SLEEP SLEEP ME MEDI DICINE NE UPD UPDATE TE David Claman, MD Director, UCSF Sleep Disorders Center Professor of Medicine
DISCLOSURES • No disclosures • Recommended Reading • “Why We Sleep” by Matthew Walker • References listed in talk • OUTLINE • Sleep Deprivation • Insomnia • Restless Legs Syndrome (RLS) • Obstructive Sleep Apnea (OSA)
SLEEP OVER LIFESPAN • REM sleep is preserved; REM likely involved in memory consolidation • Deep sleep (Delta or N3) is preserved in elderly women but reduced in elderly men • Purpose of sleep is still unknown; likely involves eliminating metabolites that accumulate during wakefulness
Chronic Sleep Deprivation (0 v 4 v 6 v 8 hrs) Lapses in Concentration: 8 hours has fewest! (Van Dongen Sleep 2003) Presently Americans sleep 6 hours 51 minutes on weekdays; 7 hours 37 minutes on weekend (National Sleep Foundation poll: 23 ‐ 60 y/o) Symptoms of sleep deprivation clearly increase if you sleep 6 hours or less
What is your preferred sleep aid for personal use? • A. Zolpidem • B. Melatonin • C. Diphenhydramine • D. CBD • E. Stay up later
DIFFEREN DIFFERENTIAL IAL DI DIAGNO NOSI SIS OF OF IN INSOMNIA IA May be sleep onset, sleep maintenance or early awakening • Psychiatric / psychological • Depression or anxiety • Medical illness – pain, nocturia, post ‐ nasal drip, dyspnea (heart/lungs) • Drugs in general • Caffeine delays sleep onset • Alcohol can cause middle of the night awakenings • Psychophysiological insomnia • Somaticized tension from anxiety causing insomnia • Poor sleep hygiene • Maladaptive coping mechanisms are common • Circadian rhythm issues • Jet lag, Shift work, Advanced or Delayed Sleep Phase
SLEEP SLEEP HY HYGI GIENE ENE GUI GUIDELI ELINES • Keep regular bedtime and wake ‐ up time (even on weekends) • Keep bedroom quiet, comfortable, & dark • Relaxation technique for 10 ‐ 20 min before bed • Get regular exercise • Don ’ t nap ‐ if you have insomnia • OK to nap if you are sleep deprived! • 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 for 3 hours before bed, & caffeine for 8 hours before bed • Paperback self ‐ help book: “ Say Good Night to Insomnia ”
OPTI OPTIONS ONS TO TO TA TAPER HYPNO HYPNOTICS ICS Motivated patients can make progress! Figure 1. 10 week Intervention. Weekly Quantity of Benzodiazepine Medication Used by Older Adults With Insomnia in a Randomized Clinical Trial of Three Interventions to Facilitate Benzodiazepine Discontinuation; 69/76 completed study; 63% drug-free at follow-up; CM Morin. AmJPsych 2004;161:332-342
CB CBTi Ti: Cogn gnitiv itive Beha Behavi vior oral al Ther Therapy fo for In Insom somnia ia Morin CM. JAMA 2009;301:2005 • CBTi includes multiple modalities • Sleep Restriction – less hours in bed • Stimulus Control – only in bed when sleepy • Relaxation – meditation; deep breathing • Cognitive Therapy – individualized • Mindfulness – non ‐ judgmental awareness of moment • Sleep Hygiene – avoid naps, caffeine, alcohol
CBTi improves both insomnia and depression Ashworth DK. J Couns Psychol 2015;62:115 • N=41;Stable on antidepressant for 6 wks • 4 CBT sessions versus self ‐ help reading materials • @3 month f/u: 61% remission of both insomnia and depression in CBTi group versus 5% in self ‐ help
NEUR NEUROTRANSM RANSMITTER ERS –Ar –Arousals usals & Sl Sleep eep Saper, Scammell & Lu (2005) Nature 437:1257 ‐ 63 Sleep Rhythms and Circadian Rhythms both affect sleep
Medications: preferably only if necessary! • Hypnotics are usually best for sleep ‐ onset insomnia; GABA mechanism. These meds have no anti ‐ anxiety benefits. Examples: zolpidem, eszoplicone • Sedatives: Benzodiazepines like lorazepam help with anxiety, but have longer half ‐ life; also GABA mechanism • Sedating antidepressants: trazodone and mirtazapine are longer acting so often used for sleep maintenance insomnia, but can cause hangover drowsiness • Antihistamines: diphenhydramine is sedating • Low dose Doxepin 3 or 6 mg also works thru histamine receptor • Melatonin short ‐ acting approx 2 hours so for sleep onset; melatonin receptor • CBD: minimal research; cannabinoid receptor • Orexin receptor antagonists: suvorexant and lemborexant have longer half ‐ life • Orexin and Hypocretin are 2 names for same hypothalamic neurotransmitter
CANNABINOIDS CANNABINOIDS – min inim imal da data • Over 100 cannabinoids! • CBD – Cannabidiol – sedating, reduced sleep latency; no euphoria • From Hemp or Marijuana: legal status in flux; “Supplement” so not regulated • CBN – Cannabinol: sedating, reduced pain, increased appetite • THC – Tetrahydrocannabinol: euphoria, reduced pain/nausea • Variable effects on sleep stages • Dronabinol (Marinol) is synthetic analog which is FDA ‐ approved
CBD CBD FO FOR IN INSOMNIA IA • No good data on efficacy or sleep stages; tolerance likely develop • Established for Chronic Pain, with small effect size • SR Snitzman et al. BMJ Supportive Palliat Care 2020;0:1 ‐ 6 • Case series from Colorado • 103 adult patients in psychiatry clinic – Anxiety or Sleep issues • Mean age 34 ‐ 36 • CBD capsule 25 ‐ 75 mg • Mild improvement in anxiety and sleep scores over 1 ‐ 3 months • 79% reported improved anxiety; 15% reported worse anxiety • 66% reported improved sleep; 25% reported worse sleep • S Shannon et al. Permanente J. 2019;23:18 ‐ 41
EV EVALI ALI e ‐ Vaping ping Acut Acute Lun Lung Inju Injury ry: Bilateral infiltrates; Ask about Cigarettes and Vaping! LAYDEN; NEJM 2019
nd Or ant ‐ 2 nd Lem Lembor orexan Orexin Re Receptor An Antagoni gonist R Rosenberg et al. JAMA Network Open 2019. Lemborexant vs Zolpidem ER vs Placebo
LEMBOREXANT Results • Placebo group improves, which is consistent with prior insomnia research, since insomnia waxes and wanes over time! • Lemborexant superior for falling asleep and staying asleep compared to placebo • Lemborexant half ‐ life 17 ‐ 19 hours; no driving impairment in testing; (Suvorexant half ‐ life 12 hrs)
Which blood test is recommended for RLS? • A. TSH • B. Dopamine • C. Ferritin • D. CBC with MCV • E. Creatinine
RE RESTLE TLESS SS LE LEGS GS SYNDR SYNDROME ME (RLS) (RLS) • “Abnormal discomfort” • Uncomfortable, distressing and hard to describe • Insomnia is typically present • Urge to move • Induced by Rest • Relieved by movement • Worse at night • Causes: • Genetic: can run in families; Autosomal dominant • Secondary: pregnancy, neuropathy; renal failure; Parkinson’s
TRE TREATM TMEN ENT OF OF RE RESTLE LESS SS LE LEGS SYNDR SYNDROME ME RLS: Wijemanne. Pract Neuro 2017;17:444 ‐ 452 • Iron deficiency may worsen RLS (serum ferritin) • If ferritin <75, give iron (with Vit C) with goal of ferritin >100 • Symptoms may worsen on antidepressants • Also avoid caffeine and alcohol • Behavioral: • Stretch before bed; consider short bath • Medications: • Dopaminergic agents • Pramipexole, ropinirole, carbidopa/levodopa, rotigotine • Clonazepam • Gabapentin • Opiates
OBSTRUC OBSTRUCTIVE SLEEP SLEEP APNE APNEA
KEY OSA DEFINITION Apnea: complete cessation of airflow lasting 10 seconds or more • Hypopnea: reduced airflow ( ≥ 30%) for 10 seconds or more, • associated with ≥ 4% oxygen desaturation (4% is classical definition) Apnea ‐ Hypopnea Index (AHI) : the number of apneas and • hypopneas per hour of sleep Normal AHI < 5 – Mild 5 ‐ 14 – Moderate 15 ‐ 29 – Severe ≥ 30 –
Which of the following is NOT in STOPBANG? • A. Apnea (witnessed) • B. Falling asleep while driving • C. Tired (fatigue) • D. Hypertension • E. BMI>35
CLIN CLINIC ICAL PREDICTO PREDICTORS RS OF OF OSA OSA ht http://www. www.st stopbang.ca opbang.ca/os osa/ a/screeni reening. g.php php STOPBANG – 8 Questions High risk: yes to 5 ‐ 8 questions; Medium risk yes on 3 ‐ 4;Low risk yes on 0 ‐ 2 Snoring Tired (fatigue) Observed Apnea Pressure (Hypertension) BMI >35 ( ≥ 30 is considered obese) Age >50 Neck size > 17 inches for men or >16 inches for women Gender male
CLINICAL PREDICTORS OF OSA • Screening questionnaires • Epworth Sleepiness Scale: range 0 ‐ 24 for 8 questions – Normal score < 10 – In OSA population, score correlates with AHI – SLEEP 1991; 14(6):540 ‐ 5 • Berlin 10 questions validated in primary care – Snoring, apnea, fatigue, sleepiness at wheel, Hypertension – Ann Intern Med. 1999 Oct 5;131(7):485 ‐ 91 • STOP ‐ BANG used in Anesthesia – Snoring, Tired, Observed apnea, Pressure (HTN), BMI 35, Age 50, Neck circumference 40 cm (15.75 inches), Gender (male) – Arch Otolaryngol Head Neck Surg. 2010 Oct: 136(10):1020 ‐ 4
OSA OSA and and Hypertensi Hypertension on • Numerous cohort and observational studies show strong association between OSA and HTN • The higher AHI, the higher the likelihood of HTN (dose dependent relationship) : • AHI 5 ‐ 15 odds ratio of HTN 2.0 • AHI ≥ 15 odds ratio of HTN 2.9 • Resistant HTN (difficult to treat requiring 3 drugs at max doses) is associated with OSA in 70 ‐ 80% of patients Peppard PE et al NEJM 2000 Janssen C et al Journal of Hypertension 2017 Moon C et al Clinical Nurse Specialist 2016
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