Key messages

  • Sleeping problems are highly prevalent among people with advanced illness requiring palliative care
  • Clinical assessment should focus on modifiable factors which may contribute to sleeping problems and on prognosis to determine likely length of treatment
  • Sedative hypnotics, especially benzodiazepines, are frequently prescribed to palliative care patients. They are likely to be effective in the short term but there is limited evidence to support long term use or the choice of medication. [1]
  • Side effects of sedative hypnotics may include worsening cognition and daytime sleepiness. [2]
  • There is limited evidence to support non-pharmacological interventions in sleeping problems in palliative care. [3]

Evidence summary

Definition and prevalence

Sleeping problems (insomnia and poor quality sleep) are common in people requiring palliative care, and often have a significant impact on quality of life. [3-6] They are particularly common in patients with COPD, [4] patients with heart disease, [7] end-stage renal disease, [5] end-stage liver disease, [8] and cancers associated with the lung [9] and the central nervous system. [10] The problems may be a combination of difficulty going to sleep, fragmented sleep, or early morning waking. Patients may complain that their sleep is not refreshing and sleep disturbances can exacerbate other symptoms such as pain. [6]

Insomnia can also be a problem for the patient’s caregivers and contributes to the burden of caregiving. [11] The sleeping problems of caregivers may continue into bereavement – either as a transient part of normal grief and bereavement, or a significant problem if the bereavement is complex or associated with depression.

Many life-limiting conditions or the treatments associated with these conditions cause sleep problems. There are a number of potentially modifiable problems which may contribute to sleeplessness: [12]

  • Depression, anxiety
  • Pain
  • Delirium
  • Obstructive sleep apnoea, or other primary sleep disorder
  • Dyspnoea, cough, pleural effusion
  • Nausea, vomiting
  • Movement disorders eg, restless legs, akathisia
  • Night sweats
  • Pruritis (itch)
  • Environmental disruption, especially for in-patients
  • Changed activity patterns
  • Altered circadian rhythm
  • Reduced bed mobility, and physical problems that limit comfortable sleeping position
  • Medications eg, steroids
  • Incontinence or nocturia.

Assessment

There are a number of screening and assessment tools for sleep disturbances. One of the most common, validated tools used in the general population is the Pittsburgh Sleep Quality Index (PSQI). [13] The Edmonton Symptom Assessment System (ESAS) was recently studied for its suitability to screen for sleeping problems in patients with advanced cancer. [13] The authors found the ESAS was appropriate to use and recommended routine screening for patients in a palliative care setting.

Treatment

A number of systematic reviews have examined both pharmacological and non-pharmacological interventions for sleep disturbances. A meta-analysis [1] was unable to identify sufficient evidence to draw conclusions about the use of benzodiazepines in palliative care. Agents that were included in the meta-analysis were all benzodiazepines, as well as zolpidem, zopiclone and zalpelon. Midazolam is the most commonly used benzodiazepam in palliative care, although it is rarely used specifically for sleeping problems and there is no evidence to support its use for sleep. [14] Melatonin has been used in a number of populations to assist with sleep. [15,16] It has been studied in advanced cancer with limited efficacy. [15]

Non-pharmacological interventions, such as exercise, sleep hygiene, mind-body practices and changes to the environment have been examined for efficacy at improving sleep. [3,17,18] There is low quality evidence to support these interventions. A systematic review of complimentary therapies in palliative care found no supporting evidence for these interventions to manage sleeping problems. [19]


Practice implications

  • Based on the available evidence, it is suggested that the clinical assessment of insomnia should focus on:
    • reversible factors which may contribute to sleeping problems
    • prognosis, which determines the length of time for which night sedation is likely to be needed, in order to minimise the use of long-term (greater than 8 weeks) sedative hypnotics.
  • The Edmonton Symptom Assessment System (ESAS) can be recommended for use in palliative care. [13]
  • If the patient has a prognosis of several months, non-pharmacological options for treatment should also be considered. [1]
  • Non-pharmacological interventions have limited evidence in the palliative care population, but in primary insomnia it may be beneficial to review environmental issues and sleep hygiene (including avoidance of napping and sleeping in where possible), behaviour therapies, and relaxation techniques. [3]
  • Medications which have sedating properties may contribute to night sedation (eg, tricyclic or other sedating antidepressants, antihistamines, or antipsychotics) but should be carefully assessed with regard to their side effect profile, and are likely to be best used where there is a specific indication. [1]

Evidence gap

  • There is evidence that chronic use of sedative hypnotics in palliative care patients results in increased side effects without long term efficacy. [1,2] Patterns of benzodiazepine use in palliative care patients, their effectiveness, and their adverse effects are being studied in phase 4 clinical trials.
  • Melatonin has been identified as a medication with the potential to reduce sleep latency, and may be an avenue for future research. [15]
  • There are few validated instruments for assessing and researching sleep problems in palliative care.


  1. Kvale EA, Shuster JL. Sleep disturbance in supportive care of cancer: a review. J Palliat Med. 2006 Apr;9(2):437-50.
  2. Bruera E, Fainsinger RL, Schoeller t, Ripamonti C. Rapid discontinuation of hypnotics in terminal cancer patients: a prospective study. Ann Oncol. 1996 Oct;7(8):855-6.
  3. Capezuti E, Sagha Zadeh R, Woody N, Basara A, Krieger AC. An Integrative Review of Nonpharmacological Interventions to Improve Sleep among Adults with Advanced Serious Illness. J Palliat Med. 2018 May;21(5):700-717. doi: 10.1089/jpm.2017.0152. Epub 2018 Jan 16.
  4. Chen YW, Camp PG, Coxson HO, Road JD, Guenette JA, Hunt MA, et al. A Comparison of Pain, Fatigue, Dyspnea and their Impact on Quality of Life in Pulmonary Rehabilitation Participants with Chronic Obstructive Pulmonary Disease. COPD. 2018 Feb;15(1):65-72. doi: 10.1080/15412555.2017.1401990. Epub 2017 Dec 11.
  5. Kennedy C, Ryan SA, Kane T, Costello RW, Conlon PJ. The impact of change of renal replacement therapy modality on sleep quality in patients with end-stage renal disease: a systematic review and meta-analysis. J Nephrol. 2018 Feb;31(1):61-70. doi: 10.1007/s40620-017-0409-7. Epub 2017 Jun 1.
  6. Dreier LA, Wager J, Blankenburg M, Zernikow B. The Unfavorable Alliance of Pain and Poor Sleep in Children with Life-Limiting Conditions and Severe Psychomotor Impairment. Children (Basel). 2018 Jun 21;5(7). pii: E82. doi: 10.3390/children5070082.
  7. Siouta N, van Beek K, Preston N, Hasselaar J, Hughes S, Payne S, et al. Towards integration of palliative care in patients with chronic heart failure and chronic obstructive pulmonary disease: a systematic literature review of European guidelines and pathways. BMC Palliat Care. 2016 Feb 13;15:18.
  8. Peng JK, Hepgul N, Higginson IJ, Gao W. Symptom prevalence and quality of life of patients with end-stage liver disease: A systematic review and meta-analysis. Palliat Med. 2019 Jan;33(1):24-36. doi: 10.1177/0269216318807051. Epub 2018 Oct 22.
  9. Papadopoulos D, Papadoudis A, Kiagia M, Syrigos K. Nonpharmacologic Interventions for Improving Sleep Disturbances in Patients With Lung Cancer: A Systematic Review and Meta-analysis. J Pain Symptom Manage. 2018 May;55(5):1364-1381.e5. doi: 10.1016/j.jpainsymman.2017.12.491. Epub 2018 Jan 6.
  10. Jeon MS, Dhillon HM, Descallar J, Lam L, Allingham S, Koh E-S, et al. Prevalence and severity of sleep difficulty in patients with a CNS cancer receiving palliative care in Australia. Neurooncol Pract. Online First 2019 Feb 19.
  11. Maltby KF, Sanderson CR, Lobb EA, Phillips JL. Sleep disturbances in caregivers of patients with advanced cancer: A systematic review. Palliat Support Care. 2017 Feb;15(1):125-140.Epub 2017 Jan 18.
  12. Phillips KM, Jim HS, Donovan KA, Pinder-Schenck MC, Jacobsen PB. Characteristics and correlates of sleep disturbances in cancer patients. Support Care Cancer. 2012 Feb;20(2):357-65. doi: 10.1007/s00520-011-1106-z. Epub 2011 Feb 11.
  13. Yennurajalingam S, Balachandran D, Pedraza Cardozo SL, Berg EA, Chisholm GB, Reddy A, et al. Patient-reported sleep disturbance in advanced cancer: frequency, predictors and screening performance of the Edmonton Symptom Assessment System sleep item. BMJ Support Palliat Care. 2017 Sep;7(3):274-280. doi: 10.1136/bmjspcare-2015-000847. Epub 2015 Oct 16.
  14. Zaporowska-Stachowiak I, Szymański K, Oduah MT, Stachowiak-Szymczak K, Łuczak J, Sopata M. Midazolam: Safety of use in palliative care: A systematic critical review. Biomed Pharmacother. 2019 Jun;114:108838. doi: 10.1016/j.biopha.2019.108838. Epub 2019 Apr 10.
  15. Lund Rasmussen C, Klee Olsen M, Thit Johnsen A, Petersen MA, Lindholm H, Andersen L, et al. Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: A double-blind placebo-controlled crossover trial. Cancer. 2015 Oct 15;121(20):3727-36. doi: 10.1002/cncr.29563. Epub 2015 Jul 15.
  16. Foster J, Burry LD, Thabane L, Choong K, Menon K, Duffett M, et al. Melatonin and melatonin agonists to prevent and treat delirium in critical illness: a systematic review protocol. Syst Rev. 2016 Nov 24;5(1):199.
  17. Heywood R, McCarthy AL, Skinner TL. Efficacy of Exercise Interventions in Patients With Advanced Cancer: A Systematic Review. Arch Phys Med Rehabil. 2018 Dec;99(12):2595-2620. doi: 10.1016/j.apmr.2018.04.008. Epub 2018 May 5.
  18. Lee J, Kim Y, Kim Y. Non-Pharmacological Therapies for Sleep Disturbances in People with Parkinson's Disease: A Systematic Review. J Adv Nurs. 2018 Apr 27. doi: 10.1111/jan.13694. [Epub ahead of print]
  19. Zeng YS, Wang C, Ward KE, Hume AL. Complementary and Alternative Medicine in Hospice and Palliative Care: A Systematic Review. J Pain Symptom Manage. 2018 Nov;56(5):781-794.e4. doi: 10.1016/j.jpainsymman.2018.07.016. Epub 2018 Aug 2.

Last updated 27 August 2021