Sleep Medicine

Content In this Page:  Insomnia Shift worker sleep disorder Sleep Apnea  Restless leg syndrome  Narcolepsy  SLEEP DISORDERS (ICSD 3 divides it into 7 major class) INSOMNIA:  Short-term or Acute Insomnia (<3 month): due to stressors (acute pain, grief) Long-term Insomnia:  Other Insomnia:  DDx (6 other major class of sleep disorders): Annals 2014 Sleep-Related Breathing Disorders (OSA, Central Sleep Apnea) Central Disorders of Hypersomnolence Circadian Rhythm Sleep-Wake Disorders (Time Zone Change Syndrome, Shift work sleep disorder, Delayed Sleep Phase, Advanced Sleep Phase) Parasomnias (related to NREM) Sleep Related Movement Disorder (RLS, PLMD, Nocturnal Cramps) Others Diagnosis: Short Term vs Chronic vs Other (All 3 features most be present)  Sleep related complaint (initiating sleep, maintaing sleep, early morning awakening, non-restorative sleep) Such complaint occurs despite adequate opportunities to sleep It produces daytime distress or deficits Insomnia NJEM 2015 Treatment:  Cognitive Behavioral Therapy Sleep hygiene: Ten basic rules for a good night's sleep Up-to-date Stimulus control therapy rules Up-to-date Insomnia NJEM 2015 Medications : 5 major categories  BZD: BZD (Estazolam, Flurazepam, Quazepam, Temazepam, Triazolam) Non-BZD sedatives (Eszopiclone, Zopicolone, Zaleplon, Zolpidem) Anti-depressants (Amitriptyline, Doxepin, Mirtrazapine, Trazodone) Orexin antagonists (suvorexent)  Melatonin agonists (Ramelteon, Melatonin, Prolonged Release) Anticonvulsants - Clonazepam, Gabapentin;  Other: Anti-psychotics - Olanzapine, Quetiapine Insomnia NJEM 2015 Duration of action (see above Chart):  Sonata (s = short acting), < Ambien < Lunesta (l = long acting) < Tenazepam  Sleep onset insomnia : Short Acting (Triazolam, Zaleplon or Sonata, Zolpidem) Reduce sleep latency Sleep maintenance insomnia: longer acting medications - Zolpidem extended release, eszipiclone or Lunesta or ultra-short acting (Zaleplon or Sonata) Longer acting formulations have hangover lasting into the day, but ultra-short acting formulation does not have this concern OTC agent:  Anti-histaminics (Unisom, Aldex AN, Benadryl) Diphenhydramine Doxylamine succinate Note: Even though they are used, they should be avoided due to adverse effects and lack of data on its efficacy  Melatonin agonists (Ramelteon, Melatonin, Prolonged Release) Improves sleep onset, duration, quality. Also, improves REM sleep (Ref:Chapter 64 13e) . However, per Lancet 2012 efficacy is inconclusive and reduces sleep latency by only 7.2 min. Some positive evidence is for delayed sleep phase, and shift work sleep disorder Melatonin: Effective in patients with Insomnia due to Beta Blockers. 0.3–10 mg of the immediate-release formulation given orally once nightly lowest effective dose should be used first and may be repeated in 30 minutes up to a maximum of 10–20 mg sustained released formulation are effective but inferior to immediate release formulation  Ramelteon Minimal side effects, no abuse concern Hypnotic Agents: BZD (Estazolam, Flurazepam, Quazepam, Temazepam, Triazolam) Non-BZD sedatives : Eszopiclone, Zopicolone, Zaleplon, Zolpidem (ambien) Eszopiclone (Lunesta) Improves insomnia when given with SSRI with Fluoxetine for MDD with Escitalopram for GAD  Anti-depressants (Amitriptyline, Doxepin, Mirtrazapine, Trazodone) Others (Anticonvulsants - Clonazepam, Gabapentin; Anti-psychotics - Olanzapine, Quetiapine) Ref Insomnia In the Clinic Annals 2014 Chronic Insomnia Lancet 2012 Up-to-date Basic & Clinical Pharmacology, Chapter 64 13e  SHIFT WORKER SLEEP DISORDER  Pharmacological Interventions for Sleepiness and Sleep Disturbances Caused by Shift Work JAMA 2015 SLEEP APNEA Few Terms: BMJ 2014 Apnea:  cessation, or near cessation of airflow. Airflow reduced to less than 10% (90 % or more reduction) of baseline for more than 10 s; obstructive if respiratory effort is present  (due to complete pharyngeal collapse), central if no respiratory effort is present (no obstruction is present) Lancet 2014 Hypopnea: reduction of airflow but does not meet the criteria of apnea definition. Airflow decreases at least 30% of baseline for more than 10 s, in association with a 4% (3% by new definition) oxygen desaturation (due to partial pharyngeal collapse) Lancet 2014 Apnea / Hypopnea Index (AHI): Number of respiratory events /hr Definition of OSAS:  BMJ 2014 AHI > 5 with associated symptoms of sleep fragmentation  Typically, AHI > 5 is associated with symptoms of excessive symptoms of daytime sleepiness. Hence, cutoff of AHI > 5 is used.  Daytimes Symptoms of Sleep Fragmentation:  Sleepiness, Fatigue, Poor Concentration Signs of sleep fragmentation: Snoring, restlessness, or resuscitative snorts Pathogenesis: BMJ 2014 Anatomy of OSAS Loss of phyrangeal dilator muscle tone (causes airway narrowing) Retropositioning of the Mandible  Narrowing of the lateral phyrangeal wall by fat pads  Neurohormonal Changes of OSAS Autonomic activation to airway obstruction reestablishes the tone and terminates obstruction Sleep related changes Patient with OSAS spend less time in REM (Rapid Eye Movement) Sleep and Restorative Slow wave sleep  Indications for a referral for a sleep study BMJ 2014 Symptoms of excessive sleepiness or an Epworth sleepiness score of ≥11* Recurrent witnessed apneas  Nocturnal choking, gasping, or “dyspnoea” Headache in the morning Unrefreshing sleep despite adequate sleep time and continuity Near miss events or incidents caused by reduced vigilance while driving* Screening before bariatric surgery or upper airway surgery for snoring Otherwise unexplained polycythaemia, pulmonary hypertension, or ventilatory failure Note: Urgent referral is necessary if the Epworth sleepiness score is >18 or the patient has had a road traffic incident or near miss event  Screening Tests for Sleep Apnea: ESS STOP-Bang Tests for OSAS Overnight oximetry  Overnight polysomnography (monitors following 6 areas) Monitoring of Sleep-Wake State EEG (sleep stages)  N3, REM is often absent or reduced in OSA Wake, N1, N2 often increased in OSA   L and R electrooculogram  Chin electromyogram Respiratory effort measurement respiratory inductance plethysmography bands placed around the thorax and abdomen Airflow monitoring nasal air pressure thermal air sensor arterial Oxygen saturation Limb movement assessment EMG of anterior tibialis Body position EKG Severity Mild OSA: 5-15 AHI Moderate OSA: 15 - 30 AHI Severe OSA: > 30 AHI References: Diagnosis of OSA in Adults: A Clinical Practice Guideline From the ACP Annals 2014 Obstructive sleep apnea BMJ 2014 Adult obstructive sleep apnea Lancet 2014 RESTLESS LEG SYNDROME: Primary (or Idiopathic; 40% have family history ) vs. Secondary (Iron deficiency, ESRD, DM, MS, PD, Pregnancy, Rheumatic Disease, Venous Insufficiency, Drugs  PLMD (Periodic Leg Movement Disorder; PLMS - Sleep; PLMW - Wakefulness) may be associated but are not RLS and do not require treatment Dx: URGE Uncomfortable urge to move legs Rest occurrence / worsening Getting up releives Evening Predominance DDx: Peripheral Neuropathy, Lumbosacral radiculopathy, Nucturnal Leg Cramps. Need to differentiate from Akathisia (generalized inner restlessness) Treatment: Dopaminergic agonists (S.E: N, Dizziness, ICD) Augmentation: Tolerance, Overall worse symptoms, Spread to UE, Need of drug earlier in the day; can be treated with alpha-3-delta drugs (gabapentin / pregablin) or an opiate is usually necessary References Drugs that can be associated with symptoms of restless legs syndrome (RLS) Up-to-date Diagnostic criteria for restless legs syndrome / Willis-Ekbom disease Up-to-date Narcolepsy     Narcolepsy NEJM 2015 Narcolepsy NEJM 2015 Narcolepsy NEJM 2015 Narcolepsy NEJM 2015