evening light therapy (versus no treatment). [WEAK FOR] N24SWD The TF suggests that clinicians use strategically timed melatonin for the treatment of N24SWD in blind adults (versus no treatment). [WEAK FOR] 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] Associated Professional Sleep Societies, LLC 38
2015 UPDATE: CONTINUED ISWRD The TF suggests that clinicians treat ISWRD in elderly patients with dementia with light therapy (versus no treatment). [WEAK FOR] The TF recommends that clinicians avoid the use of sleep-promoting medications to treat demented elderly patients with ISWRD (versus no treatment). [STRONG AGAINST] The TF suggests that clinicians avoid the use of melatonin as a treatment for ISWRD in older people with dementia (versus no treatment). [WEAK AGAINST] The TF suggests that clinicians use strategically timed melatonin as a treatment for ISWRD in children/adolescents with neurologic disorders (versus no treatment). [WEAK FOR] The TF suggests that clinicians avoid the use of combined treatments consisting of light therapy in combination with melatonin in demented, elderly patients with ISWRD (versus no treatment). [WEAK AGAINST] Associated Professional Sleep Societies, LLC 39
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 Sleep scheduling (e.g., chronotherapy, naps, no naps) Associated Professional Sleep Societies, LLC 40
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 Associated Professional Sleep Societies, LLC 41
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) Associated Professional Sleep Societies, LLC 42
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 Day 7 Post 1 Post 2 Post 3 Post 4 3hr DELAY OF BT/WT SCHEDULE BASELINE / STABILIZATION 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 Associated Professional Sleep Societies, LLC 43
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 Associated Professional Sleep Societies, LLC 44
1hr light pulse = ~ 30 min phase advance 1+ hr phase delay St Hilaire et al., J Physiol, 2010 Associated Professional Sleep Societies, LLC 45
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 PHOTOTHERAPY [indicated: guideline] 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, 2008 Wyatt, Sleep Medicine Clinics, 2007 Associated Professional Sleep Societies, LLC 46
Morning light exposure occurs in the region of maximal phase delays for DSPD patients likely MAINTAINING the phase delay Wyatt, 2013 DSPD PATIENTS 3pm WT Minimal Shifting Effect for Midday Light Evening / Early Night Light Phase Delay (move later) 3am BT 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) 11am WT 3pm WT Associated Professional Sleep Societies, LLC 47
Gradisar et al., Sleep, 2011 DSPD RCT: CBT + PHOTOTHERPY Age 11-18, DSPD diagnosis CBT (n=23) sleep education (Session 1) heavy cognitive component (Sessions 2-5) Wrap-up (Session 6) 30-120 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 Associated Professional Sleep Societies, LLC 48
Gradisar et al., Sleep, 2011 DSPD RESULTS 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 Associated Professional Sleep Societies, LLC 49
DSPD MELATONIN phase shifting Max phase advance: give 5 hr prior to DLMO 1 DLMO is ~1.5 to 2 hr. prior to BT 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 Associated Professional Sleep Societies, LLC 50
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 9pm 12am MELATONIN [indicated: guideline] BASELINE / STABILIZATION 1. 30min. ADVANCE OF BT/WT SCHEDULE PER DAY 2. MELATONIN 15-30min. PRIOR TO BT 3. 2hr DIM LIGHT PRIOR TO BT 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 Wyatt, 2008 Associated Professional Sleep Societies, LLC 51
DSPD MELATONIN FOR DSPD Meta-analysis of 9 suitable studies 0.3-5 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 Associated Professional Sleep Societies, LLC 52
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 Associated Professional Sleep Societies, LLC 53
DSPD DSPD: PHOTOTHERAPY + MELATONIN 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 Associated Professional Sleep Societies, LLC 54
SHIFT WORK Nap during night or extended shifts [indicated: standard] Hypnotic for day sleep [indicated: guideline] Recovery sleep rebound sleep, telephone & doorbell off, protected sleep time (kids, pets) catch up prior to next night shift Error detection systems, redundancy Light exposure at work for stimulatory effect Don t work shifts some individuals are more intolerant of shift work Associated Professional Sleep Societies, LLC 55
THE END Associated Professional Sleep Societies, LLC 56