Updates in Adult Sleep Medicine 44 th Annual Advances in Internal - PowerPoint PPT Presentation

6/24/2016 Faculty Disclosures No relevant commercial interests Updates in Adult Sleep Medicine 44 th Annual Advances in Internal Medicine Bernie Y. Sunwoo, MBBS Assistant Professor of Clinical Medicine Division of Pulmonary, Allergy, Critical Care and Sleep Medicine Outline Insomnia • Insomnia AASM ICSD-3 definition: • Circadian rhythm sleep-wake disorders 1) Persistent sleep difficulty - Sleep initiation • Sleep disordered breathing - Sleep maintenance - Waking earlier than desired - Obstructive sleep apnea 2) Adequate opportunity and circumstances for sleep - Obesity hypoventilation disorder 3) Associated daytime impairment - Central sleep apnea - Fatigue or malaise; Impaired attention, concentration or memory; Impaired • Sleep related movement disorders social, family, occupational or academic performance; Mood disturbance or irritability; Daytime sleepiness; Behavioral problems; Reduced motivation, • Parasomnias energy, initiative; Proneness for errors, accidents; Concerns about or dissatisfaction with sleep • Hypersomnolence of central origin AASM. International Classification of Sleep Disorders 3 rd Edition 2014. 1

6/24/2016 Insomnia simplified The Scope of Chronic Insomnia • Prevalence varies with the definitions use but you WILL see it – ICSD 2 nd Edition ICSD 3 rd Edition - 10% • Primary • Short-term insomnia disorder - Symptoms approximately 35% - Psychophysiological - <3 months • Chronic insomnia disorder ->3 - Idiopathic • Risk factors - Inadequate sleep hygiene times per week, >3 months - Female sex - ? Increasing age • Other insomnia disorder - Paradoxical - Genetic - Lower socioeconomic status - Medical illness - Psychiatric disorders • Secondary - Substance abuse - Stress - Shift work - Personality • A comorbid disease – sleep, medical, psychiatric disorders, medications and substance use Ohayon MM et al. Sleep Med 2009; 10(9): 952-60 Ohayon MM. Sleep Med Rev 2002; 6:97-111 AASM. International Classification of Sleep Disorders 3 rd Edition 2014 . Buysse et al. Primary Psychiatry 2005; 12(8):50-57 Sleep & Psychiatric disorders Chronic insomnia evaluation A clinical diagnosis • Detailed history – Sleep Psychiatric disorders - Sleep – primary complaint, onset, time course, pre-sleep conditions, sleep-wake schedule, nocturnal symptoms, daytime function, • Almost 1/3-1/2 of individuals with complaints of insomnia or daytime activities hypersomnia have a psychiatric disorder - Medical • ~80% of patients with a depressive episodes describe insomnia - Psychiatric - Sleep complaints are part of the diagnostic criteria of many psychiatric - Medications, substance use disorders • A sleep study is not indicated unless concerns for other sleep disorders 2

6/24/2016 Management What is CBT-I? • Treatment is directed at both the insomnia and the comorbidities • Cognitive therapy – Standard • Cognitive and behavioral therapy for insomnia (CBT-I) Changing beliefs and attitude about insomnia • Behavioral therapy - Effective - as effective or better than pharmacotherapy � ACP recommendation: First line therapy for insomnia - Stimulus control therapy Standard - Major barrier is availability and access, “eCBT-I”. Eg. SHUT i (www.shuti.me) - Sleep restriction therapy Standard • Pharmacologic treatments - Relaxation therapy Guideline • Combination therapy - Biofeedback Guideline - CBT-I and pharmacotherapy, followed by CBT-I alone, shown to produce - Paradoxical intention Guideline better long-term outcomes than either alone - Sleep hygiene education No recommendation Qaseem A et al. Ann Intern Med 2016; 165 - Can facilitate withdrawal of hypnotic agents Wilt TJ et al. Ann Intern Med 2016 Typically 6-8 individual sessions Schutte-Rodin S et al. J Clin Sleep Med 2008; 4(5):487-504 Morin CM et al. Sleep 2007; 30:1547-1554 Morin CM et al. JAMA 2009; 301:2005 Question 1 Good sleep hygiene A 60 year old male, with a history of alcohol dependence and benign No evidence that sleep hygiene education alone is effective for insomnia prostate hypertrophy complains of chronic insomnia. A sleep study did not reveal sleep disordered breathing. Cognitive behavioral therapy for � Use of bed only for sleep insomnia is suggested. Which is the most appropriate medication for treatment of his insomnia? � Maintain regular waking times 54% � Limited caffeine consumption until noon A. Doxepin 25 mg � Quiet, dark and cool environment in the bedroom B. Zolpidem 5 mg � Avoidance of stimulating activity near bedtime C. Diphenhydramine 25 mg � No exercise within 2 hours of bedtime 17% 17% 13% D. Trazodone 50 mg � Face of alarm clock should not be visible from bed � Avoidance of napping if sleep maintenance is a problem 3

6/24/2016 Pharmacologic treatments Which drug ? • Agents • ACP recommendation: Use a shared decision-making approach, - Benzodiazepine-receptor agonists including a discussion of the benefits, harms and costs of short-term - Antidepressants use of medications, to decide whether to add pharmacological - Orexin antagonists therapy in adults with chronic insomnia disorder in whom CBT-I alone - Melatonin agonists is unsuccessful • Little data comparing the effectiveness of different medications - Others • Choice depends on: • Little long term efficacy data - Nature of insomnia & duration of medication action - Medications should ideally be used for no longer than 4-5 weeks - Co-morbidities - Drug interactions - Prior treatment failure and side effects - Cost Wilt TJ et al. Ann Intern Med 2016 Benzodiazepine receptor agonists Sedating antidepressants & antipsychotics • Shown to decrease sleep latency (10 mins) and depending on duration of action, • Relatively little evidence on effectiveness in patients without potentially increase total sleep time and decrease WASO depression • Lower doses than doses used for antidepressant effects Benzodiazepine Nonbenzodiazepine BZRA • • • Commonly used agents Decrease stage N3 sleep Less anxiolytic, myorelaxant and anticonvulsant activity • Less rebound, respiratory depression or evidence of tolerance - Trazodone (25-100 mg) - Triazolam (Halcion) [S] - Zaleplon (Sonata) [S] - Very modest efficacy in patients with depression - Side effects – postural hypotension, priapism - Estazolam (Prosom) [S] - Zolpidem IR (Ambien, Intermezzo, Zolpimist, Edular) [S-I] - Mirtazapine (7.5-15 mg) - Temazepam (Restoril) [I] - Zolpidem CR [I] - Side effects – weight gain - Alprazolam (Xanax) [L] - Eszopiclone (Lunesta) [I] - Quetiapine (12.5-50 mg) - Lorazepam (Ativan) [L] - Side effects – QT prolongation, weight gain, extrapyramidal side effects, headaches, lens changes, leukopenia - Flurazepam (Dalmane) [L] - Doxepin (1-6 mg) - Shown to decrease wake after sleep onset time • Side effects – sedation, anterograde amnesia, tolerance, dependence, rebound - Only FDA approved antidepressant for the treatment of insomnia - Side effects - anticholinergic insomnia, fall risk, sleep behaviors, respiratory depression, dementia (HR 2.34) - Amitriptyline (10-25 mg) - Side effects - anticholinergic 4

6/24/2016 Melatonin and MT receptor agonist Orexin antagonists • Melatonin • Orexin A and B are neuropeptides that play a key role in regulating - Hormone produced by the pineal gland during the dark cycle that can decrease the the sleep-wake cycle & promoting wakefulness suprachiasmatic nucleus (SCN) alerting signal • Suvorexant (Belsomra ) is a dual orexin receptor antagonist - ACP insufficient evidence on global and sleep outcomes - Ferracioli-Oda E et al. 2013 meta-analysis suggesting small effect on sleep latency, TST and • Subjective improvements in sleep latency and total sleep time sleep quality - Can cause a phase shift of circadian rhythms • FDA approved in 2014 as a scheduled C-IV controlled substance, maximum dose 20 mg • Ramelteon • Side effects – somnolence, headache, amnesia, abnormal dreams, - MT1/MT2 receptor agonist and x17 times more potent then melatonin emergence of narcolepsy symptoms, dry mouth, sleep walking, RBD, - Short acting and few studies suggesting small reduction in sleep latency. Approved in the US for sleep onset insomnia suicidal ideation, CYP 3A4 metabolism, rebound insomnia, worsening - Lacks abuse potential depression - Side effects – headache, nausea, dizziness, somnolence, nightmares, hallucinations, rarely suicidal ideation, contraindicated in patients taking fluvoxamine Ferracioli-Oda E et al. PLoS ONE 8(5) Kuriyama A et al. Sleep Med 2014; 15:385 Kishi T et al. PLosOne 2015; 10(8) Michelson D et al. Lancet Neurol 2014; 13:461 Wilt JJ et al. Ann Intern Med 2016 Wade AG et al. Curr Med Res Opin. 2011; 27:87-98 Wilt T J. Ann Intern Med 2016 Over the counter medications Question 2 A 23 year old male complains of difficulty falling asleep and inability to • Most are diphenhydramine, a sedating antihistamine wake up for his classes in the morning. On weekdays he is unable to fall • Limited evidence exists for efficacy asleep until 2 AM. He wakes at 6 AM using an alarm and is drinking up to • Side effects 6 cups of coffee in the mornings to try and stay awake. On weekends he wakes at 11 AM and feels refreshed. He denies snoring. What is the most 54% likely cause for his insomnia ? 46% A. Obstructive sleep apnea B. Restless legs syndrome C. Poor sleep hygiene 0% 0% D. Delayed sleep wake phase disorder 5