Sleep problems in advanced disease 

Key points

• Sleep problems are common in patients with advanced disease.

• Sleep problems are associated with significant morbidity in patients with advanced diseases.

• Insomnia is often secondary to related physical symptoms (and psychological problems).

• Management of insomnia primarily involves treatment of perpetuating factors, sleep hygiene measures, and non-pharmacological interventions (cognitive behavioural therapy).

Insomnia

Insomnia has been defined as ‘a persistent difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, and results in some form of daytime impairment’.³ Patients with advanced cancer often report ‘insomnia’, and many meet the diagnostic criteria for short-term insomnia disorder (Box 1), or even chronic insomnia disorder (ie the sleep disturbance and associated daytime symptoms have been present for at least 3 months, and the sleep disturbance and associated daytime symptoms occur at least three times per week).³ However, the prevalence of these sleep disorders is unknown in this group of patients. Nevertheless, researchers have reported that 62–70% patients with advanced cancer had poor sleep quality as assessed by the Pittsburgh Sleep Quality Index.^5,6

Davies et al reported that in their study of 174 patients with advanced cancer, 30% patients had trouble sleeping because they couldn't get to sleep within 30 minutes three or more times a week during the previous month, and that 60% patients had trouble sleeping because they woke in the middle of the night or early morning three or more times a week in the previous month.⁵ It should be noted that the quality of sleep is not always related to the duration of sleep,⁷ and that it is often worse among inpatients (as compared to outpatients),^5,8 and often poor among carers (cf general population).^7,9 Indeed, the prevalence of insomnia in carers is not dissimilar to that in patients with advanced cancer.⁹

In most cases, the insomnia develops following the diagnosis,^10,11 and it may be precipitated by the cancer per se, the cancer treatment and/or concomitant physical symptoms and psychological problems.¹¹ Furthermore, it may be perpetuated by similar factors, as well as by environmental factors, maladaptive thinking (relating to sleep) and maladaptive behaviours (relating to ‘sleep hygiene’).¹¹ Hugel et al reported that in their study of 73 patients with advanced cancer, 60% patients related their insomnia to uncontrolled physical symptoms (predominantly pain and urinary frequency).¹⁰

Insomnia may be associated with daytime sleepiness, cognitive impairment, accidents/injuries, anxiety,¹² depression,¹² delirium,¹³ fatigue and, unsurprisingly, impaired quality of life.¹⁴ Insomnia is associated with suppression of the immune system, which may have implications in terms of development of infections, and also progression of cancers. Indeed, insomnia has been shown to be associated with a decreased response to chemotherapy, and with a decreased (overall) survival, in an observational study of 361 patients with metastatic colorectal cancer.¹⁵

The management of insomnia includes treatment of perpetuating factors (eg physical symptoms, psychological problems), sleep hygiene measures (Box 2), non-pharmacological interventions (eg cognitive behavioural therapy, exercise), pharmacological interventions and combination of modalities.¹⁶ Pharmacological interventions should be used with care, restricted to patients with related distress and prescribed for only short periods (and intermittently rather than continuously; Box 3).¹⁷ The choice of hypnotic depends on a variety of factors, including the clinical features of the insomnia.¹⁷

Vivid dreams

Vivid dreams (defined as ‘unusually clear, long dreams with elaborate scenarios and possibly strong emotions, that occurred only when sleeping and were acutely remembered’) appear to be common in patients with advanced cancer (34.5% in the previous month).⁵ Other investigators have reported an even higher prevalence in this population.⁷ Vivid dreams are associated with sleep disturbance,⁵ which increases the risk of waking up during REM sleep (which is the sleep stage primarily associated with dreaming). Vivid dreams are also associated with a higher psychological symptom burden,⁵ which itself is associated with sleep disturbance.¹¹ However, vivid dreams do not appear to be more common with worse performance status (a surrogate for worse prognosis), and were not associated with the use of opioid analgesics in an observational study of 174 patients with advanced cancer.⁵

Patients reporting vivid dreams should be assessed for underlying sleep disturbance and/or psychological problems, and these should be appropriately managed (the management of sleep disturbance is discussed in the previous section). Specific treatment is invariably not required, although patients may require reassurance about the significance of the vivid dreams.

Nightmares

Nightmares appear to be common in patients with advanced cancer (18% in the previous month),⁵ although not necessarily more common than in the general population.¹⁸ Nightmares are associated with sleep disturbance in the general population,¹⁹ and in patients with advanced cancer,⁵ and it has been suggested that the sleep disturbance precipitates (recall of) the nightmares, rather than the nightmares precipitating the sleep disturbance.²⁰ Nightmares are associated higher physical and psychological burden,⁵ which themselves are associated with sleep disturbance.¹¹ However, nightmares do not appear to be associated with the use of opioid analgesics in two observational studies of 297 patients with advanced cancer (or a review of opioid adverse effects),^5,21,22 although there are a number of other drugs that can precipitate nightmares (eg sedatives/hypnotics, beta blockers, amphetamines, dopamine agonists).

Patients reporting nightmares should be assessed for underlying sleep disturbance and/or physical and psychological problems, and these should be appropriately managed. Specific treatment is generally not required, but in those cases that meet the diagnostic criteria for ‘nightmare disorder’ (ie related/specific sleep disorder), recommended treatments include specific behavioural and psychological interventions (eg image rehearsal therapy, cognitive behavioural therapy), and specific pharmacological interventions (eg nitrazepam, prazosin).²³