Insomnia Flashcards
Physiological sleep-wake cycle
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
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
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
Which stages of NERM sleep does BZD interfere with?
BZD increases stage 2 (deep sleep), but decreases stages 3 and 4 (restorative sleep)
Sleep assessment
Objective:
- Polysomnography (i.e. comprehensive recording of EEG, SpO2, RR, HR)
Subjective:
- Quality of sleep
- Excessive daytime sleepiness
How much sleep is enough/recommended?
at least 7h per day
<6h a/w adverse health outcomes: DM, HTN, obesity, heart disease, stroke, depression, impaired immunity, risks of accidents/deaths
Define insomnia disorder
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
Insomnia disorder classifications with duration
Episode - lasting 1 month to less than 3 months
Persistent - lasting 3 months or more
Recurrent - experience 2 or more episodes within 1 year
General management of insomnia disorder
- Identify and manage underlying causes/disorders/stressors
- Sleep hygiene
- Psychotherapy (e.g., CBT)
- PRN sleeping pills when appropriate
‘Symptom’: Acute insomnia
- Definition
- Duration
- Likely cause
- Management
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)
‘Symptom’: Chronic insomnia
- Definition
- Duration
- Likely cause
- Management
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
[Non-pharmacological for Insomnia]
*Mainstays, pharmacological are adjunct
Behavioral interventions:
- CBT
- Relaxation training
- Sleep restriction therapy
- Stimulus control therapy
- Sleep hygiene
[Non-pharmacological for Insomnia]
Counsel sleep hygiene
- 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)
[Pharmacological for Insomnia]
What is used?
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
[Pharmacological for Insomnia]
Anxiolytics VS Hypnotics VS Antipsychotics
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
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- MOA
Potentiates GABA, relieves anxiety and insomnia
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Use in insomnia
NOT used as monotherapy, adjunct to antidepressants for MDD or anxiety disorders
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- SEs
- 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)
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Onset
Quick onset for “physical/somatic” symptoms (insomnia and tension)
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Duration
- How to reduce risk of dependence
- 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)
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Contraindications
- Hypersensitivity to benzodiazepines or any component of the product
- Acute narrow-angle glaucoma
- Persons with history of substance abuse
ONLY for Parental route (IV & IM):
- Hypersensitivity to excipients: polyethylene glycol, propylene glycol, or benzyl alcohol (Solvent used in majority of Lorazepam parental formulation)
- 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
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Which BZD should be avoided in elderly
Avoid Diazepam (long-acting) in elderly due to long half-life, cause drowsiness, affect cognition, increase risk of falls
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Discontinuation
Gradually taper off if BZD has been used daily for weeks/months, to avoid rebound anxiety or withdrawal seizures
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Withdrawal symptoms (when abruptly discontinued)
Sweating, increased HR, tremors, insomnia, agitation, hallucinations, rebound anxiety, seizures
[Pharmacological for Insomnia - HYPNOTICS BENZODIAZEPINE]
- Lorazepam dose for insomnia
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
[Pharmacological for Insomnia - Z-HYPNOTICS]
- MOA
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
[Pharmacological for Insomnia - Z-HYPNOTICS]
- Use
Relieve insomnia, NOT anxiety (does not relax muscles)
[Pharmacological for Insomnia - Z-HYPNOTICS]
- SE
- 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
[Pharmacological for Insomnia - Z-HYPNOTICS]
- Examples
- Zolpidem (females should be given half dose due to slower metabolism)
- Zopiclone
[Pharmacological for Insomnia - Z-HYPNOTICS]
- Cautions
Similar to BZDs:
- risk of dependence and high abuse potential
- may also cause respiratory depression and death (avoid with opioids - increased mortality)
[Pharmacological for Insomnia - ANTIHISTAMINES]
- SEs
- Sedation
- Anticholinergic effects (caution in elderly)
Acute urinary retention and delirium are medical emergencies
[Pharmacological for Insomnia - ANTIHISTAMINES]
- Cautions
Caution in:
- Prostatic hypertrophy
- Urinary retention
- Pyloroduodenal obstruction
- Angle-closure glaucoma
- Epilepsy
- QTc interval prolongation (with Hydroxyzine)
- Coronary artery disease (with Promethazine)
[Pharmacological for Insomnia - ANTIHISTAMINES]
- Risk of dependence
Low risk of dependence and abuse
[Pharmacological for Insomnia - Melatonin receptor agonist]
- MOA
MT1 and MT2 agonist, relieves insomnia
[Pharmacological for Insomnia - Melatonin receptor agonist]
- SE
Generally well-tolerated, some headache
[Pharmacological for Insomnia - Melatonin receptor agonist]
- Use
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
[Pharmacological for Insomnia - Lemborexant]
- MOA
OX1 and OX2 orexin receptor antagonist
[Pharmacological for Insomnia - Lemborexant]
- SE
Somnolence, nightmares
Uncommon: sleep paralysis, cataplexy-like symptoms
[Pharmacological for Insomnia - Lemborexant]
Risk of dependence
Lower risk of tolerance and dependence compared with BZDs
[Pharmacological for Insomnia - Lemborexant]
- Contraindications
Contraindicated in:
- Narcolepsy (excessive daytime sleepiness, loss of orexin neurons)
- Severe hepatic impairment
- Concurrent use with moderate-strong CYP3A4 inhibitors/inducers
[Pharmacological for Insomnia - off-label hypnotics (ANTIDEPRESSANTS)]
- MOA
- SE
- Dose
- Risk of dependence
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
[Pharmacological for Insomnia - off-label hypnotics (ANTIPSYCHOTICS)]
- MOA
- SE
- Dose
- Risk of dependence
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
