GC165 I Can’t Fall Asleep Sleep Physiology And Sleep Disorders
Sleep physiology encompasses the neurobiological mechanisms regulating the sleep-wake cycle, including circadian and homeostatic processes, while sleep disorders such as insomnia, narcolepsy, and obstructive sleep apnea represent disruptions in these processes leading to impaired sleep initiation, maintenance, or quality.
Sleep Physiology and Sleep Disorders (GC 165)
This lecture by Dr. KF Chung (HKU Psychiatry) covers the fundamental physiology of sleep and the major sleep disorders you will encounter clinically. It is a "bread-and-butter" psychiatry lecture that integrates neuroscience (circadian rhythm, neurotransmitters, sleep architecture), clinical psychiatry (insomnia, narcolepsy, parasomnias), respiratory medicine (obstructive sleep apnoea), and pharmacology (Z-drugs, CBT-I). For exams, this lecture commonly yields questions on: the two-process model, sleep architecture, DSM-5 insomnia criteria, the 3P model, narcolepsy tetrad, OSA diagnosis/severity grading, NREM vs REM parasomnia differentiation, and pharmacology of Z-drugs.
Learning Objectives (from lecture slide): [1]
- Learn the basics of sleep physiology
- Learn the diagnosis and treatment of some common sleep disorders
How this fits into clinical practice: A patient saying "I can't fall asleep" is one of the commonest complaints in primary care, psychiatry, and general medicine. The clinician must distinguish primary insomnia from comorbid insomnia (depression, anxiety, pain, OSA), identify red flags for narcolepsy or REM sleep behaviour disorder (neurodegeneration risk), and institute appropriate stepped-care management.
1. Sleep Physiology
"Sleep is a normal physiological drive. All animals even single-cell organisms have a rest-activity cycle but the timing, amount and type of sleep vary dramatically across species." [1]
Why this matters: Sleep is not a luxury or a learned behaviour — it is biologically conserved. Understanding this prevents you from dismissing sleep complaints as trivial.
"Sleep is a reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment. Sleep is associated with a typical pattern of physiological and behavioral processes." [1]
Key words for exam: reversible, perceptual disengagement, unresponsiveness. This distinguishes sleep from coma (not easily reversible) and from anaesthesia (pharmacologically induced).
Brain regions controlling sleep-wake states (lecture diagram) [11]:
- Forebrain cortical & limbic areas (prefrontal cortex, amygdala, anterior cingulate, ventral striatum, inferior parietal, visual association cortex) → neuropsychology of dreaming
- Thalamocortical circuits → NREM sleep rhythms (EEG activation/deactivation)
- Hippocampal-cortical circuits → memory consolidation during sleep
- Hypothalamic nuclei — SCN, subparaventricular, dorsomedial nuclei → circadian rhythm generation; ventrolateral preoptic (VLPO), lateral hypothalamus, tuberomammillary nucleus, basal forebrain → sleep onset control
- Mesopontine nuclei — laterodorsal tegmental, pedunculopontine, dorsal raphe, locus coeruleus → REM-NREM cycle regulation
High Yield — Two-Process Model
"Two-process model. Circadian rhythm (Process C) is governed by the suprachiasmatic nucleus and under control by a set of clock genes. Key neurotransmitter is melatonin. Sleep-wake homeostasis (Process S) is a product of a complex network of brain regions and neurotransmitter pathways, which control sleep onset and maintenance. Key neurotransmitter is adenosine." [1]
| Feature | Process C (Circadian) | Process S (Homeostatic) |
|---|---|---|
| Structure | Suprachiasmatic nucleus (SCN) of hypothalamus | Complex network of brain regions |
| Key neurotransmitter | Melatonin | Adenosine |
| Mechanism | Internal biological clock ~24h, entrained by zeitgebers (light, temperature, social cues) | Accumulation of sleep-promoting substances with prolonged wakefulness |
| Daily pattern | Circadian alerting drive counteracts rising sleep pressure late in the day, then falls near habitual bedtime; a smaller post-lunch dip may occur | Builds across wakefulness and dissipates during sleep |
| Clinical relevance | Circadian rhythm disorders (DSWPD, jet lag, shift work) | Caffeine blocks adenosine receptors → promotes wakefulness |
Why adenosine? During wakefulness, neurons consume ATP. Adenosine is a metabolic by-product. It accumulates extracellularly and acts on A1/A2A receptors → inhibits wake-promoting neurons → promotes sleep drive. This is why caffeine (adenosine receptor antagonist) keeps you awake. [1][2]
Many body systems exhibit circadian rhythmicity (~24 hours), not just sleep-wake cycling. A lecture figure plots the following variables across a 24-hour period [11]:
| Variable | Nighttime Behaviour | Daytime Behaviour |
|---|---|---|
| Core body temperature | Falls to nadir ~36.5-36.6 °C | Higher in afternoon/evening |
| Melatonin | Rises to peak ~200 pmol/L | Near zero |
| Cortisol | Falls during early night | Sharp rise in early morning (peak ~150-170 µg/100 mL), then gradual decline |
| Growth hormone | Prominent pulsatile peaks (up to ~28 ng/mL) during sleep | Generally low |
| Thyrotrophin (TSH) | Rises during night (~3-3.5 mU/L) | Gradual decline during day |
| Urine volume | Falls to low level | Rises markedly |
| Systolic BP | Dips (nocturnal dipping) | Higher during waking hours |
Clinical relevance: an 8 am cortisol is used mainly when assessing the hypothalamic-pituitary-adrenal axis for adrenal insufficiency, not as a standard screening test for Cushing syndrome. Growth hormone secretion is coupled to slow-wave sleep, although growth and growth disorders cannot be inferred from a sleep trace alone.
Why melatonin? The SCN receives light input via the retinohypothalamic tract. The slide's pathway is multisynaptic: retina → SCN → hypothalamic autonomic relays → spinal intermediolateral column → superior cervical ganglion → pineal gland. Darkness permits sympathetic noradrenergic signalling to the pineal gland and melatonin synthesis; light suppresses it. The pituitary drawn nearby is an anatomical landmark, not the relay that carries the retinal signal to the pineal. [1]
"Process C: 2 peaks of sleepiness at 3pm and 3am. Process S: accumulation of sleepiness." [1]
Neuro-pathway regulating circadian rhythm: the lecture's lesion graph is about timing, not total abolition of sleep. An intact animal shows consolidated wake and sleep bouts, whereas after SCN lesion the same states are distributed almost evenly across 24 hours: the circadian organization is lost even though sleep itself persists. [1]
"An animal study showing the result of lesioning suprachiasmatic nuclei. Sleep occurs throughout 24 hours." [1]
Free-running experiments: In the slide's clock-free segment, the sleep period drifts later with an estimated period of 25.3 hours. The precise value is experiment-specific; the teaching point is that an endogenous rhythm persists without external time cues and normally needs zeitgebers, especially light, for 24-hour entrainment. [1]
High Yield — Sleep Stages and Architecture
"NREM & REM Sleep. NREM: Stage 1 to 4. Cycles every 90 mins. Stage 1 (2-5%); Stage 2 (45-55%); Stage 3 & 4 (13-28%); REM (20-25%); Wake ( < 5%). REM latency: 90 min. Shortened REM latency in depression (sleep phase delay hypothesis)." [1]
These are the lecture's historical Rechtschaffen-Kales stage labels. Current AASM staging uses N1, N2 and N3; old stages 3 and 4 are combined as N3. Percentages and 90-minute cycles are useful approximations, not fixed requirements for every patient or every cycle.
For sleep staging, EEG, EOG, and EMG are required [1] — this is the basis of polysomnography.
| Stage | % of Sleep | EEG Features | Key Points |
|---|---|---|---|
| Awake | — | Low-voltage, random, fast activity; alpha waves (8-12 Hz) when drowsy | Eyes-closed relaxed wakefulness → alpha rhythm |
| NREM Stage 1 | 2-5% | Theta waves (3-7 Hz); low-voltage mixed-frequency | Lightest sleep; transition from wakefulness; easy to arouse |
| NREM Stage 2 | 45-55% | Sleep spindles (12-14 Hz) and K-complexes | Largest proportion of sleep; body temp drops, HR slows |
| N3 (old Stages 3/4) | 13-28% in the lecture-era table | High-amplitude slow waves | Deep sleep / slow-wave sleep (SWS); hardest to arouse; predominates in first half of night |
| REM | 20-25% | Low-voltage, random, fast activity with sawtooth waves (resembles wake EEG) | Dreaming sleep; muscle atonia; rapid eye movements; predominates in second half of night |
"Sleep goes from NREM Stage 1, to 2, 3, 4 then REM (regarded as 1 NREM-REM cycle), then goes back to NREM Stage 1 and repeat itself. More NREM Stage 3 & 4 (deep sleep) in first half and more REM (dreaming sleep) in second half." [1]
Reading the PSG montage on the slide: wake shows relatively high chin EMG and eye movements; N1 has low-voltage mixed-frequency EEG with slow rolling eyes; N2 is identified by a sleep spindle and/or K-complex; N3 by high-amplitude slow waves; and REM combines low-voltage mixed-frequency EEG with bursts of rapid eye movements and markedly reduced chin EMG. The hypnogram is therefore a compressed stage-over-time display: N3 is concentrated early, while REM bouts lengthen toward morning.
Why does this distribution matter clinically?
- Parasomnias arising from NREM (sleepwalking, night terrors) tend to occur in the first half of the night when deep sleep predominates.
- Parasomnias arising from REM (RBD, nightmares, sleep paralysis) tend to occur in the second half when REM predominates.
- Timing is a useful clue, not a standalone diagnosis; stereotyped events, injury, atypical age of onset or diagnostic doubt may require video-PSG and consideration of nocturnal seizures.
- Depression classically shows shortened REM latency (REM appears earlier than 90 min), increased REM density, and decreased SWS. [1]
Age-related changes: [1]
- "More deep sleep" in young adults → "More broken sleep" in elderly
- With ageing: decreased total sleep time, decreased SWS, increased awakenings, increased Stage 1/2, more fragmented sleep. This is a normal physiological change but predisposes elderly to insomnia complaints.
"Sleep deprivation has serious effects on experimental animals… became weak and uncoordinated and lost the ability to regulate body temperature… metabolic rates became so high that they continued to lose weight." [1]
"Partial sleep deprivation and short sleep duration ( < 7 hrs vs. 7-8 hrs) is associated with mental and physical health risks, e.g., cardiometabolic diseases. Long sleep duration ( > 9 hrs) also has health risks." [1]
This is a U-shaped epidemiological association: both short and long reported sleep are associated with adverse outcomes, but the graph does not establish causation and long sleep may be a marker of illness. Sleep need varies between individuals; a universal “sweet spot” should not be inferred from this slide.
Rechtschaffen et al. (1983) — landmark animal study: Rats were forced to remain awake by rotating a disc every time they started to sleep. After 33 days of total sleep deprivation, all experimental rats died — demonstrating that sleep is essential for survival, not merely restorative. [11]
"Your sleep need is determined by sleeping and waking in a free-running manner for at least 1 week… If you feel tired or sleepy in the daytime, you haven't slept enough." [1]
Treat that last sentence as lecture shorthand: insufficient sleep is common, but persistent sleepiness despite adequate opportunity also warrants assessment for OSA, narcolepsy, circadian misalignment, medications/substances and medical or psychiatric disease.
"History taking, Physical and mental state examination, Blood test and imaging studies, Sleep investigation." [1]
2.1 Sleep Investigations
| Investigation | What It Measures | When to Use |
|---|---|---|
| Subjective scales — Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) | Self-reported severity of insomnia/sleepiness | Screening and monitoring |
| Sleep diary | Bed/wake times, sleep latency, awakenings, naps over 1-2 weeks | Insomnia, circadian disorders |
| Actigraphy (wearable device) | Movement-derived estimates of rest-activity patterns over days to weeks | Circadian rhythm disorders; adjunct in insomnia and MSLT preparation |
| Full-night Polysomnography (PSG) | EEG, EOG, chin/leg EMG, airflow, respiratory effort, SpO2, ECG | OSA when PSG is indicated; prerequisite to MSLT; video-PSG for suspected RBD/complex parasomnia; PLMS quantification |
| Home sleep apnoea test (HSAT) | Limited respiratory channels, usually without EEG sleep staging | Selected uncomplicated adults at increased risk of moderate-severe OSA; a negative/inconclusive/inadequate study requires PSG |
| Multiple Sleep Latency Test (MSLT) | Mean sleep latency across 4-5 naps at 2h intervals | Objective measure of sleepiness; narcolepsy diagnosis |
| Salivary dim light melatonin onset (DLMO) | Timing of melatonin rise | Circadian rhythm disorders |
How to read the actigraphy image: dense activity bars suggest wake/activity and quiet intervals suggest probable rest; the labelled nap is a daytime low-activity interval. Actigraphy estimates patterns from movement—it cannot show EEG-defined sleep stages and does not replace PSG when a physiological diagnosis is required.
"Pathological sleepiness: mean sleep latency < 5 min." [1]
That is the slide's older shorthand. MSLT interpretation is contextual: for narcolepsy the current physiological criterion is mean sleep latency ≤8 minutes with ≥2 SOREMPs, after adequate preparation and an appropriate overnight PSG. [16]
Epworth Sleepiness Scale (ESS): Rates chance of dozing in 8 situations (0-3 each, total 0-24). Score ≥10 suggests excessive daytime sleepiness, but it is a subjective screen—not a diagnosis, a substitute for history/testing, or proof that a patient is safe to drive. [1][3]
Insomnia Severity Index (ISI): Total score: 0-7 normal; 8-14 mild; 15-21 moderate; 22-28 severe. [1]
4. Insomnia Disorder
High Yield — DSM-5 Insomnia Disorder Criteria
"A predominant complaint of dissatisfaction with sleep quantity or quality in addition to DIS (difficulty initiating sleep), DMS (difficulty maintaining sleep), and EMA (early morning awakening). 3 nights per week. At least 3 months. Distress and impairment in functioning. Exclusion criteria." [1]
Breaking this down:
- Subjective complaint — the patient is dissatisfied (this is key; PSG is not required for diagnosis)
- At least one of: Difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), or early morning awakening (EMA) with inability to return to sleep
- Frequency: ≥3 nights per week
- Duration: ≥3 months (this distinguishes chronic insomnia from acute insomnia)
- Functional impairment or significant distress
- Not better explained by another sleep disorder, substance, or inadequate sleep opportunity
"DSM-IV prevalence HK 22.1%, US 22.1%. DSM-5 prevalence 10.8%." [1]
The stricter DSM-5 criteria (requiring 3 months + 3 nights/week) reduce prevalence from ~22% to ~11%.
"By diagnosis – primary, comorbid, or due to other diagnoses. By duration — acute ( < 1 mth), subacute (1-3 mth) or chronic ( > 3 mth). 3P model — predisposing, precipitating, and perpetuating factors." [1]
High Yield — 3P (Spielman) Model of Insomnia
"According to the 3P model, insomnia becomes chronic due to perpetuating factors." [1]
- Predisposing factors: Genetic vulnerability, anxious temperament, female sex, older age, hyperarousal tendency
- Precipitating factors: Life stress, medical illness, bereavement, job loss — triggers acute insomnia
- Perpetuating factors: Maladaptive sleep behaviours (spending too long in bed, napping, clock-watching, irregular schedule), catastrophic cognitions about sleep, conditioned arousal in bed
The model explains why acute insomnia (triggered by a stressor) becomes chronic insomnia — even after the precipitant resolves, the perpetuating factors maintain the problem. This is the rationale for CBT-I targeting perpetuating factors.
"It is difficult to determine whether insomnia is directly caused by the comorbid condition, so the term 'secondary insomnia' should be avoided. For most situations, symptomatic treatment of insomnia is necessary." [1]
This is a key exam point: modern practice uses "comorbid insomnia" rather than "secondary insomnia" because of the bidirectional relationship between insomnia and other conditions (e.g., insomnia worsens depression, depression worsens insomnia). Both should be treated simultaneously.
"Medical disorders, e.g. pain, night sweating, hot flushes, cancer, COAD, parkinsonism. Psychiatric disorders, e.g. major depression, anxiety disorders, substance use, schizophrenia. Sleep disorders, e.g. circadian sleep-wake disorder, obstructive sleep apnea, periodic limb movement disorder." [1]
Exam Trap
Don't automatically assume insomnia in a depressed patient is "just depression." Both insomnia and depression need active treatment. Similarly, a patient with insomnia may have undiagnosed OSA or RLS causing the sleep disturbance — always screen for these.
"The primary treatment goals are: (1) to improve sleep quality and quantity; (2) to improve insomnia related daytime impairments." [1]
High Yield — Treatment of Insomnia: Drug Classes
Prescribed and Approved drugs:
- BZ receptor agonists, e.g. Zopiclone, Zolpidem
- Melatonin receptor agonist, e.g. Ramelteon
- Low dose Doxepin
Off-label drugs:
- Sedative antidepressants, e.g. Remeron (mirtazapine), Trazodone, Paroxetine
- Sedative antipsychotics, e.g. Quetiapine
Drugs with health risks:
- Benzodiazepines, e.g. Lorazepam, Clonazepam
Over-the-counter drugs:
- Promethazine, Melatonin, Valerian [1]
Z-drugs: Zolpidem and Zopiclone
Mechanism: The receptor slide depicts the GABA-A receptor as a pentameric ligand-gated chloride channel. GABA binds between α and β subunits; benzodiazepine-site agonists bind allosterically at an α-γ interface and enhance inhibitory signalling. Zolpidem preferentially binds α1-containing GABA-A receptors, whereas zopiclone is less subtype-selective. The lecture's “BZ1 (α1/α5)” shorthand and claim that both agents lack meaningful motor or anticonvulsant effects are too absolute: both can cause psychomotor impairment, falls, amnesia, tolerance and dependence. [1]
Benzodiazepines generally have a broader GABA-A subtype profile and therefore anxiolytic, muscle-relaxant and anticonvulsant actions in addition to sedation, but neither class should be assumed safe solely from receptor selectivity.
Side effects: Hangover, Daytime sleepiness, Falls, Motor incoordination, Amnesia, Poor memory, Automatism, Sleepwalking. Tolerance, abuse and dependence. [1]
"FDA recent guideline suggested Zolpidem 5mg or Zopiclone 3.75mg for women to avoid daytime sedation and impairment in activities that require alertness." [1]
Current correction: the FDA reduced recommended initial doses for certain zolpidem products because women clear zolpidem more slowly and next-morning blood concentrations may impair driving. The FDA does not regulate zopiclone (which is not marketed in the US); its advice concerns zolpidem and, separately, the US-marketed agent eszopiclone. Use the locally licensed product information and individual patient factors rather than transferring the FDA zolpidem dose statement to zopiclone. [15]
"FDA warning on sleep related complex behavior (sleepwalking, sleep driving)." [1]
The current FDA warning is stronger than the slide implies: eszopiclone, zaleplon and zolpidem carry a boxed warning for rare but serious injuries and deaths from complex sleep behaviours, and are contraindicated after a previous such episode. [14]
| Property | Zolpidem | Zopiclone |
|---|---|---|
| Metabolism | CYP3A4 (60%), CYP2C9 (20%), CYP1A2 (15%) | CYP3A4 (major), CYP2C8 |
| Metabolites | Inactive | One active metabolite (11%) |
| Excretion | 48-67% urine, rest in bile; < 1% active drug in urine | Active metabolite in urine |
| Tmax | 1.6 hrs | Longer than zolpidem |
| T½ | 2.5 hrs | Longer than zolpidem (~5-6h) |
| Drug interactions | CYP3A4 inhibitors (erythromycin → ↑levels) and inducers (phenytoin, St. John's wort → ↓levels) | Same CYP3A4 interactions |
Clinical Safety
Do not prescribe by half-life alone. Before any hypnotic, assess OSA/respiratory risk, alcohol and other CNS depressants, pregnancy, frailty/falls, previous complex sleep behaviour and misuse risk. Use the lowest effective dose for the shortest appropriate duration, review response and deprescribing, and warn explicitly about next-day impairment and driving.
| Component | What It Involves | Why It Works |
|---|---|---|
| Sleep education | Explain sleep physiology, two-process model, sleep hygiene | Corrects misconceptions; empowers patient |
| Stimulus control | Bed only for sleep/sex; leave bed if awake > 15-20 min; fixed wake time | Breaks conditioned arousal association with bed |
| Sleep restriction | Limit time in bed to actual sleep time (e.g., if sleeping 5h, allow only 5h in bed) → gradually increase | Creates mild sleep deprivation → increases homeostatic drive → consolidates sleep |
| Relaxation training | Progressive muscle relaxation, diaphragmatic breathing, guided imagery | Reduces somatic and cognitive hyperarousal |
| Cognitive therapy | Challenge catastrophic thoughts about sleep ("I'll never function if I don't sleep 8 hours") | Reduces cognitive arousal and performance anxiety |
CBT-I is first-line treatment for chronic insomnia. It has durable benefits and can be delivered face-to-face, in groups, by telehealth or through validated digital programmes. “Sleep hygiene” is useful within CBT-I but should not be offered as the sole treatment for chronic insomnia. Sleep restriction can transiently increase sleepiness, so adapt it for people at risk of falls, seizures, bipolar activation or safety-critical driving/work. [12][13]
"Stepped care model (provides least restrictive and costly treatment first) for some common medical conditions, e.g. insomnia." [1]
- Lower-intensity access: validated self-help/digital CBT-I when suitable
- Higher-intensity access: clinician- or therapist-delivered multicomponent CBT-I
- At every level: assess safety and comorbid sleep, medical, psychiatric and substance-related conditions; step up or refer when risk, complexity or non-response requires it
The stepped-care pyramid has two axes: severity (low → high, bottom to top) and volume of patients (high → low, bottom to top). Movement between steps is self-correcting — patients step up if not improved and step down when stable. [11]
Insomnia Treatment Algorithm
The lecture presents a 2008-era treatment algorithm for insomnia disorder [11]:
Do not use the pharmacological branch as a current prescribing ladder. Current guidance places multicomponent CBT-I first. If symptoms remain severe after an adequate CBT-I trial—or CBT-I is temporarily inaccessible—consider medication only after shared decision-making about short-term benefit, harms and deprescribing. Routine escalation to sedating antidepressants, antipsychotics or drug combinations is not supported merely because a previous hypnotic failed; instead, reassess adherence, diagnosis, sleep opportunity, OSA/RLS/circadian disease, substances and psychiatric/medical contributors. [12][13]
5. Hypersomnolence Disorder
"Sleepiness is a normal physiological drive… Differs from feelings of tiredness, fatigue and lack of energy." [1]
This is a critical clinical distinction. Sleepiness = tendency to fall asleep (patient dozes off during activities). Fatigue = lack of energy, weariness (patient feels exhausted but may not actually fall asleep). Sleepiness points to sleep disorders; fatigue has a broader differential (depression, anaemia, hypothyroidism, chronic fatigue syndrome, etc.). [1][3]
"Insufficient sleep, Obstructive sleep apnea syndrome, Narcolepsy, Idiopathic hypersomnolence, Periodic limb movement disorder, Sleep-wake circadian disorder, Medical, psychiatric and substance-use disorders." [1]
The commonest cause is simply insufficient sleep (voluntary sleep restriction in modern society). Always rule this out first.
"An objective measure of sleepiness by asking the patient to try to sleep for 20 min at 2-hour interval starting 2-4 hours after awakening for 4-5 times. Pathological sleepiness: mean sleep latency < 5 min. REM latency – for diagnosis of narcolepsy (presence of at least one sleep onset REM on four naps)." [1]
Current interpretation: an MSLT normally follows an attended overnight PSG and preferably uses five nap opportunities. Narcolepsy requires mean sleep latency ≤8 minutes and ≥2 sleep-onset REM periods (SOREMPs); one SOREMP may come from the preceding nocturnal PSG. Before testing, document adequate regular sleep—ideally with a sleep diary and, where available, actigraphy for two weeks—stabilise treatment of disorders such as OSA, and review REM-modulating or sedating drugs. Medication changes must be supervised because abrupt withdrawal can itself create false-positive REM rebound. [16]
The visual lesson is to calculate from the individual nap rows, not simply label any short latency “narcolepsy”: sleep deprivation, circadian misalignment, untreated OSA and drugs can invalidate the pattern.
High Yield — Narcolepsy: Classic Tetrad
Four characteristic symptoms:
- Excessive sleepiness or sleep attacks
- Cataplexy — sudden loss of bilateral muscle tone provoked by strong emotion. Consciousness remains clear, varies in severity, head drop, facial sagging, jaw drop, slurred speech, buckling of knees, few seconds to minutes
- Sleep paralysis — transient, generalized inability to move or to speak during transition between REM sleep and wakefulness, lasts 1 to several minutes
- Hypnagogic hallucination — vivid perceptual experiences occurring at sleep onset, visual, tactile, kinetic, affect is often fear or dread [1]
Why does narcolepsy produce these symptoms? Narcolepsy Type 1 is caused by loss of orexin (hypocretin)-producing neurons in the lateral hypothalamus (autoimmune destruction, associated with HLA DQB1*0602). Orexin normally stabilises the switch between wake and sleep states. Without it, the brain intrudes into REM inappropriately:
- Sleep attacks = sudden intrusion of sleep into wakefulness
- Cataplexy = REM atonia intruding into wakefulness (triggered by emotion because the amygdala activates the REM-atonia pathway)
- Sleep paralysis = persistence of REM atonia into wakefulness on awakening
- Hypnagogic hallucinations = REM dreaming intruding into the wake-sleep transition
"Type 1 (orexin/hypocretin-1 deficiency and cataplexy). Type 2 (normal orexin/hypocretin level and no cataplexy)." [1]
Current diagnostic logic uses cataplexy with a positive PSG/MSLT pattern, or low CSF hypocretin-1, for type 1; both cataplexy and a measured hypocretin deficiency are not invariably required. Type 2 lacks cataplexy and has normal or unmeasured hypocretin, after excluding mimics. HLA-DQB1*06:02 is supportive epidemiology—not a diagnostic test by itself.
| Feature | Narcolepsy Type 1 | Narcolepsy Type 2 |
|---|---|---|
| Cataplexy | Usually present; low CSF hypocretin can establish type 1 even without clear cataplexy | Absent |
| CSF hypocretin-1 | Low when measured in hypocretin-deficient disease | Normal or not measured |
| HLA DQB1*0602 | Often positive | Variable |
| Pathophysiology | Orexin neuron loss | Unknown |
Diagnosis:
"Diagnosed by overnight polysomnography and MSLT (Short sleep latency < 5 minutes and Sleep onset REM < 20 minutes). HLA DQB10602 allele. CSF hypocretin-1 level."* [1]
Treatment:
"Stimulant drugs (Modafinil, armodafinil, methylphenidate) to suppress daytime sleepiness; Antidepressants for cataplexy; Gamma hydroxybutyrate for both symptoms." [1]
Why antidepressants for cataplexy? SSRIs/SNRIs/TCAs suppress REM sleep → reduce cataplexy, sleep paralysis, and hypnagogic hallucinations (all REM-related phenomena).
"Motor vehicle accidents, Work-related accidents, Impaired neuropsychological function, Impaired motor performance, Reduced quality of life." [1]
Driving Safety
Anyone who is sleepy at the wheel should stop driving and pull over safely; do not drive or operate dangerous machinery until sleepiness is controlled and applicable local licensing rules have been followed. An ESS score, a brief nap or caffeine does not certify fitness to drive. Coffee plus a short nap may be a temporary emergency countermeasure, but it is not treatment and microsleeps may still occur. [19]
6.1 Obstructive Sleep Apnoea Syndrome (OSAS)
High Yield — OSAS Symptoms, Diagnosis, Treatment
Symptoms: Loud and habitual snoring, Intermittent pattern of snoring, Choking/waking up with SOB, Insomnia, Excessive sleep movement, Daytime sleepiness, Dry mouth, Nocturia, Morning headache, Poor concentration and memory. [1]
Lecture-era wording: diagnosed by overnight polysomnography. AHI: 5-15 = mild, 15-30 = moderate, > 30 = severe. [1]
Treatment: CPAP, dental appliance, surgery and positional device (for supine isolated OSA). [1]
Current diagnostic pathway: use attended PSG, or a technically adequate HSAT in an uncomplicated adult with increased risk of moderate-severe OSA. Questionnaires, examination and automated device output alone cannot diagnose OSA. If HSAT is negative, inconclusive or technically inadequate, proceed to PSG; use PSG initially when major cardiorespiratory disease, neuromuscular respiratory weakness, awake hypoventilation, chronic opioid use, stroke history or severe insomnia makes HSAT unsuitable. [17]
Definitions (from supporting notes [3]):
- Apnoea: Complete cessation of oronasal airflow ≥ 10 seconds
- Hypopnoea: ≥ 30% reduction in oronasal flow for ≥ 10 seconds + ≥ 3% oxygen desaturation or EEG arousal
- AHI (Apnoea-Hypopnoea Index): Number of apnoeas + hypopnoeas per hour of EEG-defined sleep. HSAT commonly reports a respiratory event index based on recording time and can therefore underestimate severity when wake time is included.
Risk factors: Male sex (or postmenopausal women), obesity, craniofacial abnormalities (micrognathia, macroglossia, adenotonsillar hypertrophy), endocrine diseases (acromegaly, hypothyroidism), alcohol, smoking, Down's syndrome. [3]
Pathophysiology: During sleep, pharyngeal muscle tone decreases. In OSA, the upper airway collapses (anatomical narrowing + reduced tone) → airflow obstruction → hypoxia + hypercapnia → arousal → airway reopens → patient falls back asleep → cycle repeats → fragmented sleep + intermittent hypoxia.
Why nocturia in OSA? Intrathoracic pressure swings → increased atrial natriuretic peptide (ANP) release → natriuresis.
Why morning headache? CO2 retention during apnoeas → cerebral vasodilation → headache.
Complications: Hypertension (OSA is a recognised secondary cause of HTN), cardiovascular disease, arrhythmias, stroke, metabolic syndrome, accidents. [3]
Interpreting the survival image: the lecture's Kaplan-Meier curves show lower observed survival in the severe-OSA group than in the comparison groups. However, the slide does not display the cohort definition, confidence intervals or adjusted hazard estimates. Do not read exact individual prognoses from the pixels or infer causation from this image alone; use it as evidence that OSA severity and comorbidity deserve active assessment.
Reading the treatment-device slide: the backpack/positioner aims to prevent supine sleep; the mandibular advancement device pulls the jaw and tongue base forward; and nasal CPAP pneumatically splints the upper airway open. PAP treatment should include education, troubleshooting and objective follow-up of efficacy and adherence. Weight management is important where relevant; oral appliances, positional therapy and surgery are selected according to patient preference, OSA phenotype/anatomy and PAP tolerance rather than used interchangeably. [18]
AHI bands (5-14.9, 15-29.9 and ≥30 events/hour) describe event frequency, but treatment decisions also incorporate symptoms, oxygen desaturation burden, arousals, cardiovascular risk, occupation/driving risk and test limitations.
7. Parasomnias
"Any abnormal behavior occurring during sleep. Classify according to the sleep phase parasomnia occurs." [1]
Parasomnias are classified by the sleep phase in which they occur: sleep-wake transition, NREM, or REM [11].
High Yield — NREM vs REM Parasomnia Differentiation
| Feature | NREM Parasomnia | REM Parasomnia |
|---|---|---|
| Timing | First half of the night | Later half of the night |
| Recall | Unable to recall behavior | Partial recall of behavior or dream content |
| Dream relation | Unrelated to dreams | Acting out of dream content |
| Examples | Sleepwalking, sleep terrors, sleep-related eating disorder | RBD, sleep paralysis, nightmares |
7.1 NREM Parasomnias
"Incomplete transition from deep sleep to wake. Talking, hand movement, standing and walking, urinating, eating. Neurodevelopmental disorder: peak age of onset 7 yrs old. Precipitating factors: physical exertion, heavy exercise, fever, drugs, OSAS, PLMD." [1]
"Treatment: Accident prevention, Treat the precipitating factors (e.g., OSAS), Drug treatment: clonazepam." [1]
Why does sleepwalking peak in childhood? Children have the most SWS (NREM 3/4) → more opportunities for incomplete arousal from deep sleep. It usually resolves with maturation.
Current practice: first secure the environment (lock exits/windows, remove weapons and trip hazards, protect stairs), regularise sleep and treat triggers such as sleep deprivation, alcohol, OSA or provoking medication. Clonazepam is not routine first-line therapy; reserve medication for frequent, dangerous or refractory episodes after diagnostic review, especially because sedation, falls and worsening sleep-disordered breathing may outweigh benefit.
"Eating food with resultant increased weight. Treatment: SSRIs, topiramate, clonazepam." [1]
This drug list is lecture-era material, not an automatic sequence. Confirm that episodes are involuntary sleep-related eating rather than waking binge-eating or nocturnal eating syndrome, remove hazardous foods/objects, review culprit medicines and treat comorbid sleep disorders before specialist pharmacotherapy.
The lecture provides a useful comparison table of sleepwalking vs. SRED [1]:
| Feature | Sleepwalking | SRED |
|---|---|---|
| Age at onset | Childhood | Middle age |
| Trigger factor | Uncommon (19%) | Common (62%) |
| Nightly episodes | Uncommon (10%) | Common (73%) |
| Total loss of awareness | Common (39%) | Rare (7%) |
| Dream-like mentation | Common (67%) | Rare (0%) |
| Injuries | Common (52%) | Rare (7%) |
| History of eating disorder | Uncommon (14%) | Common (60%) |
| Current insomnia | Rare (5%) | Common (73%) |
| Psychiatric disorders | Uncommon (21%) | Common (62%) |
7.2 REM Parasomnias
High Yield — RBD and Neurodegeneration Risk
"Clinical features: Frequent vivid, action-packed, violent dream; loss of muscle atonia that results in enactment of dream content. 50% of cases are associated with neurological conditions: organic lesions at brain stem area, other neurodegenerative disorders which affect REM sleep control. High future risk of neurodegenerative disorders. OSA can precipitate RBD. Treatment: Clonazepam." [1]
Why is RBD so important? In normal REM sleep, the brainstem actively inhibits motor neurons (muscle atonia) so you don't act out your dreams. In RBD, this atonia mechanism fails. The patient punches, kicks, or leaps out of bed during vivid dreams — often injuring themselves or bed partners.
The clinical photograph demonstrates the key hazard: vigorous dream enactment can propel a patient from bed or injure a partner. Diagnosis requires a compatible history plus video-PSG evidence of REM sleep without atonia; untreated OSA can mimic dream enactment (“pseudo-RBD”), so it should not simply be labelled a precipitant.
The neurodegenerative link is critical: isolated RBD is a strong prodromal marker of α-synucleinopathies (Parkinson disease, dementia with Lewy bodies and multiple system atrophy). The long-term conversion risk is substantial but varies with cohort and follow-up; avoid presenting a fixed percentage/timeline as an individual certainty. Arrange longitudinal neurological review and counsel sensitively. [20]
Management begins with injury prevention: pad the floor, remove weapons/sharp furniture, consider separate sleeping arrangements during violent episodes and treat mimics. Current AASM guidance conditionally supports immediate-release melatonin or clonazepam for isolated RBD after individualised risk-benefit review. Clonazepam may worsen OSA and increase falls or cognitive adverse effects, particularly in older adults. [20]
"Awakening from REM with muscle atonia → 'ghost oppression'. Clear sensorium, difficulty in breathing, acute anxiety, hypnagogic imagery. Mostly isolated. Precipitating factor: sleep deprivation, irregular sleep habits, overtiredness, stress. More frequent sleep paralysis is either familial or associated with narcolepsy. Tx: TCAs and SSRIs which suppress REM sleep." [1]
Why "ghost oppression"? In Chinese culture (鬼壓床), the experience of paralysis with fear and visual hallucinations during the transition from sleep to wake is culturally interpreted as a supernatural attack. Understanding the REM-based mechanism allows reassurance.
For isolated episodes, reassurance, adequate regular sleep and trigger reduction are usually sufficient. Recurrent distressing episodes require assessment for narcolepsy and other sleep disorders; REM-suppressing antidepressants are not routine first-line treatment for occasional isolated sleep paralysis.
"Mental activity during sleep. Most dreams occur in REM sleep. Function – organization of memory." [1]
"Drugs that increase dreaming include: beta-blockers (atenolol, propranolol), antidepressants (SSRIs, SNRIs), antipsychotics (Risperidone), GABA agonists (gabapentin, zopiclone, BZs), anticholinesterase inhibitors (donepezil, rivastigmine), and dopamine agonists (L-dopa)." [1]
Treatment of nightmares:
"Recommended treatment of PTSD-associated nightmares and nightmare disorder — image rehearsal therapy. Treatment of PTSD-associated nightmare (second line): atypical antipsychotics, clonidine, gabapentin, prazosin. Treatment of nightmare disorder (second line): prazosin, nitrazepam, triazolam." [1]
Prazosin (alpha-1 adrenergic blocker) is a classic exam answer for PTSD-related nightmares. It reduces noradrenergic activation during sleep, decreasing nightmare frequency and intensity.
Current framing: imagery rehearsal therapy remains the principal behavioural treatment. Prazosin may be considered for PTSD-associated nightmares after individual assessment, but the older slide's antipsychotic and benzodiazepine lists are not routine treatment ladders; address PTSD itself, falls/hypotension, substance use and OSA before adding medication.
8.1 Restless Leg Syndrome (RLS) / Periodic Limb Movement Disorder (PLMD)
High Yield — RLS/PLMD
"An urge to move one's legs which is often accompanied by an unpleasant sensation. 80-90% will have PLMD which is a common cause of insomnia and excessive daytime sleepiness first diagnosed during sleep study — characterized by periodic episodes of repetitive and highly stereotyped limb movements during sleep, causes repeated arousal. Sequence of 4 or more LMs separated by at least 5 sec and not more than 90 sec." [1]
"2 phenotypes of RLS — 1. early-onset, familial or idiopathic RLS (more common); 2. late-onset, sporadic or secondary RLS — iron deficiency anemia, renal failure, neuropathy." [1]
"RLS worsens during rest and at night." [1]
"Ferritin level — iron supplement indicated when ferritin < 75 µg/L (Fe sulphate 325mg bd on an empty stomach)." [1]
"RLS diagnosis based on history. PLMD diagnosed by overnight polysomnography." [1]
"Treatment — alpha-2-delta ligands (gabapentin, pregabalin), dopamine agonists (L-dopa, pramipexole, ropinirole), opioids (oxycodone), clonazepam." [1]
RLS diagnostic criteria (IRLSSG): The urge to move the legs must:
- Begin or worsen during periods of rest/inactivity
- Be partially or totally relieved by movement
- Occur exclusively or predominantly in the evening/night
- Not be solely accounted for by another medical/behavioural condition
Current iron approach: obtain a morning iron panel including ferritin and transferrin saturation, ideally avoiding iron-containing supplements/foods beforehand. AASM consensus thresholds support oral or IV iron when ferritin is ≤75 ng/mL or transferrin saturation < 20%, with route and formulation individualised; inflammation can make ferritin misleading. The slide's fixed ferrous-sulphate dose and “empty stomach” instruction should not be prescribed blindly—consider tolerability, absorption, interactions, contraindications and follow-up indices. [21]
Alpha-2-delta ligands (gabapentin, gabapentin enacarbil or pregabalin) now have strong AASM recommendations for adults with RLS. Routine long-term dopamine agonist use is discouraged because of augmentation—symptoms begin earlier, intensify, shorten their rest latency or spread to other body regions. Opioids are reserved for selected refractory disease under specialist risk controls; clonazepam is not routine disease-directed therapy. First also address exacerbating alcohol/caffeine, antihistaminergic/serotonergic/antidopaminergic drugs and untreated OSA. [21]
High Yield — CRSWD: Delayed Sleep-Wake Phase Disorder
"The most common type of CRSWD is delayed SWPD (DSWPD) — 80% of all CRSWD cases, followed by advanced SWPD, non-24 hr SWPD, and irregular SWPD. DSWPD is more common in adolescents and young adults." [1]
"Sleep diary, actigraphy, chronotype questionnaire, salivary dim light melatonin onset (DLMO)." [1]
"Low dose melatonin (0.5 mg) 5 hr before habitual sleep onset or 2-4 hr before DLMO. Evening light restriction and 2 hr of bright light therapy (10000 lux) on awakening." [1]
| Type | Who Gets It | Sleep Pattern | Treatment |
|---|---|---|---|
| Delayed SWPD | Adolescents, young adults | Sleep onset very late (e.g. 3-4 am), wake late (e.g. 11 am-noon); normal quality when allowed to sleep at preferred time | Low-dose melatonin before DLMO; morning bright light; evening light restriction |
| Advanced SWPD | Elderly | Sleep onset very early (e.g. 7-8 pm), wake very early (e.g. 3-4 am) | Evening bright light; morning light restriction |
| Non-24h SWPD | Blind individuals | Free-running clock (sleep onset drifts later each day) | Melatonin, tasimelteon |
| Irregular SWPD | Dementia, brain injury | No consolidated sleep period; sleep scattered across 24h | Structured zeitgebers, melatonin, bright light |
The slide provides an example regimen, not a universal prescription. Direction, timing, intensity and duration of melatonin/light determine whether the clock advances or delays and should be anchored to the patient's sleep diary/actigraphy and, where available, DLMO. Screen for ocular/light-sensitive conditions and monitor for mood activation in bipolar disorder.
9.1 General Approaches for Reversing Sleepiness
"Regular and adequate sleep. Caffeine (200 mg or 2-3 cups) not later than 4 pm. Short naps (15 min). Bright light therapy (10000 lux for 30 min) for shift work, jet lag, seasonal affective disorder. Nature of shift work (forward shift is better — easier to delay sleep, regular night shift, 12-hour 2-shift). Nasal CPAP, surgery, and dental appliance (OSAS). Modafinil and CNS stimulants (narcolepsy)." [1]
These measures are diagnosis-specific and do not override the driving warning above. In particular, caffeine, bright light or a brief nap may transiently improve alertness but should never be used to justify continuing to drive while sleepy.
Why forward shift rotation? It is easier to delay your circadian clock (stay up later) than to advance it (go to bed earlier). Rotating shifts in a clockwise direction (morning → evening → night) is less disruptive than anti-clockwise.
10. Exam Intelligence
| Trap | Why It's Wrong | Correct Answer |
|---|---|---|
| Calling all insomnia "secondary" when a comorbid condition exists | Bidirectional relationship; "secondary" implies causality that is usually unproven | Use "comorbid insomnia"; treat both conditions |
| Diagnosing narcolepsy without cataplexy as Type 1 | Type 1 requires cataplexy OR low CSF hypocretin-1 | Without cataplexy and with normal hypocretin → Type 2 |
| Using PSG to diagnose uncomplicated chronic insomnia | Insomnia is diagnosed clinically; routine PSG is unnecessary | Use PSG when another disorder or atypical/dangerous behaviour is suspected; narcolepsy needs PSG followed by MSLT |
| Recommending hypnotics first-line for chronic insomnia | Z-drugs and BZs can cause next-day impairment, falls, complex sleep behaviours and dependence | Multicomponent CBT-I first; medication only after individual shared decision and review |
| Treating first-half vs second-half timing as diagnostic | Timing is only a tendency and events can overlap | Combine timing with recall, dream enactment, semiology and video-PSG when indicated |
| Using a standard anaemia ferritin threshold alone for RLS | Neurological iron thresholds differ and ferritin may be confounded by inflammation | Check ferritin and transferrin saturation; consider iron at ferritin ≤75 ng/mL or TSAT < 20% with individualised route |
| Confusing sleepiness with fatigue | Sleepiness = tendency to doze; fatigue = lack of energy | Different differential diagnoses and management |
| Missing RBD as a prodromal marker—or diagnosing it from history alone | OSA and other disorders can mimic dream enactment | Confirm REM sleep without atonia on video-PSG, ensure bedroom safety and arrange longitudinal follow-up |
Depression classically shows: shortened REM latency (< 90 min), increased REM density, decreased SWS. This is contrasted with the 2023 MCQ Q75, which asked the most suggestive symptom of depression over GAD — the answer was weight gain (D), since difficulty falling asleep, loss of concentration, and muscle tension overlap significantly with GAD. [5]
- CFB PSY02 classifies sleep-wake disorders within DSM-5 under: Insomnia disorder, Hypersomnolence/Narcolepsy, Breathing-related, Circadian rhythm, Parasomnias, RLS/PLMD, Substance/medication-induced. [4]
- GC 024 (A Fatigued and Sleepy Patient) overlaps with this lecture in differential diagnosis of sleepiness and approach to the sleepy patient. Ensure you can differentiate sleepiness from fatigue.
- GC 081 (Seizure and LOC) is relevant because EEG is used in both epilepsy and sleep medicine (sleep staging requires EEG), and nocturnal seizures must be differentiated from parasomnias.
- OSA as a secondary cause of hypertension is a common exam point across multiple lectures. [9]
- AOS Psychiatry notes that sleeping pills and BZDs will not be used in long-term management — examiners may test this. [10]
High Yield Summary
-
Sleep physiology
- Two-process model (Process C = circadian/SCN; Process S = homeostatic/adenosine). Current stages are N1, N2, N3 and REM; early-night N3 and later, longer REM bouts are tendencies visible on the hypnogram.
-
Insomnia Disorder (DSM-5)
- DIS/DMS/EMA + ≥3 nights/week + ≥3 months + distress/impairment. The 3P model explains chronification. Multicomponent CBT-I is first-line; sleep hygiene alone is insufficient. Hypnotics require short-duration, individualised risk-benefit review and driving/complex-behaviour counselling.
-
Narcolepsy
- Tetrad = sleepiness + cataplexy + sleep paralysis + hypnagogic hallucinations. Type 1 is established by cataplexy with the characteristic PSG/MSLT pattern or low CSF hypocretin. Prepared PSG + MSLT: mean latency ≤8 min and ≥2 SOREMPs.
-
OSAS
- AHI grading: 5-14.9 mild, 15-29.9 moderate, ≥30 severe. Diagnose with PSG or suitable HSAT; negative/inadequate HSAT requires PSG. PAP is central therapy, with weight management and selected oral, positional or surgical options.
-
Parasomnias
- NREM events usually arise earlier with limited recall; REM events are usually later with dream recall, but timing is not diagnostic. RBD requires video-PSG REM without atonia; prioritise bedroom safety, assess OSA mimics and individualise melatonin/clonazepam.
-
RLS/PLMD
- Urge to move legs, worse at rest/night and relieved by movement. Check ferritin + transferrin saturation and replace iron when indicated. Alpha-2-delta ligands are preferred; avoid routine dopamine agonists because of augmentation.
-
CRSWD
- DSWPD is common in adolescents/young adults. Melatonin, morning light and evening light restriction must be phase-timed to the individual's rhythm rather than used as a universal clock-time recipe.
Active Recall - Lecture Notes
[1] Lecture slides: GC 165. I can't fall asleep Sleep physiology and Sleep disorders.pdf [2] Senior notes: Ryan Ho Psychiatry.pdf (Section 9.2 Sleep Disorders) [3] Senior notes: Maksim Medicine Notes.pdf (Section 12.9 Sleep-related breathing disorders); Ryan Ho Respiratory.pdf (Section 3.8) [4] Lecture slides: CFB (PSY02) Classification and Diagnosis of Psychiatric Illness.pdf (Sleep-wake disorders slide) [5] Past papers: 2023 Fourth Summative MCQ.pdf (Q75) [9] Senior notes: Block A - High blood pressure_ hypertension.pdf [10] AOS material: AOS - Psych.md [11] Lecture slides: GC 165. I can’t fall asleep Sleep physiology and Sleep disorders.pdf [12] American College of Physicians. ACP recommends cognitive behavioral therapy as initial treatment for chronic insomnia. [13] American Academy of Sleep Medicine. Behavioral and psychological treatments for chronic insomnia disorder in adults: clinical practice guideline. [14] US Food and Drug Administration. Boxed warning for serious injuries caused by complex sleep behaviours with certain insomnia medicines. [15] US Food and Drug Administration. Risk of next-morning impairment after zolpidem and lower recommended doses. [16] American Academy of Sleep Medicine. Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults. [17] American Academy of Sleep Medicine. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea. [18] American Academy of Sleep Medicine. Treatment of adult obstructive sleep apnea with positive airway pressure: clinical practice guideline. [19] US National Highway Traffic Safety Administration. Drowsy driving. [20] American Academy of Sleep Medicine. Management of REM sleep behavior disorder: clinical practice guideline. [21] American Academy of Sleep Medicine. Treatment of restless legs syndrome and periodic limb movement disorder: clinical practice guideline.
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