Sleep disturbances in cancer

A cancer diagnosis alone may cause patients to have difficulty sleeping.

When even the knowledge of a cancer diagnosis can disrupt sleep, it is no wonder that patients receiving treatment for cancer have a higher incidence of sleep disturbances, from 19% to 63% as compared with the general population of 15% to 20%.

Sleep complaints reported commonly by patients with cancer include insomnia, restless limbs and daytime sleepiness; for patients with head and neck cancer, breathing disturbances such as obstructive sleep apnea can also occur. Sleep disturbances, much like fatigue, are under-reported by patients and presumed to be expected and normal. Much of the literature in patients with cancer has focused on symptoms of insomnia, defined broadly as the difficulty with onset or maintenance of sleep associated with daytime dysfunction (fatigue, sleepiness, attention deficits, etc), in which the difficulty occurs even with adequate opportunity for sleep.

Contributing factors

Why do patients with cancer so frequently report sleep disturbances? First, receiving the diagnosis of cancer itself has been noted as a precipitating factor to sleep problems. Studies have also shown that patients with poorly controlled physical symptoms have a higher risk for sleep disturbance. Sleep disturbances can worsen pain, and vice versa. As one might imagine, cancer-related fatigue and sleep have a close relationship, as changes in daytime sleeping patterns (ie, addition of naps) due to fatigue can cause difficulty in sleep onset or sleep maintenance at night.

Stephanie Harman

Cancer treatments have also been shown to disrupt normal sleep. In multiple studies, patients receiving chemotherapy have reported sleep disturbances at higher rates, likely due to treatment side effects such as nausea and peripheral neuropathy. Patients with breast cancer report frequent sleep disturbance due to hot flashes as a side effect of hormonal deficiencies. Other commonly used medications in cancer therapy, such as steroids and certain antiemetics, can lead to insomnia. Comorbid conditions can put patients with cancer at higher risk for sleep disturbances. Both depression and anxiety cause disruptions in sleep patterns; these diagnoses, if pre-existing, can be exacerbated in the setting of cancer or may develop concomitantly.

Evaluation

Initial evaluation for sleep disturbances includes a sleep history exploring the patient’s specific complaints, sleep-wake patterns and daytime consequences. A thorough review of other symptoms is warranted to determine the existence of comorbid conditions, as well as a physical exam and a mental status exam. Sleep disturbance surveys, such as the Epworth Sleepiness Scale or the Pittsburgh Sleep Quality Index, can help measure the severity of symptoms. Polysomnography is recommended for patients in whom sleep apnea or movement disorders are suspected, but not necessarily for patients with insomnia.

Treatment approaches

For the initial approach to complaints of sleep disturbances, establishing good sleep hygiene can be an effective place to start. This includes establishing a regular sleep schedule, having a quiet sleep environment, avoiding daytime napping, if possible, and avoiding stimulants such as caffeine and nicotine. The treatment of comorbid symptoms, particularly pain and depression, has a significant role in treating sleep disturbances of cancer patients, as comorbid symptoms are very common.

In restless leg syndrome, nonpharmacologic therapy includes eliminating exacerbating medications and the treatment of iron deficiency. Primary pharmacologic agents used are non-ergot dopamine agonists, such as pramipexole or ropinirole, or levodopa/carbidopa.

In patients with sleep apnea related to head and neck cancer, often the typical treatment strategies of behavior modification and weight loss are not effective. Behavior modification does not address the underlying pathology; primarily, anatomic changes related to the cancer itself or treatment. Besides noninvasive positive pressure ventilation, other interventional/surgical techniques may be required that are specific to the patient’s anatomy.

For insomnia specifically, both nonpharmacologic and pharmacologic treatments have demonstrated improvement in sleep, with a combination of these therapies being most successful. Nonpharmacologic treatments include:

• Stimulus control therapy, in which patients do not remain in bed if they cannot fall asleep after a set period of time.
• Relaxation training, such as guided imagery.
• Cognitive behavioral therapy, which combines behavioral therapies with cognitive therapy.

Pharmacologic therapy of insomnia has not been well studied in patients with cancer, but practice parameters for insomnia from the American Academy of Sleep Medicine indicate the use of short- or intermediate-acting benzodiazepine receptor agonists as initial therapy. This class includes medications such as zolpidem, temazepam and eszopiclone. If the first agent does not work, it is reasonable to try an alternative from this same class. Ramelteon (Rozerem, Takeda), a melatonin agonist, can also be used as an initial agent. If the patient has comorbid depression or anxiety, the sedating antidepressants can be used, including trazodone or mirtazapine. Combination therapy of a benzodiazepine receptor agonist plus a sedating antidepressant should be reserved only for when a single agent fails.

Current research in sleep disturbance has been examining the link between circadian rhythm disturbances and cancer, both from the standpoint of cancer-related alterations, as well as an increased risk of cancer seen in nightshift workers. As there have been no trials of pharmacologic sleep agents in cancer patients, more research is needed on this common and distressing symptom.

Stephanie Harman, MD, is a Palliative Care Physician at Stanford University Medical Center and Director of its Inpatient Palliative Care service.

For more information:

• Davidson JR. Soc Sci Med. 2002; 54:1309-1321.
• Kvale EA. J Pall Med. 2006; 9:437-450.
• Schutte-Rodin S. J Clin Sleep Med. 2008;4:487-504.