Sleep Science and Stages Overview

Sleep-Wake Disorders

• A presentation on sleep-wake disorders.
• Objectives of the presentation include: defining sleep disorders, understanding differences between various sleep disorders, diagnosis and treatment of sleep disorders, reviewing therapy plans and selecting appropriate therapy for each patient.

Stages of Sleep

• Non-REM sleep accounts for 75% of total sleep.
• REM sleep accounts for 25% of total sleep.
• The four stages of sleep are presented, illustrating the transition from falling asleep to REM sleep.

Non-REM Sleep

• N1: Transition from wakefulness to deeper sleep, lasting 15-30 minutes.
• N2: Intermediate sleep, featuring sleep spindles and K-complexes on EEG.
• N3 (and sometimes N4): Deep sleep (delta sleep), characterized by delta waves on EEG, and crucial for restoration (e.g., protein synthesis, wound healing, immune function).

REM Sleep

• Characterized by inactivity of voluntary muscles (except extraocular muscles).
• Features rapid eye movements and dreaming.
• Two states: phasic (sympathetic nervous system bursts, blood pressure & heart rate fluctuations) and tonic (parasympathetically driven, decreased EEG amplitude, atonia).

Physiological Changes During Sleep

• Autonomic activity: non-REM sleep features slow, regular heart rate and respiration rates, and blood pressure, while REM sleep displays irregular fluctuations.
• Neuroendocrine activity: cortisol levels lowest at sleep onset, growth hormone released during delta sleep; melatonin secretion highest during sleep, suppressed by light.
• Body temperature: lowest in early morning REM sleep, shows a cooling trend from non-REM to REM stages.

Sleep Changes with Age

• Sleep quantity and quality decline with age.
• Sleep stage N3 (deep sleep) decreases.
• Sleep stage N1 (light sleep) increases.
• The number of arousals and wakefulness also increases.

Theories of Sleep

• Restorative theory: tissues are restored and prepared for the following day.
• Adaptive theory: increases survival by minimizing metabolic processes during inactivity.
• Energy conservation theory: low metabolic rate during sleep conserves energy.
• 7 hours of sleep might be optimal for health.

Risks of Poor Sleep

• Increased mortality.
• Increased heart attacks.
• Increased accidents (similar to alcohol impairment).
• Obesity (increased cortisol, insulin resistance).
• Worsened pain conditions.
• ADHD symptomatology.

Sleep Studies: Measurement of Sleep and Sleepiness

• Polysomnography (PSG): measures various physiological variables (brain activity, breathing, airflow).
• Multiple sleep latency test (MSLT): measures daytime sleepiness.
• Maintenance of wakefulness test (MWT): measure how long one can stay awake.

Sleep Parameters

• Sleep onset latency (SOL): time to fall asleep.
• Latency to persistent sleep (LPS): time from lights off until 10 minutes consistent sleep.
• Total sleep time (TST): total time spent asleep.
• Wake time after sleep onset (WASO): time awake during the night.
• Sleep efficiency (SE): ratio of TST to total time in bed (normal SE is >85%).

Polysomnography

• Simultaneous recording of physiological variables with electrodes.
• Measurements include: airflow, breathing effort, oxygen saturation, leg movements, ECG, and body position.

Multiple Sleep Latency Test (MSLT)

• Objective measure of daytime sleepiness.
• Measures the response to 5 opportunities, observed across 20-minute naps.
• A latency below 5 minutes indicates severe sleepiness.

Maintenance of Wakefulness Test (MWT)

• Measures the ability to stay awake.
• Patients remain awake in a darkened room for as long as possible.

Standardized Rating Scales

• Pittsburgh Sleep Quality Index (PSQI): assesses sleep quality.
• Epworth Sleepiness Scale (ESS): measures daytime sleepiness.
• Stanford Sleepiness Scale (SSS): measures daytime sleepiness.
• Insomnia Severity Index (ISI): measures the severity of insomnia.
• Dysfunctional Beliefs and Attitudes about Sleep Questionnaire (DBAS): measures insomnia-related beliefs.

Insomnia Severity Index (ISI)

• 7-item scale used to assess the severity of the Insomnia experience.
• Range 0 to 28 with scoring and interpretation criteria provided.

Pittsburgh Sleep Quality Index (PSQI)

• A validated self-report questionnaire to evaluate sleep quality.
• Questions covering various aspects of sleep habits are asked.

Epworth Sleepiness Scale

• Self-reported scale measuring daytime sleepiness.
• Measures responses to 8 standardized scenarios.

Treatment Goals

• Improve sleep quality and time.
• Improve daytime impairments (e.g., energy, attention, memory).
• Reduce sleep latency and wakefulness after sleep onset.
• Improve symptomatic symptoms (e.g., fatigue).
• Increase total sleep time.

Sleep Disorders

• Insomnia disorder
• Narcolepsy
• Circadian rhythm sleep-wake disorder
• Hypersomnia
• Breathing-related sleep disorder
• Rapid eye movement sleep behavior disorder
• Restless legs syndrome
• Nightmare disorder
• Sleep terror disorder
• Sleepwalking disorder

Insomnia Disorder

• Subjective report of sleep initiation, duration, consolidation, or quality difficulties.
• Despite adequate sleep opportunities, it results in daytime impairment.

Transient/Short Term/Long Term Insomnia

• Timeline classification of insomnia based on duration.

Risk Factors for Insomnia

• Situational factors (travel, stress).
• Medical conditions (pain disorders).
• Psychiatric factors (moods disorders).
• Pharmacologically induced factors (medication use).

Neurotransmitter Pathophysiology

• Wake-promoting substances: norepinephrine, acetylcholine, histamine, dopamine, orexin.
• Sleep-promoting substances: GABA, adenosine, melatonin.

Signs and Symptoms of Insomnia

• Difficulty falling asleep.
• Difficulty maintaining sleep.
• Frequent awakening.
• Waking up too early.
• Excessive daytime sleepiness.
• Difficulty concentrating.
• Memory impairment.

Nonpharmacological Treatments for Insomnia

• Stimulus control procedures: establish regular sleep schedule, avoid daytime naps, and relaxing activities before bed.
• Sleep hygiene recommendations: exercise regularly, create a comfortable sleep environment, avoid alcohol, caffeine, and nicotine before bed, and relaxed bedtime routine.

Pharmacological vs Nonpharmacological Treatment

• Pharmacotherapy (often short-term; effective during treatment duration).
• Cognitive Behavioral Therapy (CBT) (often more sustained improvement).

Pharmacological Treatment for Insomnia

• Short-to-intermediate acting benzodiazepine receptor agonists or melatonin receptor agonists.

Benzodiazepines

• Medication (drugs) used to treat insomnia, with approved FDA uses, doses, and durations.

Benzodiazepine receptor agonists (BzRAs)

• Medication (drugs) used to treat insomnia; specific medications, approved FDA uses, doses, and durations are provided.
• (BzRAs) (medication) include specific types and their durations of use, approved by the FDA.

Adverse Events from Sleep Medications

• Benzodiazepines: CNS depression, tolerance, rebound insomnia, psychomotor impairment, respiratory depression, paradoxical reactions, sleep-related behavior.
• Non-benzodiazepines: headache, next-day somnolence, sleep-related behavior, hallucinations, unpleasant taste.

Pregnancy/Lactation Considerations

• Benzodiazepines and Non-benzodiazepines (medication) have potential risks during pregnancy and lactation.

Melatonin Receptor Agonist (Ramelteon)

• Short to intermediate acting.
• Used to treat sleep-onset insomnia.
• Maximum effects may take up to three weeks.
• Potential concerns, including sleep-related activities, abnormal thoughts, and worsening depression in sensitive patients.

Doxepin

• Low-dose TCA/selective H1 antagonist activity.
• Sleep maintenance medication; is taken with a high-fat meal and can delay Tmax by about 3 hours.
• Has CYP2C19 interactions.
• Dosage: adults (6 mg); elderly (3 mg).
• Contraindications include: severe urinary retention, untreated narrow-angle glaucoma, and severe sleep apnea.

Suvorexant

• Orexin receptor antagonist.
• Taken 10 mg (sometimes 20 mg) nightly, at least 7 hours before bedtime.
• Used for treating insomnia.
• Contains potential interactions with CYP3A4 and may induce similar adverse sleep behaviors.

Antidepressants

• Used in reduced dosages for treating insomnia.
• Not FDA approved for insomnia treatment.

OTC Products

• Antihistamines (diphenhydramine, doxylamine): potential anti-cholinergic effects, and possible tolerance after long durations.
• Valerian: promotes GABA activity, and has inconsistent effects on sleep latency.
• Melatonin: promotes melatonin; shows little effect on sleep latency / duration.

Duration of Treatment for Insomnia

• Initial treatment period (generally 2-4 weeks).
• Continuous or ongoing therapy (visits monitored), if chronic insomnia is present.

Discontinuation of Sleep Medications

• Tapering of dose and frequency of use (avoiding rebound insomnia and withdrawal).
• Possible recurrence or worsening of symptoms; physical or psychological withdrawal reactions.

Narcolepsy

• Irresistible attacks of refreshing sleep nearly daily.
• Excessive daytime sleepiness.
• Cataplexy (sudden loss of muscle tone).
• Abnormal manifestations of REM sleep (hallucinations, sleep paralysis).

Treatment of Excessive Daytime Sleepiness (EDS)

• Naps (scheduled).
• Modafinil or other medications (careful with CNS/cardiovascular patients).
• Methylphenidate/amphetamine may cause more side effects than Modafinil.
• Use caution in cardio/cerebrovascular disease or seizures.

Treatment of REM-Associated Effects

• Cataplexy: sodium oxybate (FDA approved, abuse risk).
• Unapproved options include TCAs, SSRIs, and SNRIs, and small-dose selegiline.

Circadian Rhythm Sleep-Wake Disorder

• Misaligned sleep-wake cycles with societal norms.
• Napping throughout the 24-hour period.
• Potentially caused by shift work, jet lag, or substance abuse.

Melatonin Receptor Agonist (Tasimelteon)

• FDA-approved for treating insomnia.
• M1 and M2 receptor agonist; 20 mg/day.
• Potential adverse reactions (especially in the elderly).
• Limited potential for abuse.

Obstructive Sleep Apnea Hypopnea

• Repetitive upper airway collapses during sleep.
• Obvious symptoms such as snoring, and morning headaches.
• Associated with obesity, large neck sizes, coexisting hypertension, or hypothyroidism.

Complications of Obstructive Sleep Apnea Hypopnea

• Health risks (due to poor sleep quality).
• Hypertension (often resistant to treatment), heart failure, and stroke.
• Increased likelihood of cardiovascular events.

Obstructive Sleep Apnea Hypopnea Treatment

• Continuous positive airway pressure (CPAP) or BiPAP therapy (first-line treatment).
• Weight management.
• Oral devices.
• Surgical therapy (tracheostomy).
• Modafinil (for symptom relief).

Rapid Eye Movement Sleep Behavior Disorder

• Acting out dreams during sleep.
• Violent movements possible in sleep.

Restless Legs Syndrome (RLS)

• Feelings of restlessness, burning, tingling, and aches in legs, often before sleep onset.
• Symptoms worsened in evenings/rest periods.
• Can be worsened with low iron levels.

RLS Medication Options

• Dopamine agonists (first line).
• Anticonvulsants (first line if with seizures).
• Hypnotic agents.
• Opioids (not first-line treatment).