Sleep Disturbance

Overview                           

Sleep disturbance is common in patients with chronic disease and is often multifactorial. Treat if sleep disturbance is impacting the patient’s quality of life and daily functioning. Provide patient and family education and counseling regarding realistic expectations in the treatment of sleep disturbance. Discuss goals of care and balance burden of treatment with likely benefit in accordance with the patient’s wishes, values, and priorities.

  • Assess for sleep disturbance with validated tools 
  • Consider non-pharmacological interventions before pharmacological therapy
  1. Poorly controlled symptoms or disease complications (e.g. pain, breathlessness, pruritus, restless legs syndrome, ascites - see Patient Sleep Handout)
  2. Consider hepatic encephalopathy in any patient with cirrhosis and excessive daytime sleepiness
  3. Consider opioid excess for patients on opioid therapy experiencing excessive daytime sleepiness
  4. Both cancer treatments and cancer-related symptoms can contribute to insomnia (e.g. difficulty falling asleep, maintaining sleep, wakening too early or poor sleep quality, and impaired day-time functioning)
  5. Mood Disorders (e.g. depression & anxiety) 
  6. Existential spiritual distress or other psychiatric/ psychological disorders have a higher prevalence in the cancer palliative population
  7. Cognitive Impairment (e.g. delirium)
  8. Medications/toxins or medication withdrawal (e.g. diuretics, corticosteroids, stimulants, alcohol use)
  9. Generalized Insomnia
  10. Apnea

General Principles

  • Consider non-pharmacological management in all patients where sleep disturbance is having a significant impact on the patient’s quality of life or ability to function
  • Provide patients with the Sleep Problems Handout

Encourage the following behaviour

  • Promote good sleep hygiene 
    • Waking up at the same time every morning
      • Try not go to bed until feeling sleepy
      • Develop a relaxing bedtime ritual such reading something relaxing before going to bed
      • Try not to force sleep (e.g. If you go to bed and can't sleep, get up and do something relaxing and go back to bed when you feel sleepy)
      • Limit/avoid napping during the day
      • Limit/avoid caffeine and nicotine in the evening
      • Exercise early in the day and avoid exercising before bed as this can keep you up at night
      • Save your bedroom for sleep (and sex) only
      • Limit/avoid watching television or using mobile phones, tablets or computers in bed as these activate your brain
      • Try a warm bath a few hours before bed (this allows the body core to initially heat up and then gradually cool down in the hours prior to going to bed – mimicking what normally happens when we sleep)
      • Try a warm blanket from the dryer wrapped around the core when first going to bed (not a heating blanket as you want the blanket temperature to decrease over time)
      • Try some warm milk (this releases tryptophan which is a natural sleep aid)

Consider Environmental Factors

  • Keep bedroom dark and cool at night
  • Reduce ambient noise
  • The use of white noise machines

Complimentary Treatments

  • Cognitive and psychological therapies such as mindfulness: evidence supports 4-weeks of mindfulness and supportive group therapy to improve sleep quality and reduce depression scores
  • Bright-light therapy: to date there are inadequate disease specific studies, but this treatment is promising. Promote bright light exposure in the early hours of the morning and bright light avoidance, including light that comes from mobile phones, tablets or computers in the evening      

General Principles

The goal of therapy is to balance symptom control with careful protection of physical function and cognition. If non-pharmacological therapy alone fails, and sleep disturbance is having a severe impact on the patient’s quality of life and ability to function, a trial of pharmacological therapy can be considered.

  • Although there is limited evidence for pharmacological management of sleep disturbance small randomized controlled trials are available for the use of zolpidem and melatonin (note: cirrhosis)
  • Be cautious of using pharmacological interventions, as they increase risks of cognitive dysfunction and falls especially if daytime sleepiness is already present
  • Consider patient co-morbidities, concurrent medication interactions and side-effects, including over-the-counter and herbal remedies
  • Use sleep assessment tools to reassess the effectiveness of medications 2-4 weeks after prescription (see Helpful Links below)

Melatonin

  • 2-4 mg orally at night (least side effects)

Mirtazapine

  • 7.5 mg orally at night
  • Sedating at < 15 mg, i.e. no need to titrate up if ineffective at lower doses

Contraindicated in patients who are taking tramadol, antidepressants, or MAOIs

Treatment with mirtazapine can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted

Use with caution as may prolong QT interval along with other medications that may produce similar effects

Use with caution in moderate and severe hepatic impairment 
Risk of serotonin syndrome, QT prolongation and seizures 

  • May have added benefit of appetite stimulation and elevated mood

Trazodone

  • Usual recommended dose: 25-100mg PO 
  • Avoid abrupt discontinuation 

Avoid in people with dementia

Use in caution in Myocardial Infarction, also prolonged QT interval

Treatment with trazodone can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted

Risk of serotonin syndrome, QT prolongation and seizures as well as bleeding if combined with aspirin, NSAIDs, warfarin/antiplatelets

Doxepin

  • Starting dose 3 to 6 mg once daily within 30 minutes of bedtime 
  • Maximum dose: 6 mg/day

Contraindicated during acute recovery phase following myocardial infarction, acute congestive heart failure, and severe hepatic disease

  • Avoid abrupt discontinuation

Doxepin

Contraindicated in glaucoma. May prolong QT interval.

Contraindicated in patients with severe liver disease or heart failure. 

Zopiclone

  • 3.75 - 5 mg orally at bedtime for short term use (<2 weeks)

Contraindicated in patients with dementia and those who are taking tramadol, antidepressants, or MAOI

Contraindicated in severe hepatic insufficiency 
Contraindicated in severe impairment of respiratory function (e.g., significant sleep apnea syndrome) 
 

Use with caution in patients with depression or other mental health issues

  • Associated with clinical withdrawal reactions

Gabapentin

Off-label use for insomnia, generally in subtherapeutic doses or use when mechanism of action is desired e.g. insomnia associated with centralized pain syndromes (e.g., fibromyalgia, neuropathic pain, restless legs syndrome)

  • Starting dose 300 mg, orally at night. Titrate to tolerance and effect
  • Maximum dose: 1.2 g nightly

Use with caution in patients with Myasthenia gravis, kidney disease, heart failure, seizure disorder, and with history of substance use. Monitor for the common adverse effects of dizziness, impaired coordination, sleepiness/somnolence, confusion and possibly peripheral edema

May be associated with increased risk of peripheral edema in patients with heart failure

Pregabalin

Off-label use for insomnia, generally in subtherapeutic doses or use when mechanism of action is desired e.g. insomnia associated with centralized pain syndromes (e.g., fibromyalgia, neuropathic pain, restless legs syndrome).

  • Starting dose 75 mg orally at night. Titrate to tolerance and effect every 1 week
  • Maximum dose: 600 mg nightly
  • Do not discontinue abruptly. When discontinued, doses should be tapered over 1-2 weeks

Lemborexant

  • Severe insomnia, sleep onset or sleep maintenance: Oral 5 mg once daily, as needed, at bedtime with at least 7 hours before planned time of awakening; may increase to 10 mg based on response and tolerability

  • Maximum dose: 10 mg/day

Contraindicated for anyone with moderate or severe liver failure. Also, in severe kidney failure, patients may have more CNS side-effects such as drowsiness

One:carepath Sleep Problems Patient Handout

One:carepath Pain Patient Handout

One:carepath Shortness of Breath Patient Handout

One:carepath Itchiness Patient Handout

One:carepath Restless Legs Patient Handout

ESAS-r-Renal

Sleep Timing and Sleep Quality Screening Questionnaire - https://cirrhosiscare.ca/tools-provider/calculators-hcp/#

Epworth Sleepiness Scale - https://cirrhosiscare.ca/tools-provider/calculators-hcp/#calculatorNo35

Hepatic Encephalopathy: http://cirrhosiscare.ca/treatment-provider/hepatic-encephalopathy-hcp/