Sleep disturbances in cancer patients: Underrecognized and undertreated
ABSTRACTSleep-related complaints are extremely common in patients with cancer but often are not recognized, and even if they are, they are seldom treated. Recognizing insomnia in cancer patients is imperative, as appropriate treatment can improve quality of life.
KEY POINTS
- Sleep disturbances, primarily insomnia, profoundly affect all aspects of quality of life.
- Insomnia can be caused or worsened by a number of other conditions, such as pain, fatigue, depression, and anxiety, and these in turn can be worsened by insomnia.
- Cognitive-behavioral therapy is the treatment of choice for chronic insomnia. Underlying problems should be addressed.
- Drugs are often prescribed to help cancer patients sleep but should be used with caution, as there is limited information from clinical trials in this population.
POOR SLEEP AND CANCER RISK AND OUTCOMES
Sleep disturbances have negative health consequences in cancer. Their impact ranges from plausible carcinogenesis to affecting the course of the disease and cancer survival.
Poor sleep and risk of cancer
Epidemiologic studies have examined a possible link between circadian rhythm disruption and breast cancer risk, using both direct measures such as melatonin levels and indirect measures such as sleep duration and shift work. (Melatonin production is related to sleep duration, and night-shift work leads to disruption of sleep pattern and quality of sleep, thus lowering melatonin levels.59)
The findings were mixed. Breast cancer risk was significantly and inversely associated with urinary melatonin levels (6-sulfatoxymelatonin) in the Nurses’ Health Study II,60 but not in the Guernsey III study in the United Kingdom.61 Breast cancer risk was significantly lower with longer sleep duration in Finnish women62 and in Chinese women in Singapore,63 but not in American women.64,65 Results of three cohort studies66–68 and two case-control studies69,70 suggested a higher breast cancer risk in women who work evening or overnight shifts. Shorter sleep duration was associated with a higher risk of colorectal adenomas.71
These studies make a strong case for an association of cancer with circadian rhythm disruption and shorter sleep duration, possibly from an effect on melatonin levels. However, one should be cautious in interpreting epidemiologic studies: although they show sleep disturbances to be associated with cancer risk, they do not establish causality.
Insomnia and cancer outcomes
Evidence is growing that sleep disturbances may affect compliance with treatment, immune function, and outcomes—including survival—in cancer patients.23,24
In patients newly diagnosed with various types of cancer, Degner and Sloan72 showed that those who suffered from insomnia, nausea, poor appetite, and pain had a lower survival rate at 5 years, independent of the cancer stage. However, no separate analyses were performed to examine the specific influence of insomnia on cancer survival.
Thompson and Li73 analyzed data from 101 breast cancer patients with available Oncotype DX recurrence scores (a proprietary genetic test performed on tumor tissue that predicts the likelihood of recurrence). The scores were strongly correlated with average hours of sleep per night before breast cancer diagnosis, with fewer hours of sleep associated with a higher (worse) score.
Since these studies were retrospective and merely suggest associations, prospective studies, using more standardized questionnaires and objective measures, are needed to establish causality and to further our understanding of the mechanisms involved.
HELPING CANCER PATIENTS SLEEP BETTER
Insomnia is generally diagnosed with a thorough history that includes sleep, medical issues, substance use, and psychiatric issues. The sleep history should include specific insomniarelated complaints, presleep conditions and habits, sleep-wake habits, other sleep-related symptoms, and daytime consequences. To obtain the information, one can use questionnaires, sleep logs, psychological screening tests, and bed-partner interviews.74
Managing insomnia involves both pharmacologic and nonpharmacologic treatment. It is also important to treat the associated disorders such as depression and anxiety disorders that often accompany insomnia. Long-term management of cancer patients should not be limited to surveillance of cancer but should also involve aggressive treatment of clusters of symptoms such as insomnia, cancer-related fatigue, and pain to yield better long-term quality of life.75–77
Nonpharmacologic treatment: Cognitive-behavioral therapy
Nonpharmacologic interventions use psychological and behavioral therapies. The American Academy of Sleep Medicine guidelines recommend cognitive behavioral therapy for all patients with insomnia, either alone or in combination with hypnotic medications.
Cognitive-behavioral therapy for insomnia includes various components that help the patient learn coping skills and ways to prevent or mitigate the severity of future episodes (Table 3). Various randomized controlled trials found it to be effective for treating insomnia in the general population.77–79
Several studies found that cognitive-behavioral therapy for insomnia was effective in cancer patients, not only improving sleep quality but also decreasing psychological distress, resulting in better overall quality of life.80,81
Savard et al81 conducted a randomized controlled trial of cognitive-behavioral therapy for insomnia in 57 patients with breast cancer, examining subjective and objective sleep measures, psychological functioning, quality of life, and immunologic responses. They found significant improvements in sleep efficiency, mood, quality of life, depression, anxiety, and need for sleep medications. Improvements in subjective sleep measures persisted on 12-month follow-up.
Berger et al,82 in another randomized controlled trial, assessed behavioral therapy using stimulus control, modified sleep restriction, relaxation therapy, and sleep hygiene in breast cancer patients receiving adjuvant chemotherapy. Behavioral therapy improved sleep quality over time, as measured by the Pittsburgh Sleep Quality Index.
Espie et al83 evaluated the effect of cognitive-behavioral therapy on prostate, colorectal, gynecologic, and breast cancer patients, with similar results.83
Cognitive-behavioral therapy is at least as effective as drug therapy for insomnia in the general population. In the limited studies done in cancer patients, it has been shown to be effective irrespective of the type of cancer and is associated with better long-term outcomes. It diminishes the distress associated with early insomnia, can reduce anxiety, and can promote sleep.
A National Institutes of Health conference on insomnia concluded that cognitivebehavioral therapy is at least as effective as medications for brief treatment of chronic insomnia and that its beneficial effects, in contrast to those produced by medications, may last beyond the termination of treatment.84
It is important to think about numerous factors when considering options such as cognitive-behavioral therapy, as patients with cancer have different complications that may affect sleep quality, such as cancer-related fatigue, cancer-related depression, psychological reactions to the disease, side effects of treatment, and cancer-related pain. These need to be addressed as well.
If cognitive-behavioral therapy is not available, self-help interventions (eg, written material, videos, television and Internet resources) can be used. These have several advantages over professionally administered interventions, including greater accessibility, less burden for the patient, and lower cost. Research is under way evaluating this approach in cancer patients.85
