OUTLINE SLEEP UPDATE 2011 DISCLOSURES. David Claman, MD. Formerly on Lunesta Speakers Bureau Resigned 2011

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1 SLEEP UPDATE 2011 David Claman, MD Professor of Medicine UCSF Sleep Disorders Center DISCLOSURES Formerly on Lunesta Speakers Bureau Resigned 2011 Former Consultant for Provent Consulting activity was in OUTLINE Sleep deprivation is common! Less than 6 hours per night magnifies symptoms Insomnia is also common Up to 25% of population reports occasional insomnia 10% report chronic insomnia Restless Legs Syndrome (2.5-15% prevalence) Obstructive Sleep Apnea Prevalence of OSA syndrome: 2-4% Prevalence of sleep-disordered breathing: 9-24% Is this your air traffic controller, or your postcall resident? 1

2 SLEEP DURATION AND MORTALITY: U SHAPED CURVE (Chien K et al. SLEEP 2010;33(2): ; n=3430; mean age 55) Best survival with 7-8 hours of sleep per night. Worse survival with 6 or 9-10 hours. No causality established. See detailed review in Cappuccio FP. SLEEP 2010;33(5): TAKING A SLEEP HISTORY Senthilvel E et al. J Clin Sleep Med 2011;7(1)41-48 Prospective study of 101 new primary care pts; after appt: subjects answered sleep questionnaires and charts were reviewed for sleep history Berlin sleep questionnaire (validated PPV 0.89) 10 questions on snoring, apnea, fatigue, hypertension Epworth sleepiness scale (ESS) 8 questions on tendency to fall asleep STOP (from Anesthesia) 4 questions: Snoring, Tired, Observed Apnea, Pressure(HTN) STOPBANG adds BMI, age, neck, gender SLEEP HISTORY (cont) Encounter results: 24% of encounters included brief sleep history 9% documented sleep disorder 2% referred to Sleep; 7% referred to psychiatry Questionnaire results: Epworth 28% were sleepy Berlin 33% & STOP 34% at high risk Conclusion: Sleep symptoms common but are not routinely screened Validated tools are available 2

3 Differential Diagnosis of Insomnia Sleep onset or maintenance? Psychiatric / psychological 20-30% of chronic insomnia patients Medical Drugs (especially caffeine and alcohol) Psychophysiological insomnia Worrying usually worsens insomnia Circadian rhythm issues Jet lag or shift work COGNITIVE BEHAVIORAL THERAPY (CBT) Keep regular bedtime and wake-up time (Sleep Restriction?) Keep bedroom quiet, comfortable, & dark Relaxation technique for min before bed Get regular exercise Don t nap Don t lie in bed feeling worried, anxious, or frustrated Don t lie awake in bed for long periods of time Don t use alcohol, caffeine, or nicotine Turn off TV, cell phones, computers (& pagers!!) HYPNOTICS (no active metabolites) Benzodiazepines (shorter-acting) Triazolam mg half-life 2-5 hrs Temazepam mg half-life 7-14 hrs Benzodiazepine Receptor Agonists Zaleplon (Sonata) 5-10 mg half-life 1-2 hrs Zolpidem (Ambien) 5-10 mg half-life 2-5 hrs Eszopliclone (Lunesta) 1, 2 or 3 mg half-life 6 hrs Zolpidem CR (Ambien CR) 6.25 or 12.5 mg half-life 3-4 hrs Melatonin Receptor Agonist Ramelteon (Rozerem) 8 mg dose; half-life 2-5 hrs Melatonin receptor agonist Takes 7-10 days to take effect OTHER SEDATIVES Benzodiazepines help with anxiety, but all have longer half-life Lorazepam hrs; Alprazolam hrs; Diazepam hrs Sedating anti-depressants Trazadone or Mirtazapine Doxepin (Silenor) 1, 3 or 6 mg Benadryl (Tylenol PM) Consider non-sedating antidepressants to help anxiety Paroxetine mg or Citalopram mg (a.m. or p.m.) 3

4 LEG MOVEMENTS AT NIGHT Hypnic myoclonus (sleep starts) - normal! Restless Legs Syndrome (RLS) Most common symptom is insomnia Clinical Diagnosis Periodic Limb Movements of Sleep (PLMS) Legs most common (rhythmic contractions of anterior tibilias), but arm jerks can occur Diagnosed by sleep study to document that kicking causes EEG arousals TREATMENT OF RLS / PLMS Iron deficiency may worsen RLS If ferritin<50, replace iron to raise ferritin>100 RCT of oral iron X 12 wks reduced RLS symptoms Wang J; Sleep Med 2009 RLS symptoms may worsen on antidepressants Medications: Dopaminergic agents (pramipexole or ropinirole) Clonazepam Gabapentin Opiates 4

5 KEY DEFINITION Apnea-hypopnea index (AHI; aka RDI): the average number of respiratory events per hour of sleep Mild 5-15 Moderate Severe > 30 For Medicare: AHI > 15 qualifies for CPAP; if apnea is in the mild range AHI 5-15, then patient can qualify for CPAP with coexisting sleepiness, HTN, CHF or CVA PREVALENCE OF SLEEP APNEA Wisconsin: 602 working subjects, age 30-60, studied by overnight polysomnography Obstructive sleep apnea defined as both AHI > 5 and hypersomnolence 9% of women had AHI >5; 22% c/o hypersomnolence; yields 2% prevalence 24% of men had AHI >5; 15% c/o hypersomnolence; yields 4% prevalence CLINICAL PREDICTORS OF OSA Sleep Heart Health: male, age, BMI, neck girth, snoring & apnea predict AHI>15 Young T et al. Arch Int Med 2002 Apr 22;162(8): T Young; NEJM 1993;328:

6 OVERLAP SYNDROME Marin JM. AJRCCM 2010(182): Refers to patients who have both COPD & OSA; 3 groups were COPD alone, Overlap on CPAP, & Overlap not on CPAP; >200 per group; age 57; f/u 9 yrs 2. CPAP often effective, but may require Bilevel ± oxygen 3. More likely to have elevated pco 2 and pulmonary HTN 4. Conclusions: 1) Higher mortality if OSA is not treated; 2) also more frequent COPD exacerbations TREATMENT Weight loss 10% weight loss reduces AHI by 25% Avoid alcohol and sedatives near bedtime Postural training Tennis balls effective in selected pts Nasal patency Nasal obstruction may also reduce CPAP effectiveness CPAP Most consistently effective treatment New compliance guidelines document >70% 3 mo CFLEX or BiLevel may help if high pressures are uncomfortable LONGTERM USE OF CPAP Best compliance if AHI >30 & sleepy patient McArdle N et al. AJRCCM 1999;159:

7 Cumulative Percentage of New Fatal (A) & non-fatal (B) Cardiovascular Events JM Marin et al. Lancet Mar 16;365(9464): KEY POINTS: 1. Increased mortality seen if AHI>30 2. CPAP reduced risk HOME TESTING Used in clinical practice for many years Approved by Medicare 2009 May be most helpful if used in conjunction with autocpap Best validated in 2 studies Mulgrew Annals Int Med 2007 highly selected cohort of moderate to severe OSA with sleepiness Berry Sleep 2008 VA cohort of sleepy OSA pts Mandibular Advancement Devices Advancement of mandible Enlarge airway behind tongue, but may also enlarge airway behind palate MANDIBULAR ADVANCEMENT OR TONGUE RETAINER? Crossover study of 39 OSA subjects, measure airway size by MRI with 2 oral appliances Mandibular Advancement Splint (MAS) Tongue Stabilizing Device (TSD) Subset of 18 had sleep study to measure AHI: 12 with MAS had 50% reduction, and 10 ithe TSD had 50% reduction Sutherland K et al. Comparative effects of two oral appliances on upper airway structure in obstructive sleep apnea. SLEEP 2011;34(4):

8 Nasal Expiratory Resistor Microvalves open during inhalation, but close during exhalation to generate positive pressure Data on Nasal Expiratory Resistor Berry RB et al. A novel nasal expiratory positive airway pressure (EPAP) device for the treatment of obstructive sleep apnea: a randomized controlled trial. SLEEP 2011;34(4): Nasal Expiratory Resistor reduced Sleepiness Sleepy subjects (Epworth 10) had greater benefit Berry; SLEEP 2011 GENERAL REFERENCES Behavioral and pharmacological therapies for late-life insomnia. CM Morin et al. JAMA 1999;281:991-9 Cognitive Behavioral Therapy and Pharmacotherapy for Insomnia Jacobs GD; Arch Intern Med 2004;164: No More Sleepless Nights: A Proven Program to Conquer Insomnia; Peter Hauri, PhD Principles and Practice of Sleep Medicine. 4th Edition. Kryger, Roth, & Dement Sleep Disorders. Clinic in Chest Medicine 2003 June; 24(2). Krahn LE, Black JL, Silber MH. Narcolepsy: New Understanding of Irresistible Sleep. Mayo Clin Proc 2001;76: Restless Legs Syndrome Foundation: also has good information about Periodic Limb Movements Restless Legs Syndrome. CJ Earley. NEJM 2003;348(21): The Journal SLEEP is devoted entirely to sleep medicine. 8

9 OSA REFERENCES Principles and Practice of Sleep Medicine. 4th edition 2005 Clinics in Chest Medicine. Sleep Disorders. June 2003;24(2). Peppard PE, Young T, et al. Prospective Study of the Association Between Sleep- Disordered Breathing and Hypertension. NEJM 2000;342: Marin JM et al. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005 Mar 16;365(9464): Kanagala R, Murali NS et al. Obstructive Sleep Apnea and the Recurrence of Atrial Fibrillation. Circulation 2003;107: Yaggi HK, Concato J et al. Obstructive Sleep Apnea as a Risk Factor for Stroke and Death. NEJM 2005;353: Masa JF et al. Alternative Methods of Titrating Continuous Positive Airway Pressure. AJRCCM 2004;170: Ferguson KA, Ono T. Et al. A Randomized Crossover Study of an Oral Appliance vs Nasal-Continuous Airway Pressure in the Treatment of Mild-Moderate OSA. Chest 1996;109: