Insomnia Flashcards

1
Q

Physiological sleep-wake cycle

A

24h

  • Resetting of internal clock by cues (day light)
  • Hormone - melatonin secretion increased during sleep, suppressed by bright light
  • Neurotransmitters:

Sleep-promoting: GABA
Wakefulness-promoting: NE, DA, acetylcholine, histamine, orexin

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2
Q

Normal sleep architecture

States:

  • Wakefulness
  • Non-rapid eye movement (NREM) sleep
  • Rapid eye movement (REM) sleep
  • Cyclical: 4-6 cycles per night, 70-120min/cycle
A

NREM: 75% of total sleep, low HR, RR, BP

  • Stage 1: light sleep
  • Stage 2: deep sleep
  • Stage 3 and 4: delta sleep, restorative sleep (release growth hormones, restores protein synthesis, wound healing, immune function)

REM: 25% of total sleep

  • a/w dreaming, memory consolidation
  • HR, RR, BP can fluctuate and become irregular
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3
Q

Which stages of NERM sleep does BZD interfere with?

A

BZD increases stage 2 (deep sleep), but decreases stages 3 and 4 (restorative sleep)

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4
Q

Sleep assessment

A

Objective:

  • Polysomnography (i.e. comprehensive recording of EEG, SpO2, RR, HR)

Subjective:

  • Quality of sleep
  • Excessive daytime sleepiness
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5
Q

How much sleep is enough/recommended?

A

at least 7h per day

<6h a/w adverse health outcomes: DM, HTN, obesity, heart disease, stroke, depression, impaired immunity, risks of accidents/deaths

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6
Q

Define insomnia disorder

A

Inability to initiate/maintain sleep, a/w daytime problems of fatigue, impaired concentration, memory etc.

A. Primary complain of unsatisfying sleep quantity or quality with the presence of 1 or more of the following:

  • Difficulty w sleep initiation
  • Difficulty with sleep maintenance
  • Early-morning awakening

B. Sleep complaint is a/w social, occupational, academic, educational, behavioral, or functional distress or impairment

C. Sleep complaint occurs at least 3 nights per week and has been present for at least 3 months

D. Sleep difficulties despite ample opportunity to sleep

E. Sleep complaint is not attributed to or explained by another sleep-wake disorder, the adverse effect of a medication or substance, or a coexisting psychiatric illness or medical condition

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7
Q

Insomnia disorder classifications with duration

A

Episode - lasting 1 month to less than 3 months
Persistent - lasting 3 months or more
Recurrent - experience 2 or more episodes within 1 year

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8
Q

General management of insomnia disorder

A
  • Identify and manage underlying causes/disorders/stressors
  • Sleep hygiene
  • Psychotherapy (e.g., CBT)
  • PRN sleeping pills when appropriate
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9
Q

‘Symptom’: Acute insomnia

  • Definition
  • Duration
  • Likely cause
  • Management
A

Sleep difficulties for 1 night to few weeks

Transient <1 week
Short-term <4 weeks

Likely cause: acute stressors

Management:

  • Transient: Sleep hygiene
  • Short-term: Sleep hygiene, PRN short course hypnotic may be considered for 7-10 days (up 2-4 weeks)
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10
Q

‘Symptom’: Chronic insomnia

  • Definition
  • Duration
  • Likely cause
  • Management
A

Sleep difficulties for >=3 nights per week, for >=1 month

Duration >4 weeks

Likely cause:

  • Secondary to underlying psychiatric and/or medical problems
  • Poor sleep hygiene
  • Substance abuse
  • Primary sleep disorder (sleep apnea, restless legs syndrome)

Management:

  • Investigate and manage underlying causes/conditions
  • Sleep hygiene
  • Discourage long-term use of hypnotics
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11
Q

[Non-pharmacological for Insomnia]

*Mainstays, pharmacological are adjunct

A

Behavioral interventions:

  • CBT
  • Relaxation training
  • Sleep restriction therapy
  • Stimulus control therapy
  • Sleep hygiene
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12
Q

[Non-pharmacological for Insomnia]

Counsel sleep hygiene

A
  • Avoid caffeine, nicotine, alcohol in the later part of the day
  • Avoid heavy meals within 2h of bedtime
  • Avoid drinking fluids after dinner to prevent frequent night-time urination
  • Avoid environments that will make you active after 5pm
  • Only use bed to sleep, sit in chair if want to relax
  • Avoid watching TV in bed
  • Establish a routine for getting ready to go to bed
  • Set time aside to relax before bed, relaxation techniques
  • Create conducive sleep environment (comfortable temperature, no noise, darker room)
  • When in bed, relax and think pleasant thoughts
  • Get up at the same time every day, including weekends
  • Avoid taking daytime naps, if must, take before 3pm and do not exceed 1h
  • Pursue regular physical activities, but avoid vigorous activity before bedtime (after 5pm)
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13
Q

[Pharmacological for Insomnia]

What is used?

A

Fast-acting anxiolytics/sedatives/hypnotics used as adjuncts for short-term relief of distressful insomnia/anxiety, and limited to PRN dosing, at lowest effective dose, and short-course (1-2 weeks)

  • BZD (Diazepam, Lorazepam only)
  • Z-Hypnotics (Zolpidem, Zopiclone)
  • Antihistamine (Hydroxyzine or Promethazine)
  • Melatonin receptor agonist
  • Lemborexant
  • Off-label: Trazadone (antidepressant)
  • Off-label: Antipsychotics

Only BZD and Hydroxyzine can be used as anxiolytics as well

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14
Q

[Pharmacological for Insomnia]

Anxiolytics VS Hypnotics VS Antipsychotics

A

Anxiolytics (sedative)

  • induces sleep when given at night

Hypnotics (sleeping pills)

  • sedate when given in the day

Antipsychotics

  • tranquilize without impairment of consciousness
  • does not cause paradoxical excitement
  • used to calm disturbed patients in the short-term
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15
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • MOA
A

Potentiates GABA, relieves anxiety and insomnia

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16
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Use in insomnia
A

NOT used as monotherapy, adjunct to antidepressants for MDD or anxiety disorders

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17
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • SEs
A
  • GI: N/V, constipation
  • Sedation, drowsiness
  • Muscle weakness, ataxia
  • Amnesia

(less common)

  • hallucinations (abnormal thinking, changes in behaviour, or hearing or seeing things)
  • slurred speech
  • vertigo, headache
  • confusion
  • paradoxical excitement/disinhibition
  • unusual sleep-related activities
  • fast, slow or irregular heartbeat
  • problems with eyesight
  • dark brown urine, light coloured stools (pale grey/clay-coloured), yellowing of skin and eyes (symptoms of liver problems)
18
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Onset
A

Quick onset for “physical/somatic” symptoms (insomnia and tension)

19
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Duration
  • How to reduce risk of dependence
A
  • Short term (1-2 weeks) to minimize risk for dependence
  • Short to intermediate acting BZDs
  • Lowest effective dose
  • Intermittently, avoid taking regularly (take once every 2 or 3 nights, if required consider alternative with antihistamines)
20
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Contraindications
A
  1. Hypersensitivity to benzodiazepines or any component of the product
  2. Acute narrow-angle glaucoma
  3. Persons with history of substance abuse

ONLY for Parental route (IV & IM):

  1. Hypersensitivity to excipients: polyethylene glycol, propylene glycol, or benzyl alcohol (Solvent used in majority of Lorazepam parental formulation)
  2. Severe respiratory insufficiency (except during mechanical ventilation) - e.g., avoid in obstructive sleep apnea, COPD, acute asthma due to risk of respiratory depression; also include unstable myasthenia gravis as intercostal muscle cannot work properly to expand lung

Need to standby antidote (Flumazenil) for parenteral benzodiazepine use

21
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Which BZD should be avoided in elderly
A

Avoid Diazepam (long-acting) in elderly due to long half-life, cause drowsiness, affect cognition, increase risk of falls

22
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Discontinuation
A

Gradually taper off if BZD has been used daily for weeks/months, to avoid rebound anxiety or withdrawal seizures

23
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Withdrawal symptoms (when abruptly discontinued)
A

Sweating, increased HR, tremors, insomnia, agitation, hallucinations, rebound anxiety, seizures

24
Q

[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]

  • Lorazepam dose for insomnia
A

PO 1-2mg at bedtime (2-4mg)

May start at 0.5mg - smallest tablet

Also note that the IV/IM 2mg/ml formulation is listed as an exemption drug in Singapore, requires standby Flumazenil if used

25
Q

[Pharmacological for Insomnia - Z-HYPNOTICS]

  • MOA
A

Preferentially binds to BZD binding site with gamma and alpha-1 subunits, therefore causing sedation, but no anxiolytic effects

FYI: at higher doses, may be less specific to this binding site, possibly have anxiolytics and relaxation effects as well

26
Q

[Pharmacological for Insomnia - Z-HYPNOTICS]

  • Use
A

Relieve insomnia, NOT anxiety (does not relax muscles)

27
Q

[Pharmacological for Insomnia - Z-HYPNOTICS]

  • SE
A
  • Taste disturbances (Zopiclone has a metallic taste)
  • Less common: nausea, vomiting, dizziness, drowsiness, dry mouth, headache, complex sleep behaviors (sleepwalking), rarely amnesia, confusion, hallucinations, nightmares, muscle weakness, fast/strong/irregular heartbeat
  • Dependence
28
Q

[Pharmacological for Insomnia - Z-HYPNOTICS]

  • Examples
A
  • Zolpidem (females should be given half dose due to slower metabolism)
  • Zopiclone
29
Q

[Pharmacological for Insomnia - Z-HYPNOTICS]

  • Cautions
A

Similar to BZDs:

  • risk of dependence and high abuse potential
  • may also cause respiratory depression and death (avoid with opioids - increased mortality)
30
Q

[Pharmacological for Insomnia - ANTIHISTAMINES]

  • SEs
A
  • Sedation
  • Anticholinergic effects (caution in elderly)

Acute urinary retention and delirium are medical emergencies

31
Q

[Pharmacological for Insomnia - ANTIHISTAMINES]

  • Cautions
A

Caution in:

  • Prostatic hypertrophy
  • Urinary retention
  • Pyloroduodenal obstruction
  • Angle-closure glaucoma
  • Epilepsy
  • QTc interval prolongation (with Hydroxyzine)
  • Coronary artery disease (with Promethazine)
32
Q

[Pharmacological for Insomnia - ANTIHISTAMINES]

  • Risk of dependence
A

Low risk of dependence and abuse

33
Q

[Pharmacological for Insomnia - Melatonin receptor agonist]

  • MOA
A

MT1 and MT2 agonist, relieves insomnia

34
Q

[Pharmacological for Insomnia - Melatonin receptor agonist]

  • SE
A

Generally well-tolerated, some headache

35
Q

[Pharmacological for Insomnia - Melatonin receptor agonist]

  • Use
A

May be preferred for adults >55y

  • Generally well-tolerated, safe
  • But not that effective
  • Helps to correct melatonin hormone level, regulate diurnal sleep-wake cycle
  • Give 1-2h before bedtime, after food

Brand name: Circadin, prolonged release

36
Q

[Pharmacological for Insomnia - Lemborexant]

  • MOA
A

OX1 and OX2 orexin receptor antagonist

37
Q

[Pharmacological for Insomnia - Lemborexant]

  • SE
A

Somnolence, nightmares

Uncommon: sleep paralysis, cataplexy-like symptoms

38
Q

[Pharmacological for Insomnia - Lemborexant]

Risk of dependence

A

Lower risk of tolerance and dependence compared with BZDs

39
Q

[Pharmacological for Insomnia - Lemborexant]

  • Contraindications
A

Contraindicated in:

  • Narcolepsy (excessive daytime sleepiness, loss of orexin neurons)
  • Severe hepatic impairment
  • Concurrent use with moderate-strong CYP3A4 inhibitors/inducers
40
Q

[Pharmacological for Insomnia - off-label hypnotics (ANTIDEPRESSANTS)]

  • MOA
  • SE
  • Dose
  • Risk of dependence
A

Trazodone (SARI)

  • MOA: inhibit 5HT reuptake, antagonize 5HT2A, H1, a1 receptors
  • Side Effects:

GI - N/V/D [5HT3 agonism]
Sexual dysfunction [5HT2 agonism]

Sedation [H1 antagonism]
Orthostatic hypotension [a1 adrenoceptor antagonism]

Rare: priapism

  • Dose: low doses 25-50mg PRN for insomnia
  • Low risk of dependence and abuse
41
Q

[Pharmacological for Insomnia - off-label hypnotics (ANTIPSYCHOTICS)]

  • MOA
  • SE
  • Dose
  • Risk of dependence
A

E.g., Quetiapine

  • MOA: D2 antagonism, H1 antagonism
  • SE: sedation, EPSE, metabolic SE (weight gain, diabetes)
  • Typically not used due to antipsychotic SEs
  • Low dose PRN
  • Reserved for agitated behaviors in acute psychosis
  • Low risk of dependence