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Source: Dopp JM, Phillips BG. Sleep-Wake Disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017.


  • Common causes of insomnia: Concomitant psychiatric disorders, significant psychosocial stressors, excessive alcohol use, caffeine intake, and nicotine use

    • Sleep hygiene: Relax before bedtime, exercise regularly, regular bed/wake-up time, no alcohol/caffeine/nicotine

    • ± drug therapy

  • Benzodiazepine (BZD) receptor agonist tolerance and dependence are avoided by using low-dose therapy for shortest duration possible.

    • Long-acting BZDs should be avoided in elderly.

  • Obstructive sleep apnea (OSA)

    • May be independent risk factor for development of hypertension

      • If hypertension present, often refractory to drug therapy until sleep-disordered breathing is alleviated.

    • First line is nasal continuous positive airway pressure (PAP).

      • Weight loss also encouraged in obese patients.

  • Narcolepsy pharmacologic management

    • Treat excessive daytime sleepiness (EDS).

    • Treat rapid eye movement (REM) sleep abnormalities.

  • First line for travel jet lag is a short-acting benzodiazepine receptor agonist, ramelteon, or melatonin.

  • First line for restless legs syndrome (RLS) is dopamine agonists.


  • Sleep cycles

    • Two phases: Nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep

      • NREM: 4 stages of sleep with stage 1 being between wakefulness and sleep to stage 3 or 4 with delta sleep or slow-wave sleep where metabolic activity and brain waves slow with no eye movement and low tonic muscle activity

      • REM: Dramatic physiologic change from NREM where brain becomes electrically and metabolically activated

        • REM cycles tend to lengthen in later stages of sleep cycle

    • Each night ~4–6 cycles of NREM and REM sleep

    • Each cycle ~70–120 min

  • Circadian rhythm

    • At birth: 20 hours a day sleeping

    • 3–6 months: Differentiation between REM and NREM sleep

    • 3 years: Ultradian sleep-wake rhythm changes to circadian pattern

    • Sleep-wake cycle lasts about 25 hours in environments devoid of light cues

    • Elderly have lighter and more fragmented sleep

  • Neurochemistry

    • NREM mediated neurotransmitters: GABA and adenosine

    • REM mediated by: cholinergic cells and noradrenergic pathways

    • Dopamine has an alerting effect (decrease for sleepiness).

    • Wakefulness: Norepinephrine and acetylcholine

  • Polysomnography (PSG)

    • PSG is a study used to assess and record variables that characterize sleep and aid in sleep disorder diagnosis.

  • Classification of sleep disorders

    • The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for diagnosis

      • 10 categories of sleep-wake disorders


  • Most common complaint in general medical practice

  • Causes distress (fear/inability of not being able to fall asleep and impaired work-related productivity due to daytime fatigue or drowsiness)

  • Characterized as difficulty falling asleep, difficulty maintaining sleep, or experiencing nonrestorative sleep

  • <3 months = short term; >3 months = chronic


  • Primary insomnia begins early or middle adulthood.

  • Symptoms occur in 33% to 50% of adult population.

  • 40% have concurrent ...

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