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Monday, August 18, 2025

Sleepiness


Sleepiness (Excessive Daytime Sleepiness / Hypersomnolence)

Introduction

Sleepiness is defined as an increased propensity to fall asleep or difficulty maintaining wakefulness during daytime activities that should normally require alertness. It can manifest as frequent yawning, reduced concentration, unintentional dozing, or even sleep attacks. While mild, transient sleepiness is common after inadequate sleep or physical exertion, persistent or excessive daytime sleepiness (EDS) may indicate underlying sleep disorders, systemic illness, or neurological conditions.

Sleepiness is distinct from fatigue. Fatigue refers to physical or mental exhaustion without necessarily an increased drive to sleep, whereas sleepiness reflects impaired sleep–wake regulation. Clinically, this distinction is essential for diagnosis and management.

Sleep Physiology and Regulation

  • Circadian rhythm: Controlled by the suprachiasmatic nucleus of the hypothalamus, synchronizing sleep–wake cycles with environmental cues (light, temperature).

  • Sleep homeostasis: Accumulation of sleep pressure with prolonged wakefulness, relieved by sleep.

  • Neurotransmitters:

    • Wake-promoting: norepinephrine, dopamine, histamine, orexin.

    • Sleep-promoting: GABA, adenosine.

  • Disruption of any of these systems can result in pathological sleepiness.

Etiology of Sleepiness

1. Lifestyle and Behavioral Factors

  • Insufficient sleep due to voluntary sleep deprivation (work schedules, social habits).

  • Shift work disorder (circadian misalignment).

  • Jet lag.

2. Sleep Disorders

  • Obstructive Sleep Apnea (OSA): Recurrent airway obstruction leads to sleep fragmentation and hypoxemia.

  • Narcolepsy: Hypocretin (orexin) deficiency; excessive sleepiness with cataplexy, sleep paralysis, hallucinations.

  • Idiopathic hypersomnia: EDS without identifiable cause.

  • Restless Legs Syndrome (RLS) / Periodic Limb Movement Disorder: Sleep disruption from involuntary limb movements.

  • Insomnia: Poor sleep quality leads to residual sleepiness.

3. Medical and Psychiatric Causes

  • Neurological disorders: Parkinson’s disease, Alzheimer’s disease, stroke, traumatic brain injury.

  • Psychiatric illness: Depression, bipolar disorder, anxiety disorders.

  • Endocrine/metabolic disorders: Hypothyroidism, diabetes mellitus, anemia.

  • Chronic organ failure: Chronic kidney disease, chronic liver disease, heart failure.

4. Medication- or Substance-Induced

  • Sedating medications:

    • Antihistamines (diphenhydramine, hydroxyzine).

    • Benzodiazepines (diazepam, lorazepam).

    • Antidepressants (tricyclics, mirtazapine).

    • Antipsychotics (quetiapine, olanzapine).

    • Antiepileptics (gabapentin, valproate).

    • Opioids.

  • Substance use: Alcohol, cannabis, recreational drugs.

  • Withdrawal states: From stimulants such as caffeine or amphetamines.

5. Rare/Inherited Disorders

  • Klein–Levin syndrome (“Sleeping Beauty syndrome”).

  • Genetic predispositions to narcolepsy.

Clinical Presentation

  • Main symptom: Increased tendency to fall asleep during the day.

  • Unintended dozing while reading, watching TV, or even driving.

  • Poor concentration and memory lapses.

  • Morning headaches (suggestive of OSA).

  • Mood changes (irritability, depression).

  • Narcolepsy-specific features:

    • Cataplexy (sudden loss of muscle tone triggered by emotions).

    • Hypnagogic hallucinations.

    • Sleep paralysis.

Diagnostic Evaluation

1. History

  • Duration, onset, severity of sleepiness.

  • Sleep hygiene and daily schedule.

  • Snoring, witnessed apneas, restless sleep.

  • Medication/substance use.

  • Psychiatric or medical history.

2. Physical Examination

  • BMI and neck circumference (OSA risk factors).

  • ENT exam for airway obstruction.

  • Neurological exam (signs of neurological disease).

3. Questionnaires and Scales

  • Epworth Sleepiness Scale (ESS): >10 indicates excessive sleepiness.

  • Stanford Sleepiness Scale.

4. Laboratory and Sleep Studies

  • Polysomnography (overnight sleep study): Gold standard for diagnosing OSA, PLMS, parasomnias.

  • Multiple Sleep Latency Test (MSLT): Measures tendency to fall asleep; narcolepsy diagnosis if mean sleep latency <8 minutes and ≥2 sleep-onset REM periods.

  • Maintenance of Wakefulness Test (MWT): Measures ability to stay awake.

  • Blood tests: TSH, fasting glucose, CBC, renal/liver function.

Management

Treatment is directed at the underlying cause, supported by symptomatic therapy and lifestyle interventions.

1. General Lifestyle Measures

  • Sleep hygiene: Regular bedtime, quiet and dark environment, avoid screens before sleep.

  • Adequate sleep duration: 7–9 hours for adults.

  • Avoid alcohol and sedatives before sleep.

  • Caffeine use: Effective for mild sleepiness but should be limited to morning/early afternoon.

  • Weight loss: For patients with OSA.

2. Specific Treatments Based on Etiology

A. Obstructive Sleep Apnea (OSA)

  • Continuous Positive Airway Pressure (CPAP): Gold standard; prevents airway collapse.

  • Oral appliances: Mandibular advancement devices.

  • Surgical options: Uvulopalatopharyngoplasty, tonsillectomy, hypoglossal nerve stimulation.

B. Narcolepsy

  • Wake-promoting agents:

    • Modafinil 200–400 mg orally once daily in the morning.

    • Armodafinil 150–250 mg orally once daily in the morning.

  • Stimulants:

    • Methylphenidate 10–60 mg/day orally in divided doses.

    • Amphetamines (dextroamphetamine 5–60 mg/day orally, divided doses).

  • Cataplexy management:

    • Sodium oxybate (gamma-hydroxybutyrate) 4.5–9 g nightly, divided into two doses.

    • Antidepressants (SSRIs/SNRIs, e.g., Venlafaxine 75–150 mg/day orally).

C. Idiopathic Hypersomnia

  • Modafinil 200–400 mg daily orally.

  • Methylphenidate 10–60 mg/day orally in divided doses.

D. Restless Legs Syndrome / Periodic Limb Movement Disorder

  • Dopamine agonists:

    • Pramipexole 0.125–0.75 mg orally at bedtime.

    • Ropinirole 0.25–4 mg orally at bedtime.

  • Gabapentin 300–900 mg orally at bedtime.

E. Psychiatric Causes

  • Depression: SSRIs or SNRIs (e.g., Sertraline 50–200 mg/day orally).

  • Bipolar disorder: mood stabilizers (e.g., Lithium carbonate 300–600 mg orally 2–3 times daily).

F. Endocrine/Metabolic Causes

  • Hypothyroidism: Levothyroxine 25–200 mcg orally once daily.

  • Diabetes: glycemic control with insulin or oral hypoglycemics.

  • Anemia: iron supplementation (Ferrous sulfate 325 mg orally 1–3 times daily).

3. Symptomatic Pharmacological Therapy

  • Caffeine tablets: 100–200 mg orally as needed for alertness.

  • Modafinil/Armodafinil: First-line for residual sleepiness in OSA or idiopathic hypersomnia.

  • Solriamfetol: (new agent) dopamine/norepinephrine reuptake inhibitor, 75–150 mg orally once daily for EDS in OSA or narcolepsy.

  • Pitolisant: Histamine H3 receptor antagonist, 8.9–35.6 mg orally once daily, effective for narcolepsy.

Precautions and Counseling

  • Educate patients about risks of driving or operating heavy machinery when sleepy.

  • Avoid alcohol and sedatives that worsen drowsiness.

  • Stress adherence to CPAP in OSA patients.

  • Regular follow-up with sleep medicine specialists.

  • For stimulant therapy: monitor blood pressure, heart rate, and psychiatric status.

Drug Interactions

  • Modafinil/Armodafinil: Induce CYP3A4 → reduce efficacy of oral contraceptives, warfarin, some anticonvulsants.

  • Methylphenidate/Amphetamines: Interact with MAO inhibitors (hypertensive crisis); caution with SSRIs.

  • Sodium oxybate: CNS depressant; dangerous with alcohol, opioids, benzodiazepines.

  • Dopamine agonists (pramipexole, ropinirole): May interact with antipsychotics, increasing psychiatric symptoms.

  • SSRIs/SNRIs: Risk of serotonin syndrome with other serotonergic drugs.

  • Levothyroxine: Reduced absorption with calcium, iron supplements, proton pump inhibitors.

  • Ferrous sulfate: Interacts with tetracyclines, quinolones; reduces their absorption.

Prognosis

  • OSA-related sleepiness improves significantly with CPAP and weight reduction.

  • Narcolepsy and idiopathic hypersomnia are chronic but manageable with medications.

  • Psychiatric or endocrine-related sleepiness improves with treatment of the underlying condition.

  • Untreated chronic sleepiness increases risk of accidents, cardiovascular disease, and impaired quality of life.




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