Sleep Disorders Medicine: Ottawa Review Course PDF

Sleep Disorders Medicine: Ottawa Review Course Elliott Kyung Lee MD, FRCP(C), D. ABSM, Sleep Specialist Medical Director, Sleep Disorders Clinic Royal Ottawa Mental Health Center Associate Professor, Dept of Psychiatry, UOttawa Ottawa Review Course January 6, 2025 PRESENTER DISCLOSURE Presente...

Sleep Disorders Medicine: Ottawa Review Course Elliott Kyung Lee MD, FRCP(C), D. ABSM, Sleep Specialist Medical Director, Sleep Disorders Clinic Royal Ottawa Mental Health Center Associate Professor, Dept of Psychiatry, UOttawa Ottawa Review Course January 6, 2025 PRESENTER DISCLOSURE Presenter: Elliott K. Lee MD, FRCPC, D. ABSM, F. APA, F. AASM Relationships with commercial interests: none Contract work with CADTH (Canada Drug and Health Technology Agency) Some slide graphics provided by Eisai medical, modified by Elliott Lee Royal College Examiner LEARNING OBJECTIVES 1) Describe the stages of sleep and normal homeostatic and circadian influences. 2) Describe polysomnography including the electrical and physiologic variables monitored and illustrate its clinical utility in psychiatry 3) Discuss the epidemiology, clinical features, diagnosis and treatments of breathing related sleep disorders, restless legs syndrome (Willis Ekbom Disease) and periodic limb movement disorder, parasomnias, insomnia, and hypersomnolence disorders. 4) Illustrate the bidirectional relationship of sleep difficulties and psychiatric illnesses including mood disorders, PTSD and (x drug) use disorder. SLEEP ARCHITECTURE STAGES OF SLEEP NREM & REM NREM = N1, N2, N3 N1 and N2 are light sleep Sleep Cycle REM increases as the night progresses Changes across the lifespan  SLEEP HYPNOGRAM Blueprint of what our sleep should look like W N1 N2 N3 REM 1 2 3 4 5 6 7 Hours ***1st half – more SWS; 2nd half, more REM sleep, REM cycles in the night REM length increases throughout the night Average of 3 to 5 REM cycles throughout the night WAKEFULNESS (Alpha – awake, eyes closed) Stage N1 (5%), theta REM (25%) (Paradoxical Sleep) Theta, sawtooth waves Metabolically irregular ?Emotional memory? Stage N3 (20-25%) REM (25%) (Slow Wave Sleep - SWS) (Paradoxical Sleep) Delta Sleep (∆) Theta, sawtooth waves Physically restorative, Metabolically irregular Declarative memory (facts) ?Emotional memory? Most difficult to arouse How can we assess our sleep? Assessment of sleep Sleep history Polysomnography (PSG) - Type/Level I, III most common - Type/Level IV Actigraphy Technologies - wearables, nearables  Sleep-wake history Overview of typical night’s sleep - initiation, maintenance, termination - work vs. vacation, weekends, travel, shifts Nocturnal symptoms - snoring / sleep disordered breathing (SDB) - movements - behaviors (dreams, parasomnias etc.) Daytime symptoms - sleepiness, driving - cataplexy, hypnagogic hallucinations, sleep paralysis Substances – caffeine, nicotine, alcohol, other Silber MH. Continuum (Minneap Minn). 2017; 23(4): 973-88  Measuring Sleep (Polysomnography) EEG – brainwaves Blood oxygen saturation (Central & Occipital Leads) (SaO2) EOG – eye movements Snore microphone EMG – muscle tone –chin, legs Digital AV recording ECG – heart Breathing: 1) Airflow: (nose/mouth) 2) Effort: Thoracic & Abdominal EEG = Electroencephalography EOG = electrooculography EMG = Electromyography ECG = electrocardiography SaO2 = blood oxygen saturation AV = audiovisual  Polysomnography (PSG) - Most comprehensive, objective evaluation of sleep Indications - Suspicion of Breathing related sleep disorder (SDB) Parasomnia (e.g. RBD) Movement disorder (e.g. PLMD) Other (seizure etc.) - Objectively quantify sleep e.g. before MSLT - Titration CPAP, BIPAP - Therapy evaluation Oral appliance, provent etc. SDB = sleep disordered breathing RBD = REM behavior disorder PLMD = periodic limb movement disorder MSLT = multiple sleep latency test CPAP = continuous positive airway pressure BiPAP = Bilevel positive airway pressure Littner MR et al. Sleep. 2005; 28(1): 113-21  Polysomnography (PSG) Type I – Most comprehensive Type II-III (Type III most common) In lab study [attended] “Home sleep study” (HSAT) the most leads! Recommended in uncomplicated adult patients with clinical symptoms suggest higher risk of moderate to severe OSA Type IV – e.g. Overnight Oximetry (OVOX) If single test is negative → Type I PSG is recommended Unattended – 1-2 signals excessive daytime sleepiness Symptoms: EDS + ≥2 of Positive results help rulesleep in SDB disorder breathing habitual loud snoring witnessed apnea/choking Negative results do not r/o SDB hypertension TLDR: if you suspect OSA, can try type 2 ot 3, but if negative, do the most extensive Type 1 HSAT = home sleep apnea test SDB = sleep disordered breathing EDS = excessive daytime sleepiness Kapur VK et al. J Clin Sleep Med. 2017; 13(3): 479-504 TYPE IV data TYPE IV data  Actigraphy Accelerometer – days-wks activity Indications: - Insomnia - CRSWD - Insufficient sleep syndrome Assess - Estimate TST - Prior to MSLT - With Type III (home sleep) tests NOT for assessment of PLMD(movement disorder) Black = moving Blue = computer generated algorithm guess for when the person sleeps CRSWD = circadian rhythm sleep wake disorder TST = total sleep time Smith MT et al. J Clin Sleep Med. 2018; 14(7): 1209-30 MSLT = multiple sleep latency test PLMD = periodic limb movement disorder Sleep Technologies “Wearables” “Nearables” Pillows Mattresses (e.g. Casper, Withings Sleep Tracking Pad, ReST bed etc.) Activity monitors (Fitbit, Jawbone etc.) Apps (1000s+++) Rings (Oura, etc) Challenges: a) Not clear how accurate information is Generally: higher sensitivity (>90%) (classifying sleep) wider specificity (20-80%) (classifying wake) (most data: Fitbit Altra, Fitbit Versa, WHOOP, Oura) b) Not clear whether such information is helpful c) Mostly evaluated in healthy populations (e.g.↑inaccuracy in pts with mental health, sleep disorders) Depner CM et al. SleepJ 2020; 43(2): 1-13 Meltzer LJ et al. Sleep 2015; 38(8): 1323-30 Al Mahmoud A et al. Front Psychiatry 2022; 13: 1-7  Orthosomnia This Photo by Unknown Author is licensed under CC BY https://www.bundabergnow.com/2019/07/27/tech-talk-is-your-smart-phone-ruining-your-sleep/ Seeking treatment for concerns about sleep tracker data related to sleep duration and/or quality Spending excess time in bed for “8 hours sleep/night” Baron KG et al. J Clin Sleep Med 2017; 13(2): 351-4  Sleep Stage % by Age Slide courtesy Dr. Alan Douglass  REM Sleep Rapid Eye Movements Muscle atonia (paralysis) Dream recall 90 minute latency “Paradoxical Sleep” – EEG mimics wakefulness Breathing irregular, heart rate fluctuates What do we need for sleep to be restorative? Sleep Factors Impacting Restoration Sleep Quantity Sleep Quality Sleep Timing NSF recommendations, 2015  Sleep Quantity Too little – equivalent to functioning with 0.05 blood alcohol level ( accuracy2,3 Long term association with cardiovascular disease4 - diabetes, inflammatory markers, sympathetic activity Cogntiive function suffers first with decreased sleep, followed by speed and accuracy 1Williamson AM and Feyer AM. Occup Environ Med 2000; 57; 649-55 2Koslowsky M and Babkoff H. Chronobiol Intl. 1992; 9(2); 132-6 3Reilly T and Edwards B. Physiology and Behaviour. 2007; 90; 274-84 4Faraut B et al. Sleep Med Rev. 2012; 16(2); 137-49 https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/healthy-living/canadian-adults-getting-enough- sleep-infographic/64-03-18-2136-Sleep-Adults-Infographic-EN-Final-03.05.2019.pdf Quality  Timing If timing of sleep not in line with circadian rhythm, quality and quantity will suffer This Photo by Unknown Author is licensed under CC BY-SA https://photo.stackexchange.com/questions/87248/is-out-of-focus-photography-very-niche-or-lost-cause SLEEP CONTROL  Orexin and OxR efferent pathways associated with arousal, vigilance state, and reward pathways. Orexin is neurotransmitter secreted by lateral hypothalamus Orexin high in day to promote wakefulness but silent in night Anthony L. Gotter et al. Pharmacol Rev 2012;64:389-420 © 2012 by The American Society for Pharmacology and Experimental Therapeutics Tsujino, N. and T. Sakurai (2009). Pharmacol Rev 61(2): 162-176. SCN = suprachiasmatic nucleus VLPO = ventrolateral preoptic nucleus  Two processes, Process S and Process C to coordinate sleep Sleep Control Process Process S(leep) C(ircadian) Process S(leep) Accumulate sleep debt throughout the day, and then when we sleep, we pay the debt Homeostatic control “The longer we’re awake, the more sleep debt we accumulate i.e. the sleepier we become” The sleepier we are, the more deficits are seen To date, there is no surrogate available for good quality sleep. Process S(leep) Homeostatic control “The longer we’re awake, the more sleep debt we accumulate i.e. the sleepier we become” The sleepier we are, the more deficits are seen To date, there is no surrogate available for good quality sleep. SLEEP Circadian Rhythms Individual neurons, dissociated in vitro, maintain circadian rhythm, but slightly off (usually longer – 24.2 h) Intrinsic rhythmicity requires daily resynchronization (entrainment) from daily cues (“zeitgebers”) e.g. 1) LIGHT 2) Dark (melatonin) 2) Exercise 3) Food/meals 4) Job 5) Social demands  Light and pineal gland send signals to pacemaker, pacemaker determines cirdcadian rhythm Type text here Suprachiasmatic Nucleus (Melatonin – dark) (“pacemaker”)  Suprachiasmatic nucleus Photoreceptors include melanopsin – sensitive to light – 450-480 nm (blue light) Light exposure in the late evening hours will disrupt/delay sleep (computer, video games etc.) Light exposure ↓ melatonin secretion Asynchronous Sleep Consequences If we do not sleep along with circadian rhthym, this happens! Poor sleep continuity ↓ alertness ↑cognitive errors Mood disturbances “Fishing at wrong time” – sleep is inefficient Jet lag, shift work  Circadian typology when puberty strikes, they need to go to bed later and sleep in. may be best sleeping at midnight and sleeping in until 10 am Delayed at puberty, peak delay at 20 yrs old, then advances with each decade (preserved across mammalian species) Greater delays seen in vs (but earlier onset) Phase tolerance, and responsiveness to zeitgebers ↓with age Social jet lag - chronic misalignment between the preferred sleep- wake schedule and the sleep/wake timing imposed by a person’s social or occupational schedule (most often seen with evening preference) Lee EK. Introduction to Circadian Rhythm Disorders. From Circadian Rhythm Sleep Wake Disorders: An Evidence Based Guide for Clinicians and Investigators. ed R Auger, 2020; p 29-44 Sleep Duration is Dependent on Circadian Timing Asleep at 23:00 h - wakes up after 8 hours Asleep at 0300h - wakes up after 6.5 hours Asleep at 0700h - wakes up after 4.5 hours (difficult to stay asleep when body temperature is misaligned to circadian rhythm) Bjorvatn B and Pallesen S. Sleep Med Rev 2013; 13(1): 47-60  Melatonin Rhythm DLMO Dim Light Melatonin Onset Dim Light Melatonin Onset (DLMO)  Melatonin secretion profiles change with age Karasek, Exp Gerontol, 2004; 39(11-12): 1723-9 Circadian Rhythm Sleep-Wake Disorders (DSM-5) Persistent/recurrent pattern of sleep disruption due to alteration in circadian system or to misalignment of circadian rhythm to sleep wake schedule Disruption leads to excess sleepiness or insomnia Clinically significant distress  Circadian Rhythm Sleep-Wake Disorders Delayed sleep phase type – adolescents/young adults (eg bedtime 1-6 AM; can be familial) Advanced sleep phase type (elderly) (eg bedtime 6-8 PM; can be familial) Irregular sleep-wake type – 3 sleep episodes/24 hr period; elderly, neurocognitive disorder, CNS injury Non-24 hour (e.g. 25 hr clock; Hypernychthemeral syndrome, free running) – especially blind people Shift work type Circadian System Regulation Light Melatonin SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP SLEEP  Melatonin 0.1-0.3 mg produces physiologic levels of melatonin 1.0 mg – produces supraphysiologic levels (e.g. 500-600 pg/mL) Maximum level reached 45 min after administration T½ = 90 min Metabolized cytochrome P4501A2 Many studies suggest timing is more important than dosage for administration Questions about purity/quality are concerning (use products with NPN) Side effects: sedation, GI, nightmares, H/A, irritability Lee EK. Introduction to Circadian Rhythm Disorders. From Circadian Rhythm Sleep Wake Disorders: An Evidence Based Guide for Clinicians and Investigators. ed R Auger, 2020; p 29-44 Erland et al. J Clin Sleep Med 2017;13(2):275-281 NPN = natural product number SLEEP DISORDERS  Sleep Disorders Symptoms Insomnia Excessive Daytime Sleepiness Nocturnal Spells Predisposing, Precipitating, Perpetuating Factors to Insomnia Medical Psychiatric Age Disorders Disorders Behavioural and Primary Sleep Acute and Psychological Circadian Medications Disorders (e.g. Chronic Factors Rhythm and and Sleep Apnea, (e.g. excessive Restless Legs Stressors time in bed) Zeitgebers Substances Syndrome) Increased Arousal Chun S & Lee EK, CGS journal of CME, 2016 INSOMNIA  Excessive Daytime Sleepiness Lack of sleep (Inadequate quantity of sleep) – Insufficient time in bed Inadequate quality of sleep – Sleep Apnea, PLMD, environment Intrinsic sleepiness – Narcolepsy; Idiopathic Hypersomnia Medical/psychiatric disorder – Mood disorder – Medications, medical – thyroid, anemia etc. Circadian Rhythm Disturbance – Shift work, delayed sleep phase, etc. “Nocturnal “Spells” NREM Sleep Arousal Disorder (parasomnia) Night terror type, Sleepwalking type REM Sleep Arousal Disorder (parasomnia) Nightmares, REM behavior disorder etc Seizure Disorder Psychiatric e.g. Panic attack etc.  Sleep Disorders Obstructive Sleep Apnea/hypopnea (OSA) Restless Legs Syndrome (RLS) Periodic Limb Movement Disorder (PLMD) Narcolepsy REM behavior disorder (RBD)  Airway closing during sleep, but frequency of events = more severe OSA Snoring OSA Mild Moderate (AHI 15-30/hr) Severe (AHI >30/hr) (AHI 5-15/hr) (Upper Airway Resistance Syndrome) Type text here Obstructive Sleep Apnea (OSA) hypopneas = 30% reduction in sleep Def’n: Abnormal breathing (apneas/hypopneas) in sleep due to back of throat and tongue relaxing Sleep is disrupted, usually without recall. → Sleep deprivation +/or daytime sleepiness occur Up to 34% of men and 17% of women affected → 90% of patients likely undiagnosed1 50%-76% of snorers are thought to have OSA2, 3 More common in overweight people* -butsignificantly underestimated large proportion are mildly overweight aor regular weight! 1Gottlieb DJ and Punjabi NM. JAMA, 2020; 323(14): 1389-1400 2Young et al. N Eng J Med, 1993; 328(17): 1230-5 3Lugaresi et al. Sleep, 1980; 3(3-4): 221-4 4Kim JW et al. Clin Exp Otorhinolaryngol, 2015; 8(4): 376-80 Epidemiology of OSA Prevalence – up to 22% , and 17% , all ages1 / = 2:1, until menopause, then 1:1 50% of snorers have OSA2 80% , 93% with moderate/severe OSA, undiagnosed3 Key diagnostic questions: - Do you feel satisfied with the quality of your sleep? - Does your partner complain that you snore? - (STOPBANG) 1Franklinet al. J Thorac Dis, 2015; 7: 1311-22 2Lugaresi et al. Sleep, 1980; 3(3-4): 221-4 3Young et al. Sleep, 1997; 20: 705-6  STOP BANG – screening for OSA ≥2/4 in STOP, or ≥3/4 of STOP BANG has high sensitivity for obstructive sleep apnea Do you SNORE? Are you TIRED in the day? Any OBSERVED apneas? Do you have high blood PRESSURE? BMI > 35 kg/m2 Age>50 NECK circumference over 40 cm? GENDER – Male ≥3/4 - Sensitivity 88% for mild OSA, increases with increasing severity STOP – 65% sensitivity for AHI >5; 75% for AHI > 15; 80% for AHI > 30 BANG – body mass index >35 kg/m2, Age > 50 , neck circumference >40 cm, Gender – male With STOPBANG together, >3 points= AHI> 5, 83%, AHI>15, - 93%, AHI>30 = 100% sensitivity Chung F et al. Anesthesiology 2008; 108: 812-21. Chiu HY et al. Sleep Med Rev 2017 (36); 57-70 Global Heat Map of OSA Prevalence >4 700 000 (!) *(Age 30-69) Benjafield AV et al. Lancet Respir Med, 2019; 7 (8): 687-98  OSA diagnosis is important, as associated with the following: Other Diseases and OSA Hypertension***New England Journal of Medicine 2000; 342:1378-84 Atherosclerosis Circ Res 2000; 87:840-4 Atrial fibrillation/CHF Chest 2000; 118:591-5 Stroke Neurology 2002;58:911-916, Sleep 2003;26:293-297 Impaired Glucose Control J Intern Med 2003:32-44 Gastroesophageal reflux disease Am J Med:2003; 115:109s-113S Major depressive disorder Chest, September 2005; 128: 1304-1309. ADHD Neurocognitive dysfunction Sleep, Arousal, and Performance 1992:177-88  TREATMENTS FOR OSA **CPAP – Continuous Positive Airway Pressure **Weight Loss - ↓ BMI = ↓ RDI Avoid Alcohol, Sedatives (increase muscle relaxation) “Snoreball” Technique / Positional Therapy Oral appliance therapy (OAT)/ Mandibular repositioning device Provent/Bongo Bongo = replacement for Provent, can reuse for 3 months Provent (no longer avaialble) = EPAP, adheres to nostril and using microvalves, uses breathing to create pressure in airways eXciteOSA = daytime therapy for OSA! Upper Airway Surgery – Tonsillectomy (pediatrics) – Uvulopalatopharyngoplasty (UPPP) – Inspire Therapy = only available is US, implanted device that stimulates muscles in the airway to stay open based on your needs – Maxillomandibular Advancement (MMA) – Tracheostomy  Sleep apnea is worst in REM sleep! OSA and Mental Illness OSA can exacerbate mental illness: - Aggression/cognition in schizophrenia - Mood disorders (MDD, bipolar) - Nightmares in PTSD - Cognitive dysfunction in neurocognitive disorders - Relapse to substance abuse - ADHD OSA and MH issues have bidirectional relationship - both worsen the other and vice versa Lee EK and Douglass AB. Can J Psychiatry, 2010; 55(7): 403-12  Prevalence of OSA in SMI (serious mental illness) Metaanalysis and systematic review: 570 712 participants (Stubbs B et al) Objectively assessed for OSA (AHI>5) Overall prevalence of OSA in SMI: 25.7% - Major depressive disorder: 36.3% - Bipolar disorder: 24.5% - Schizophrenia: 15.4% Older age and increasing BMI predicted OSA PTSD, Neurocognitive disorders also highlighted with high frequency of OSA in other studies Stubbs, B., et al (2016). J Affect Disord 197: 259-267. Gupta MA and Simpson FC. (2015). J Clin Sleep Med; 11(2): 165-75 Oliver, C., et al (2024). Sleep Med Rev 73: 101869. Obstructive sleep apnea Approximately 1/5 pts with OSA may have a depressive disorder Approximately 1/5 pts with a depressive disorder may have OSA Pts with Depressive disorder- 5X more likely to have OSA than non depressed patients Ohayon MM et al. J Clin Psychiatry. 2003; 64: 1195-1200  Sleep Deprivation and Children Not the same as adults ADHD Crowd May be “hyperactive” - fidget - poor attention - cranky Undx’d OSA may be mistaken for or exacerbate ADHD in 20-50% of ADHD pts Youssef, N. A., et al. (2011). Ann Clin Psychiatry 23(3): 213-224. Miano, S., et al. (2019). Sleep Med 60: 123-131. Urbano, G. L., et al. (2021). Children (Basel) 8(9).  Periodic Limb Movements (PLMs) & Restless Legs Syndrome (RLS) Picture courtesy FOAMed  Periodic Limb Movements (PLMs) Repetitive leg (limb) movements DURING SLEEP Typically 20-40 seconds apart Cause awakenings and fragmentation Patient often unaware. Bedpartner reports “kicking” c/o frequent awakenings, light sleep aka Nocturnal Myoclonus  Restless Legs Syndrome – DSM-5 “URGE” Unpleasant sensation U – rge to move legs R – est – symptoms worsened at rest G – ets better with movement E – vening – symptoms worse in evening ◼ ≥ 3x/week, ≥ 3months ◼ Significant distress ◼ Not due to medical condition, substance  Epidemiology/Pathology – RLS/PLMD 5-10% of the population affected ( / =2/1) Dopamine dysfunction (receptor?) Involves a circadian fluctuations in dopamine Deficiencies - especially iron, play a role. Key diagnostic question: Do your legs ever bother you at night? Allen RP et al. Sleep Medicine (4). 2003: 101-19  RLS and Psychiatric Comorbidity Winkelman and Colleagues- 238 pts with RLS – evaluated for psychiatric disorders vs controls (12 m prevalence): OR Panic Disorder 4.65 Generalized Anxiety Disorder 3.52 Major Depressive Disorder 2.55 Winkelman et al. J. Neurol (2005) 252 : 67–71 RLS/PLMD TREATMENT  Address Exacerbating Factors Caffeine Tobacco Alcohol Medications - dopamine blockers (5HT2A/D2 antag, GI motility agents) - antidepressants (SSRIs, SNRIs) - mirtazapine* - lithium *Fulda S et al. Sleep 2013;36:661-9  Exacerbating Influence of Psychotropics on RLS/PLMS D2, 5HT2A/D2 antagonists 1,2 Lithium3,4 SSRIs, SNRIs (PLMS)5,6 – Consider bupropion7,8 1. Horiguchi J, et al. Int Clin Psychopharmacol. 1999;14:33. 2. Kraus T, et al. J Clin Psychopharmacol. 1999;19:478. 3. Heiman EM, Christie M. Am J Psychiatry. 1986;143:1191. 4. Terao T, et al. Biol Psychiatry. 1991;30:1167. 5. Brown LK, et al. Sleep Med. 2005;6:443-450. 6. Yang C, et al. Biol Psychiatry. 2005;58:510. 7. Kim S, et al. Clin Neuropharmacol. 2005; 28:298. 8. Nofzinger EA, et al. J Clin Psychiatry. 2000;61:858. Slide courtesy Dr. Robert Auger, modified by Elliott Lee  Check Iron (Ferritin)! Absorption - GI difficulties (e.g. surgeries?) Blood loss / iron absorption / intake? - Anemia – Cough? Poop? - Menstrual Periods/Pregnancy - Blood donations - Diet (vegetarian, vegan) - Medications (e.g. proton pump inhibitors) Start iron if ferritin < 75 μg/L or transferrin saturation < 20% (Also supplement if Vit B12 (65 yrs old (Health Canada) Eszopiclone (Lunesta) 1-3 6 Max 2 mg >65 yrs old (Health Canada) Sleep induction within 15-30 min Beers criteria (2023): Strongly suggests Z drugs to be avoided in older adults Chun, S. and Lee EK (2016). Canadian Geriatric Society Journal of CME 6(1). https://www2.gov.bc.ca/assets/gov/health/practitioner-pro/provincial-academic-detailing-service/pad_insomnia_handout.pdf American Geriatrics Society Beers Criteria Update Expert, P. (2023). "American Geriatrics Society 2023 updated AGS Beers Criteria(R) for potentially inappropriate medication use in older adults. J Am Geriatr Soc 71(7): 2052-2081. Huedo-Medina, T. B., et al. (2012). BMJ 345: e8343.  Benzodiazepines Sleep induction within 30 min Adverse consequences: fall risk, MVAs, daytime sedation, anterograde amnesia, rebound insomnia, dependence BDZ use →dev of neurocognitive disorders? (mixed results; neuroprotective?) Beers criteria (2023): Strongly suggest avoiding chronic BDZ use in older adults Osler, M. and M. B. Jorgensen (2020). Am J Psychiatry 177(6): 497-505. Salzman, C. (2020). Am J Psychiatry 177(6): 476-478. Nafti, M., et al. (2020). Ann Pharmacother 54(3): 219-225. American Geriatrics Society Beers Criteria Update Expert, P. (2023). "American Geriatrics Society 2023 updated AGS Beers Criteria(R) for potentially inappropriate medication use in older adults." J Am Geriatr Soc 71(7): 2052-2081. Take home messages… Z-drugs and BDZs helpful for sleep initiation/maintenance (short term use) Z-drugs may have less side effects due to selective actions on GABA-A receptor, but lose selectivity at higher doses Risks - dependence, falls, daytime impairment, ?memory Z-drugs, BDZs not recommended for older adults (chronic) Zolpidem ? for sleep initiation Zopiclone/eszopiclone ?sleep initiation + maintenance, (daytime side effects a concern) SEDATING ANTIDEPRESSANTS  Sedating Antidepressants Trazodone*: Limited data on efficacy - helpful comorbid depression, PTSD, medical issues - downregulates physiologic (HPA) arousal) Mirtazapine: Insomnia major depressive disorder, anxiety disorders (caution restless legs syndrome) Doxepin: - Significant antihistamine action (at low dose) - Anti-ach at higher doses 2023 Beers Criteria – avoid >6 mg/day doxepin (as this is when anticholinergic effect comes in) Jaffer, K. Y., et al (2017). "Trazodone for Insomnia: A Systematic Review." Innov Clin Neurosci 14(7-8): 24-34. Chun, S. and E. K. Lee (2016). Canadian Geriatric Society Journal of CME 6(1). American Geriatrics Society Beers Criteria Update Expert, P. (2023). "American Geriatrics Society 2023 updated AGS Beers Criteria(R) for potentially inappropriate medication use in older adults." J Am Geriatr Soc 71(7): 2052-2081.  Receptor Occupancy - Drugs Stahl, S. M. (2008). CNS Spectr 13(12): 1027-1038.  Selective H1 Antagonism Doxepin (1-6 mg) Mirtazapine (2-4 mg) Helpful for Wake After Sleep Onset (WASO) (may not prevent awakenings but return to sleep faster) No change in arousal threshold No cognitive effect, motor impairment Krystal, A. D., et al. (2010). Sleep 33(11): 1553-1561. Krystal, A. D., et al. (2011). Sleep 34(10): 1433-1442. Krystal, A. D., et al. (2013). Sleep Med Rev 17(4): 263-272.  Doxepin side effect profile Side effects Placebo Doxepin Doxepin Placebo Doxepin (3 mg) (6 mg) (3 mg) Overall 27% 35% 32% 52% 38% Headache 10% 5% 0% 14% 6% Sedation 5% 9% 8% 5% 3% Memory 0% 0% 0% 1% 0% Dizziness 1% 0% 0% 2% 2% 5 weeks 12 weeks (adults) (older adults) Krystal, A. D., et al. (2010). Sleep 33(11): 1553-1561. Krystal, A. D., et al. (2011). Sleep 34(10): 1433-1442.  Trazodone for Insomnia Disorder (4 hrs/night, >5 nights/wk Lee EK, et al. In Elsevier Reference Collection in Neuroscience and Biobehavioral Psychology. ScienceDirect; May 2022  Oral Appliance Therapy (Mandibular Repositioning Devices (MRDs) https://ca.exciteosa.com/ Uvulopalatopharyngoplasty (UPPP)