Excessive daytime sleepiness

Excessive daytime sleepiness is the inability to stay awake and alert during the major waking periods of the day, resulting in unintended lapses into sleep. It is distinct from fatigue (lack of energy without an increased tendency to doze) and from tiredness (a normal response to exertion or lost sleep).

Clinical relevance. It affects 5 to 15% of adults, impairs work performance and mood, and increases the risk of collisions (drivers who sleep under 5 hours have a crash risk 4 to 5 fold higher). It is often treatable, and it is a hazard to safety-critical occupations.

Classification.

• Insufficient sleep and circadian disorders: insufficient sleep syndrome, shift work disorder, delayed sleep phase.
• Sleep-disordered breathing: obstructive sleep apnoea, central sleep apnoea, hypoventilation.
• Central disorders of hypersomnolence: narcolepsy type 1 (with cataplexy or low cerebrospinal fluid hypocretin-1), narcolepsy type 2, idiopathic hypersomnia, Kleine-Levin syndrome.
• Sleep fragmentation from other disorders: periodic limb movement disorder, restless legs syndrome, parasomnias, chronic pain, nocturia.
• Medical, neurological and psychiatric: hypothyroidism, anaemia, hypercalcaemia, uraemia, hepatic encephalopathy, hypoglycaemia, depression, bipolar disorder, Parkinson disease, neurodegenerative disease, post-traumatic hypersomnia, hypothalamic and brainstem lesions.
• Medicines and substances: sedative antihistamines, benzodiazepines, opioids, antiepileptics, antipsychotics, beta blockers, dopamine agonists (sleep attacks), alcohol, cannabis, and withdrawal from stimulants.

Mechanism. Sleepiness reflects the balance of homeostatic sleep pressure (adenosine accumulation with time awake), circadian alerting signals and the integrity of arousal circuits (hypothalamic hypocretin neurones, monoaminergic nuclei). Loss of hypocretin neurones (probably autoimmune, with HLA-DQB1*06:02 association) causes narcolepsy type 1 with unstable sleep and wake boundaries (cataplexy, sleep paralysis, hypnagogic hallucinations, sleep onset REM periods).

History.

• Pattern: onset (sudden or gradual), duration (over 3 months), situations in which sleep occurs (passive versus active tasks), unintended naps, refreshing quality of naps (typically refreshing in narcolepsy, unrefreshing in idiopathic hypersomnia).
• Total sleep time on work days and free days; catch-up sleep at weekends (suggests insufficient sleep); bedtime and wake time; shift work; caffeine and alcohol timing; screen use.
• Epworth Sleepiness Scale (0 to 24; 11 or more indicates excessive sleepiness; 16 or more severe).
• Narcolepsy features: cataplexy (sudden bilateral loss of muscle tone triggered by laughter or surprise with preserved consciousness), sleep paralysis, vivid hypnagogic hallucinations, automatic behaviour, fragmented night sleep, weight gain, onset in teens to twenties.
• Sleep apnoea features: snoring, witnessed pauses, nocturia, morning headache.
• Restless legs syndrome and periodic limb movements: urge to move legs, worse at rest in the evening, relieved by movement; bed partner reports kicking.
• Mood: low mood, anhedonia, atypical depression with hypersomnia.
• Medicines (every drug, including over the counter), alcohol, cannabis.
• Past: head injury, infection (infectious mononucleosis, encephalitis), stroke, multiple sclerosis, Parkinson disease, hypothyroidism, autoimmune disease.
• Safety: drowsy driving, near misses, falls, occupational hazards.

Examination.

• BMI, neck circumference, blood pressure, Mallampati class, tonsils, retrognathia.
• Thyroid, pallor, jaundice, signs of liver or renal disease, features of Cushing syndrome or acromegaly.
• Neurological: parkinsonism, focal deficits, eye movements (brainstem), cataplexy sign (knee buckling, facial drooping with emotion).
• Mood and cognition screen.

Red flags.

• Sleepiness while driving, collision or near miss, safety-critical occupation.
• Cataplexy, sleep paralysis with hallucinations (narcolepsy).
• Sudden onset after head injury, stroke or infection; new focal neurology or headache; papilloedema.
• Hypersomnia with episodes of hyperphagia, disinhibition or confusion lasting days (Kleine-Levin syndrome).
• Weight loss, night sweats (lymphoma, malignancy) or fever.
• Daytime hypoxia or hypercapnia, polycythaemia.
• Suicidal thoughts or severe depression.
• New sleepiness after starting dopamine agonists or sedatives.

• Most frequent: insufficient sleep, obstructive sleep apnoea, shift work, sedating medicines, alcohol, depression.
• Disorders of hypersomnolence: narcolepsy type 1 and type 2, idiopathic hypersomnia, Kleine-Levin syndrome, hypersomnia due to a medical disorder (Parkinson disease, Prader-Willi syndrome, myotonic dystrophy, hypothalamic tumour, brain injury).
• Sleep fragmentation: restless legs, periodic limb movement disorder, pain, nocturia, nocturnal seizures, parasomnia, insomnia with daytime sleepiness.
• Endocrine and metabolic: hypothyroidism, diabetes, hypercalcaemia, hyponatraemia, uraemia, hepatic encephalopathy, hypoglycaemia, adrenal insufficiency, vitamin B12 deficiency.
• Haematological and infectious: anaemia, iron deficiency (with or without anaemia), infectious mononucleosis, HIV, post-viral fatigue.
• Neurological: Parkinson disease and other neurodegenerative disease, multiple sclerosis, stroke, epilepsy, traumatic brain injury, intracranial mass.
• Mimics: chronic fatigue syndrome (no increase in sleep propensity), depression, cancer-related fatigue, heart failure, anaemia, long-term conditions.

1. Confirm true sleepiness: Epworth Sleepiness Scale, two-week sleep diary (bed and wake times, naps, caffeine, alcohol, medicines) and, where available, actigraphy for 14 days.
2. Baseline blood tests: full blood count, ferritin, urea and electrolytes, calcium, liver profile, glucose or glycated haemoglobin, thyroid stimulating hormone, vitamin B12, folate, 9 am cortisol if adrenal disease is suspected, creatine kinase if muscle disease is suspected; HIV test if risk factors are present.
3. Screen for sleep apnoea: STOP-BANG then home polygraphy or polysomnography.
4. Review medicines and substances; urine toxicology if substance use is suspected.
5. Mood screening (PHQ-9 of 10 or more is positive) and cognitive screen.
6. Where central hypersomnolence is suspected, or after sleep apnoea is treated and sleepiness persists: overnight attended polysomnography followed the next day by a multiple sleep latency test (four or five naps at 2 hour intervals). Narcolepsy: mean sleep latency of 8 minutes or less and two or more sleep-onset REM periods (counting the one in the preceding night). Withdraw stimulants, REM-suppressing antidepressants and other relevant drugs at least 2 weeks before (following discussion with the prescriber), and ensure 1 or more weeks of sleep diary or actigraphy confirming at least 6 hours/night beforehand.
7. HLA typing (HLA-DQB1*06:02 is present in over 90% of narcolepsy type 1 but also in about 25% of the general population) and lumbar puncture for cerebrospinal fluid hypocretin-1 (110 pg/mL or less, or under one third of normal values) when the multiple sleep latency test is equivocal.
8. Neuroimaging (magnetic resonance imaging of brain) if focal neurology, headache, hypothalamic features or sudden onset; electroencephalogram if seizures are suspected.
9. Iron studies and a ferritin target of over 75 micrograms/L in restless legs syndrome.

Limits. The multiple sleep latency test is affected by insufficient sleep, shift work, drugs and sleep apnoea, producing false positives (up to 3 to 5% of healthy adults have two sleep onset REM periods). Epworth scores are subjective and correlate only modestly with objective sleepiness. Repeat testing may be needed.

Immediate safety. Advise not to drive until sleepiness is controlled; the licensing authority must be informed for conditions causing sleepiness at the wheel, and for narcolepsy. Review safety-critical work with occupational health.

General measures for all.

• Sleep for 7 to 9 hours on a regular schedule; keep the same wake time at weekends; avoid caffeine after midday and alcohol near bedtime; maintain a dark, quiet cool bedroom; avoid screens in the hour before bed.
• Scheduled short naps (15 to 20 minutes) at low points in the afternoon, particularly in narcolepsy.
• Treat or remove the cause: dose reduction or switch of sedating drugs; treat depression, hypothyroidism (levothyroxine 25 to 50 micrograms daily titrated by thyroid stimulating hormone), anaemia, iron deficiency (ferrous sulphate 200 mg once or twice daily, or on alternate days); correct hypercalcaemia or renal failure.
• Obstructive sleep apnoea: CPAP (auto-titrating 4 to 20 cmH2O); weight loss.
• Restless legs syndrome: replace iron to a ferritin over 75 micrograms/L (intravenous ferric carboxymaltose 500 to 1000 mg if oral therapy fails), stop provoking drugs, and use gabapentin 300 mg at night titrated to 1800 mg or pregabalin 75 mg at night titrated to 300 mg in preference to dopamine agonists, which risk augmentation.

Narcolepsy and idiopathic hypersomnia (specialist initiated).

• Modafinil 100 mg each morning, increased by 100 mg weekly to 200 mg (up to 400 mg/day in one or two doses; the second dose no later than early afternoon). Modafinil reduces the effectiveness of hormonal contraception (cytochrome P450 3A4 induction), so use additional contraception during treatment and for 2 months after stopping.
• Pitolisant 4.5 mg each morning, increased weekly to 9 mg, 18 mg and a maximum of 36 mg once daily; useful for cataplexy as well as sleepiness; QT prolongation caution.
• Solriamfetol 75 mg once daily on waking, increased after at least 3 days to a maximum of 150 mg; monitor blood pressure and heart rate.
• Sodium oxybate: 4.5 g/night divided into two doses (at bedtime and 2.5 to 4 hours later), increased by 1.5 g/night each week to 6 to 9 g/night, effective for cataplexy, sleepiness and fragmented sleep; contraindicated with alcohol or other sedatives; risk of respiratory depression, sodium load (a 9 g dose delivers about 1.6 g sodium), and misuse.
• Cataplexy: venlafaxine 37.5 mg daily increased to 75 to 150 mg, or fluoxetine 20 mg, or sodium oxybate or pitolisant. Do not stop antidepressants abruptly (cataplexy rebound, status cataplecticus).
• Dexamfetamine 5 mg once or twice daily, increased weekly as tolerated under specialist supervision, as a later option with cardiovascular review.

Shift work and circadian disorders. Timed bright light, planned sleep, melatonin 2 mg modified-release at the target bedtime, and strategic caffeine; modafinil 200 mg 30 to 60 minutes before the shift for shift work disorder.

Monitoring. Epworth Sleepiness Scale and driving status at each visit; blood pressure, heart rate and weight on stimulants; liver profile and mood on sodium oxybate; drug holidays and abuse risk review; ECG on pitolisant if QT-prolonging drugs are used.

Referral and escalation. Sleep medicine for suspected narcolepsy, idiopathic hypersomnia, persistent sleepiness despite treated sleep apnoea or after correcting contributors, or atypical presentations; neurology for focal findings or secondary hypersomnia; psychiatry for depression or bipolar disorder; occupational health for safety-critical roles; endocrine for pituitary or thyroid disease.

Admission or disposition. Outpatient care is usual. Admit for diagnostic polysomnography as an inpatient only when testing cannot be arranged otherwise or for an acute neurological syndrome.

Safety netting. Do not drive or operate machinery while sleepy; stop and take a 15 minute rest or a caffeinated drink before continuing if drowsy while driving, but arrange a safe alternative. Report cataplexy, falls, hallucinations, sleep paralysis, sudden onset sleepiness, severe headache, weakness or visual disturbance, new low mood or suicidal thoughts.

Special groups.

• Adolescents and young adults: delayed sleep phase and insufficient sleep are common; narcolepsy often begins here.
• Pregnancy: avoid modafinil, pitolisant, solriamfetol and sodium oxybate where possible because of limited safety data; manage restless legs with iron.
• Older adults: lower starting doses of stimulants; assess for dementia, Parkinson disease, cardiac and respiratory disease.
• Parkinson disease: reduce dopamine agonist dose, consider modafinil 100 to 200 mg.
• Shift workers: discuss schedules, light exposure and strategic naps with occupational health.