REVIEW ARTICLE
Nonpharmacologic Approach to Sleep Disorders J. Keith Mansel, MD and Elise C. Carey, MD Abstract: Sleep disturbances are common in patients with cancer, occurring throughout the disease trajectory and sometimes well after treatment has concluded. Insomnia often does not occur in isolation; it may be associated with pain, fatigue, depression, and medication usage. Screening for sleep disturbances is an essential part of caring for oncologic patients. The criterion standard for nonpharmacologic treatment of insomnia in these patients is cognitive-behavioral therapy, a multimodal approach using sleep hygiene and education, stimulus control, sleep restriction, and relaxation. Exercise and complementary and integrative medicine have been studied with varying results, and no firm recommendation can be made about their efficacy. Key Words: Cancer patients, sleep disorders, nonpharmacologic approaches, screening
other sleep-related disorders such as sleep-disordered breathing and periodic limb movements of sleep may occur.23 In this article, we provide a practical framework for evaluating and caring for cancer patients with sleep disruption and insomnia syndrome. (See also schematic in Fig. 1.) We examine the etiology of sleep disorders, including concomitant symptoms and other precipitating factors that, when treated, may improve sleep. We delineate strategies for screening patients for sleep disturbances, and we review the evidence for nonpharmacologic interventions used to treat insomnia, including sleep hygiene education, behavioral techniques, cognitive-behavioral therapy (CBT), exercise, and complementary therapies. Finally, we briefly discuss combination therapy and how sleep disturbances impact caregivers.
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leep disturbances are common among oncology patients, throughout the course of the disease and even extending into the survivor phase. Studies reveal that from 25 to 59% of oncology patients have some type of sleep disruption, which is nearly double the prevalence of the general population.1–4 Impaired sleep in patients with cancer results in worse patient-reported outcomes, including diminished quality of life, difficulty performing activities of daily living, and coping ineffectively with sleep disturbance.6,7 Higher levels of sleep disruption are often associated with other distressing symptoms in cancer patients, including fatigue, depression, and pain.8–10 Moreover, epidemiologic studies suggest that sleep disturbances are associated with an increase in cancer risk, disease progression, and poorer prognosis.12–17 Although the exact relationship is unknown, a growing body of evidence suggests that disturbed sleep may influence immune function18 and dysregulation of the circadian rhythm,19–21 which may further mediate dysregulation of the neuroendocrine system. Despite its clear impact on patient-reported quality-of-life measures and potential association with worse patient outcomes, sleep-related complaints are underreported, underrecognized, and undertreated.22 What, then, counts as sleep disturbance, and when does it require intervention? Sleep disturbance or insomnia symptoms manifest as the transient inability to either initiate or maintain sleep for a period of greater than 2 weeks, often occurring in the setting of an acute stressor. Acute insomnia can last up to 1 month and is characterized by poor quality, nonrefreshing sleep that results in poor daytime functioning. Insomnia syndrome, in contrast, is characterized as insomnia occurring more than 3 nights per week; difficulty falling asleep or nighttime awakenings (>30 minutes); poor sleep efficiency, defined as the ratio of sleep time to time spent in bed of less than 85%; and patient sense of distress and impaired daytime functioning.4 Insomnia is the most widely described sleep disturbance in cancer patients, although From the College of Medicine, Mayo Clinic, Rochester, MN. The authors have disclosed that he/she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Reprints: J. Keith Mansel, MD, Mayo Clinic, 200 First St SW, Rochester, MN. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 1528-9117
The Etiology of Insomnia: Predisposing, Precipitating, and Perpetuating Factors Spielman and Glovinsky24 have described the etiologic factors of insomnia as (1) predisposing factors, or enduring traits that increase the person’s general vulnerability to develop insomnia, (2) precipitating factors that trigger the onset of insomnia; and (3) perpetuating factors that contribute to the maintenance of insomnia over time. Factors that predispose cancer patients to insomnia include being female or having an inherent hyperarousability trait, a personal or family history of insomnia, or an anxiety or mood disorder.1,3,25–27 Interestingly, although older age predisposes to insomnia in the general population, there is some evidence that insomnia is more prevalent in younger individuals with cancer.1,25 This could be linked to high levels of psychological distress in younger patients with cancer, as well as the increased propensity for many younger women to experience menopause transition during cancer treatments.28 There are myriad factors that can precipitate sleep disturbances, including a stressful work environment, divorce, and death of a family member.29 Medical conditions and illnesses such as cancer can also precipitate insomnia, as can uncontrolled symptoms, such as pain, dyspnea, fatigue, and depression.29 Several transition points in the trajectory of illness for cancer patients may predispose for insomnia. These include the time of initial diagnosis, recurrence or progression of disease, hospitalization, and surgery.23 Inflammatory cytokines such as interleukins 1 and 6, as well as tumor necrosis factor α, may be produced by cancer cells and have some effect on the sleep-wake cycle.18 Insomnia may also be associated with chemotherapy leading to treatment associated fatigue, mood disorders, daytime napping, and alteration of circadian rhythm.4,6 In addition, medications used commonly in cancer patients such as antiemetics, steroids, and opioids can all play a role in altered sleep-wake cycles.30,31 Hormonal therapy such as antiandrogens and antiestrogens can lead to insomnia via hot flashes and night sweats.28 Perpetuating factors of insomnia in patients with cancer include maladaptive behaviors, such as spending an excessive amount of time in bed and daytime napping, and altered cognition, in which patients have unrealistic expectations of sleep and faulty perceptions of the consequences of insomnia.29 Both of these maladaptive factors may lead to heightened arousal and performance anxiety, thus worsening sleep disruption. Finally,
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FIGURE 1. Suggested screening and treatment schematic for sleep disorders.
inappropriate use of sleep aids as well as other heretofore mentioned medications can perpetuate insomnia in cancer patients.32
Screening and Assessment Given the prevalence of insomnia and sleep disturbance among cancer patients, we recommend that all cancer patients be screened for insomnia at the time of their initial visit and intermittently throughout the course of their illness (Fig. 1). Symptom clusters such as pain, fatigue, and depression, as well as the use of medications that may affect sleep, should be clues to the clinician to ask about sleep disturbances. Of note, many commonly used screening tools, including the Edmonton Symptom Assessment Score commonly used by oncologists and palliative care physicians, do not include any screening for insomnia.33 Fortunately, initial screening for insomnia need not be burdensome. Buysse et al34 recommend a 2-step process for screening and assessment of sleep disturbances, including the questions: (1) do you have problems with your sleep or sleep disturbance on average for 3 or 4 nights a week? If yes, then (2) does the problem with
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your sleep negatively impact your daytime functioning? If the answer to both questions is yes, then a more detailed assessment is warranted. Some available assessment tools include the Epworth Sleepiness Scale,5 the Insomnia Severity Index,35 and the Pittsburgh Sleep Quality Index.36
Treatment Multiple factors contribute to insomnia for any given patient, and, as such, management requires a multifaceted approach. We will be focusing on nonpharmacologic interventions for improving sleep, including the use of sleep hygiene and behavioral therapies, CBT, exercise, and complementary and integrative medicine (CIM) strategies. Because sleep disruption often does not occur in isolation in cancer patients, treatment of other symptoms such as pain and depression is paramount. Although the scope of this article is limited to nonpharmacologic treatment, medications are sometimes used on a temporary basis as a stop-gap measure, while more enduring nonpharmacologic interventions and coping strategies are put in place. © 2014 Lippincott Williams & Wilkins
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Treatment of Sleep Disorders
TABLE 1. Overview of Nonpharmacologic Treatment of Insomnia in Patients With Cancer Intervention
Objective
Sleep hygiene and behavioral interventions Education Improve factors that enhance sleep and discourage behaviors that interfere with sleep
Stimulus control
Associate the bed/bedroom with sleep
Maintain a consistent sleep-wake cycle
Sleep restriction therapy
Specifics Education about • Normal sleep • Circadian rhythm • Environmental factors affecting sleep • Go to bed only when sleep • Use the bed for sleeping only (no TV, video games, reading in bed) • Leave the bed if unable to sleep • Go to bed at the same time every night • Wake up at the same time every morning • Avoid daytime naps
Improve sleep efficiency by limiting the time in bed to the actual time spent asleep
• This is based on the theory that sleep is regulated by homeostatic and circadian mechanisms • If one is spending 9 h in bed but sleeping only 6 h, then the time in bed should be restricted to 6 h, with periodic adjustments
Reduce somatic tension and thoughts that inhibit sleep
Relaxation exercises can reduce muscle tension and redirect intrusive thoughts. Examples include the following: • Progressive muscle relaxation • Guided imagery • Meditation
Identify and change misguided and mistaken beliefs and attitudes about sleep and insomnia
• Uses psychological and cognitive methods to challenge fears • May include journaling and counseling
Relaxation training
Cognitive therapy
Cognitive-behavioral therapy Combined therapy using some or all of the above noted techniques
More than 50 studies have been performed evaluating nonpharmacologic therapy for insomnia in cancer patients, and the most elegant consist of CBT interventions.37–39 Most are not randomized controlled trials and are represented primarily by female patients, aged 51 to 55 years, and individuals with breast cancer.40 The most robust data exist for the use of sleep hygiene and CBT, and they represent the cornerstone of nonpharmacologic interventions for insomnia in patients with cancer.39 Whether the incidence and prevalence of insomnia are related to the type of cancer or the overall health status, disease, and symptom burden of the individuals has not been well elucidated in studies to date. The benefit of specifically targeting other cancer-related symptoms such as fatigue and depression remains elusive. In addition, most of the studies assessed patients months to years after the completion of therapy.40 It seems reasonable to assume that sleep disturbances may differ for patients undergoing active treatment, surgery, or radiation. The types of measures used to evaluate sleep disturbances in the available studies have proven to be highly inconsistent. Despite the number of studies of insomnia in oncologic patients, few have evaluated sleep as © 2014 Lippincott Williams & Wilkins
• Sleep hygiene education • Stimulus control • Sleep restriction • Relaxation training • Cognitive therapy
the sole primary outcome, and most do not discuss the clinical significance of the interventions studied.40 Below, we review the primary nonpharmacologic interventions recommended for sleep disruption and insomnia, including the evidence associated with each treatment. Our goal is to provide clinical guidance to clinicians caring for patients with sleep disruption. These interventions generally fall into 4 categories: (1) sleep hygiene and education including behavioral strategies, (2) CBT, (3) exercise, and (4) CIM (Table 1). There are distinct treatments within these categories, each with a varying level of evidence. Many of the interventions share commonalities, including providing education on sleep hygiene and relaxation and training patients in coping skills and cognitive reframing regarding their sleep disruption.
Sleep Hygiene and Behavioral Interventions Education about sleep hygiene, together with stimulus control, relaxation, and sleep restriction therapy, forms the basis of behavioral therapy.41 Key to treatment of sleep disturbances in patients with cancer, they have the benefit of being able to be performed in the provider’s office setting (Tables 1 and 2). www.journalppo.com
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TABLE 2. Office Tips for Helping Patients With Cancer Sleep Better Intervention
Specific Techniques
Take a sleep history
• Do you have trouble sleeping? • Does your sleep problem affect your daytime functioning? • How often do you have insomnia? • What time do you go to bed and arise, both weekdays and weekends? • What are your activities at bedtime? • What medications are you taking? • Do you use sleep aids? • Do you use stimulants such as caffeine or nicotine?
Screen for sleep disorders
• If trouble with sleep and daytime functioning, use an objective measure such as the Epworth Sleepiness Scale and a sleep diary • Screen for other sleep disorders such as obstructive sleep apnea and restless legs syndrome
Evaluate comorbid conditions and medications
• In patients with cancer • Review medications that can affect sleep such as opioids
Sleep hygiene and behavior therapy
• Maintain a consistent sleep schedule by arising and going to bed at the same time every day • Sleep as long as necessary to feel refreshed upon awakening • Do not watch TV, play video games, or worry in bed • Avoid forcing sleep • Avoid alcohol and nicotine in the evening • Limit caffeine intake to the morning • Regular exercise improves sleep quality, but avoid within several hours of bedtime • Any daytime naps should be brief and should not occur late in the day • Go to bed only when sleepy If unable to fall asleep within 20 min, leave the bedroom and return when sleepy
Some components of sleep hygiene include maintaining a consistent sleep schedule by arising and going to bed on a regular schedule, sleeping as long as necessary to feel refreshed upon awakening, avoiding stimuli near bedtime such as television, and relaxing before bedtime. Other helpful techniques include not forcing sleep, avoiding alcohol and nicotine in the evening, and limiting caffeine intake to the morning. Regular exercise, but not within several hours of bedtime, can improve sleep quality. If daytime naps are utilized, they should be brief and should not occur late in the day.32 The American Academy of Sleep Medicine recommends sleep hygiene education as an integral part of any therapy for insomnia, although there are insufficient data to suggest using this technique as standalone therapy.42 Stimulus control therapy is related to an individual’s association of the bedroom with sleep disturbance and fear of insomnia.32 This can lead to a vicious cycle, so that the longer one stays in bed, the greater the association comes. Techniques that have been proven to be useful are going to bed only when sleepy, confining the use of the bed primarily for sleeping (not watching television or checking e-mail) and, if unable to sleep within 20 minutes, getting out of bed and undertaking a relaxing pursuit such as reading.32 Activities that promote relaxation include auditory and visual biofeedback, guided imagery, progressive muscle relaxation using one muscle group at a time, and abdominal breathing to redirect thoughts to a neutral mental stance. 43 The final component of behavioral therapy for insomnia involves sleep restriction. Because some patients tend to sleep late to make up for their inability to sleep, their circadian rhythm is altered, making the initiation of sleep the following night ever the more difficult. Sleep restriction therapy aims to decrease the time spent in bed to the actual time spent in bed, often through
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the use of sleep diaries.32 For instance, if one is spending 9 hours in bed but the diary indicates the time spent asleep is 6 hours, then the time from going to bed until arising should be restricted to 6 hours. Adjustments to this can be made over time depending on the degree of sleep efficiency.
Cognitive-Behavioral Therapy Cognitive-behavioral therapy is the most well-studied nonpharmacologic intervention for insomnia in cancer patients32,44,45 and the only type of intervention noted “likely to be effective” TABLE 3. Cognitive Reframing Tips for Helping People Cope With Misconceptions About Sleep Negative thoughts (1) If I don’t sleep tonight, I will never get a restful night’s sleep. (2) If I don’t get a good night’s sleep tonight, I won’t be able to function at work tomorrow. (3) I must keep looking at the clock if I am not sleeping. (4) I can’t help that I am a worry wart. Positive thoughts (1) Tonight is just 1 night of poor sleep. (2) An occasional night of bad sleep does not mean I can’t function well the next day. (3) Looking at the clock only leads to anxiety and does not help me sleep. (4) Worrying does nothing to help me sleep. I can worry and deal with issues in the morning.
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based on the Oncology Nursing Society “Putting Evidence Into Practice” classification document.46 Cognitive-behavioral therapy is a multimodal intervention, bringing together the aforementioned sleep hygiene and behavioral techniques with cognitive therapy (Table 1). The cognitive portion of CBT involves redirecting negative or irrational thoughts about sleep. Thoughts, perceptions, and beliefs can affect physical and emotional reactions to particular situations such as the inability to initiate or maintain sleep. Negative self-talk can lead to a vicious cycle of distress and irrational thoughts regarding sleep disturbances. Cognitive therapy seeks to educate patients about positive coping skills to allay negative thinking and rumination. Table 3 lists some ways to deal with illogical beliefs, fears, and thoughts about sleep.47 More than a dozen studies have been performed evaluating CBT in insomnia in cancer patients.38–40 Most of these studies have been performed since 2000 and reveal evidence of improved sleep quality and less psychological distress. Savard et al48 studied 57 patients with breast cancer using a randomized controlled trial of CBT. They discerned improvements in sleep, depression, quality of life, anxiety, and the use of sleep aids. Importantly, these changes continued at 12-month follow-up. Espie et al49 and Berger et al50 have also performed randomized controlled trial of CBT in oncologic patients and have likewise demonstrated benefits in sleep quality and efficiency. Cognitive-behavioral therapy can be conducted in groups or individually and usually consists of several sessions. Whether 1 particular component (sleep hygiene, cognitive reframing, or behavioral interventions) is more effective than others is unknown.51 Most CBT interventions that have been studied use a standardized program, although some efforts at tailored therapies have been cited.52–55 Cognitive-behavioral therapy–trained professionals are not readily available in some areas, and an increasing number of Internet-based CBT programs are available, although more data about their efficacy are needed.56 An Individualized Sleep Promotion Plan, an adaptation of CBT for cancer-related insomnia, has recently been touted as helpful, although further work is needed.52,57 A stepped-care approach has been suggested utilizing a self-administered or Internet program initially, followed by referral to a CBT-trained professional if the original intervention proves not to be effective.58
(MBSR),9,65–69 yoga, 70massage,71,72 healing touch,73 spirituality,74 and expressive writing.75 Most of these therapies focus on negative thought patterns and redirecting irrational emotions. Studies have often been small, revealed mixed results, and did not use sleep disturbance as the primary outcome. Four clinical trials studying the benefit of acupuncture on sleep disturbance in cancer patients were recently reviewed, and some small improvements were noted.64 Garland et al65 recently published a randomized, partially blinded trial comparing CBT to MBSR in cancer patients. Although MBSR did show a clinically significant change in sleep outcomes, CBT was associated with rapid and durable improvement, and the authors concluded that CBT remains the best nonpharmacologic therapy for this group of patients. Although intriguing, not enough evidence is available to recommend these strategies as standard interventions in cancer patients with sleep disturbances.
Combination Therapy Cognitive-behavioral therapy is at least as effective for insomnia as pharmacologic therapy.42 The initiation of medication and CBT together has been shown to be of use in insomnia, with tapering of the medication recommended as tolerated, while continuing the CBT.42 Any medication prescribed for sleep should be given at the lowest effective dose for the shortest possible duration, while more enduring interventions, such as CBT, are put in place. Benzodiazepines and nonbenzodiazepine hypnotics can be considered for short-term use in insomnia. 76,77 Other commonly prescribed sleep medications include melatonin agonists, antidepressants, and antihistamines.
Therapy for the Family Caregiver Significant sleep disturbance has been reported in the family caregivers of cancer patients as well.78,79 This may affect the daytime functional status, cognition, and quality of life of these individuals, placing the care of the oncology patient in jeopardy. Moreover, caregivers and patients are often sharing the same bed and therefore sharing one another’s sleep disruption. Cognitive-behavioral therapy intervention for caregivers has proven to benefit their sleep quality, whereas massage yielded mixed results.80,81 Studies assessing interventions of both patient and caregiver are lacking.
Exercise Exercise is used to treat other cancer-associated symptoms such as fatigue and diminished mobility. Randomized controlled trials assessing the benefit of exercise on sleep disturbance in patients with cancer have, however, yielded varying results.59–61 Cheville et al62 randomized 66 patients with either stage IV lung or colorectal cancer to usual therapy or a home-based walking and strengthening regimen. They documented improvement in sleep quality, mobility, and fatigue in the exercise group. Wenzel et al63 studied the effect of walking on 138 patients with breast, prostate, and other solid tumors. No difference in sleep quality was noted between the exercise group and those randomized to usual care. Most exercise programs entail home interventions that can be performed individually and at home. Home-based programs primarily involve walking and have proven to be difficult to assess compliance and efficacy. Studies that have looked at other modalities such as strength training and aerobics have not shown benefit. More research is needed in this area.
Complementary and Integrative Medicine A host of CIM studies have been reported evaluating techniques such as acupuncture,64 mindfulness-based stress reduction © 2014 Lippincott Williams & Wilkins
Treatment of Sleep Disorders
SUMMARY Sleep disturbances in cancer patients are common and underrecognized. Insomnia can have negative consequences on quality of life and cluster with other symptoms such as pain, fatigue, and depression. The etiologic factors of insomnia are classified as predisposing, precipitating, and perpetuating. All cancer patients should be screened for sleep disturbances. Cognitivebehavioral therapy using sleep hygiene education and behavioral modalities remains the criterion standard of nonpharmacologic therapy for insomnia in cancer patients.
Useful Highlights
• All cancer patients should be screened for insomnia and, if positive, further administered a formal assessment. • Evaluate and treat concomitant symptoms contributing to insomnia (e.g., fatigue, pain, and depression) concurrently. • Cognitive-behavioral therapy consists of redirecting negative thoughts, sleep hygiene, stimulus control, relaxation, and sleep restriction therapy, and it is at least as effective as medication. • Medications for sleep are ideally used only transiently and only in combination with more definitive therapy. www.journalppo.com
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54. Dalton JA, Keefe FJ, Carlson J, Youngblood R. Tailoring cognitivebehavioral treatment for cancer pain. Pain Manag Nurs. 2004;5:3–18. 55. Quesnel C, Savard J, Simard S, et al. Efficacy of cognitive-behavioral therapy for insomnia in women treated for nonmetastatic breast cancer. J Consult Clin Psychol. 2003;71:189–200. 56. Savard J, Villa J, Simard S, et al. Feasibility of a self-help treatment for insomnia comorbid with cancer. Psychooncology. 2011;20:1013–1019. 57. Berger AM, VonEssen S, Khun BR, et al. Feasibility of a sleep intervention during adjuvant breast cancer chemotherapy. Oncol Nurs Forum. 2002;29:1431–1441. 58. Espie CA. “Stepped care”: a health technology solution for delivering cognitive behavioral therapy as a first line insomnia treatment. Sleep. 2009;32:1549–1558. 59. Tang MF, Liou TH, Lin CC. Improving sleep quality for cancer patients: benefits of a home-based exercise intervention. Support Care Cancer. 2010;18:1329–1339. 60. Wang YJ, Boehmke M, Wu YW, et al. Effects of a 6-week walking program on Taiwanese women newly diagnosed with early-stage breast cancer. Cancer Nurs. 2011;34:E1–E13. 61. Payne JK, Held J, Thorpe J, et al. Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy. Oncol Nurs Forum. 2008;35:635–642. 62. Cheville AL, Kollasch J, Vandenberg J, et al. A home-based exercise program to improve function, fatigue, and sleep quality in patients with Stage IV lung and colorectal cancer: a randomized controlled trial. J Pain Symptom Manage. 2013;45:811–821. 63. Wenzel JA, Griffith KA, Shang J, et al. Impact of a home-based walking intervention on outcomes of sleep quality, emotional distress, and fatigue in patients undergoing treatment for solid tumors. Oncologist. 2013;18:476–484. 64. Haddad NE, Palesh O. Acupuncture in the treatment of cancer-related psychological symptoms. Integr Cancer Ther. 2014;13:371–385. 65. Garland SN, Carlson LE, Stephens AJ, et al. Mindfulness-based stress reduction compared with cognitive behavioral therapy for the treatment of insomnia comorbid with cancer: a randomized, partially blinded, noninferiority trial. J Clin Oncol. 2014;32:449–457. 66. Carlson LE, Garland SN. Impact of mindfulness-based stress reduction (MBSR) on sleep, mood, stress and fatigue symptoms in cancer outpatients. Int J Behav Med. 2005;12:278–285.
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67. Carlson LE, Speca M, Patel KD, et al. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients. Psychosom Med. 2003;65:571–581. 68. Carlson LE, Speca M, Patel KD, et al. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology. 2004;29:448–474. 69. Kvillemo P, Branstrom R. Experiences of a mindfulness-based stress-reduction intervention among patients with cancer. Cancer Nurs. 2011;34:24–31. 70. Cohen L, Warneke C, Fouladi RT, et al. Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma. Cancer. 2004;100:2253–2260. 71. Soden K, Vincent K, Craske S, et al. A randomized controlled trial of aromatherapy massage in a hospice setting. Palliat Med. 2004;18:87–92. 72. Sturgeon M, Wetta-Hall R, Hart T, et al. Effects of therapeutic massage on the quality of life among patients with breast cancer during treatment. J Altern Complement Med. 2009;15:373–380. 73. Weze C, Leathard HL, Stevens G. Evaluation of healing by gentle touch for the treatment of musculoskeletal disorders. Am J Public Health. 2004;94:50–52. 74. Pedersen CG, Christensen S, Jensen AB, et al. Faith and sleep in breast cancer: results from a nationwide Danish cohort study. Presented at the 13th World Congress of Psycho-Oncology, Antalya, Turkey; October 16–20, 2011. Conference Publication: (var.pagings). 20:49–50. 75. de Moor JS ML, Low D, et al. Expressive writing as a presurgical stress management intervention for breast cancer patients. J Soc Integr Oncol. 2008;6:59–66. 76. Minton O, Richardson A, Sharpe M, et al. A systematic review and metaanalysis of the pharmacological treatment of cancer-related fatigue. J Natl Cancer Inst. 2008;100:1155–1166. 77. Minton O, Stone P, Richardson A, et al. Drug therapy for the management of cancer related fatigue. Cochrane Database Syst Rev. 2008:CD006704. 78. Gibbins J, McCoubrie R, Kendrick AH, et al. Sleep-wake disturbances in patients with advanced cancer and their family carers. J Pain Symptom Manage. 2009;38:860–870. 79. Carter PA. Family caregivers' sleep loss and depression over time. Cancer Nurs. 2003;26:253–259. 80. Mackereth P, Sylt P, Weinberg A, Campbell G. Chair massage for carers in an acute cancer hospital. Eur J Oncol Nurs. 2005;9:167–179. 81. Carter PA. A brief behavioral sleep intervention for family caregivers of persons with cancer. Cancer Nurs. 2006;29:95–103.
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Nonpharmacologic Approach to Sleep Disorders J. Keith Mansel, MD and Elise C. Carey, MD Abstract: Sleep disturbances are common in patients with cancer, occurring throughout the disease trajectory and sometimes well after treatment has concluded. Insomnia often does not occur in isolation; it may be associated with pain, fatigue, depression, and medication usage. Screening for sleep disturbances is an essential part of caring for oncologic patients. The criterion standard for nonpharmacologic treatment of insomnia in these patients is cognitive-behavioral therapy, a multimodal approach using sleep hygiene and education, stimulus control, sleep restriction, and relaxation. Exercise and complementary and integrative medicine have been studied with varying results, and no firm recommendation can be made about their efficacy. Key Words: Cancer patients, sleep disorders, nonpharmacologic approaches, screening
other sleep-related disorders such as sleep-disordered breathing and periodic limb movements of sleep may occur.23 In this article, we provide a practical framework for evaluating and caring for cancer patients with sleep disruption and insomnia syndrome. (See also schematic in Fig. 1.) We examine the etiology of sleep disorders, including concomitant symptoms and other precipitating factors that, when treated, may improve sleep. We delineate strategies for screening patients for sleep disturbances, and we review the evidence for nonpharmacologic interventions used to treat insomnia, including sleep hygiene education, behavioral techniques, cognitive-behavioral therapy (CBT), exercise, and complementary therapies. Finally, we briefly discuss combination therapy and how sleep disturbances impact caregivers.
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leep disturbances are common among oncology patients, throughout the course of the disease and even extending into the survivor phase. Studies reveal that from 25 to 59% of oncology patients have some type of sleep disruption, which is nearly double the prevalence of the general population.1–4 Impaired sleep in patients with cancer results in worse patient-reported outcomes, including diminished quality of life, difficulty performing activities of daily living, and coping ineffectively with sleep disturbance.6,7 Higher levels of sleep disruption are often associated with other distressing symptoms in cancer patients, including fatigue, depression, and pain.8–10 Moreover, epidemiologic studies suggest that sleep disturbances are associated with an increase in cancer risk, disease progression, and poorer prognosis.12–17 Although the exact relationship is unknown, a growing body of evidence suggests that disturbed sleep may influence immune function18 and dysregulation of the circadian rhythm,19–21 which may further mediate dysregulation of the neuroendocrine system. Despite its clear impact on patient-reported quality-of-life measures and potential association with worse patient outcomes, sleep-related complaints are underreported, underrecognized, and undertreated.22 What, then, counts as sleep disturbance, and when does it require intervention? Sleep disturbance or insomnia symptoms manifest as the transient inability to either initiate or maintain sleep for a period of greater than 2 weeks, often occurring in the setting of an acute stressor. Acute insomnia can last up to 1 month and is characterized by poor quality, nonrefreshing sleep that results in poor daytime functioning. Insomnia syndrome, in contrast, is characterized as insomnia occurring more than 3 nights per week; difficulty falling asleep or nighttime awakenings (>30 minutes); poor sleep efficiency, defined as the ratio of sleep time to time spent in bed of less than 85%; and patient sense of distress and impaired daytime functioning.4 Insomnia is the most widely described sleep disturbance in cancer patients, although From the College of Medicine, Mayo Clinic, Rochester, MN. The authors have disclosed that he/she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Reprints: J. Keith Mansel, MD, Mayo Clinic, 200 First St SW, Rochester, MN. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 1528-9117
The Etiology of Insomnia: Predisposing, Precipitating, and Perpetuating Factors Spielman and Glovinsky24 have described the etiologic factors of insomnia as (1) predisposing factors, or enduring traits that increase the person’s general vulnerability to develop insomnia, (2) precipitating factors that trigger the onset of insomnia; and (3) perpetuating factors that contribute to the maintenance of insomnia over time. Factors that predispose cancer patients to insomnia include being female or having an inherent hyperarousability trait, a personal or family history of insomnia, or an anxiety or mood disorder.1,3,25–27 Interestingly, although older age predisposes to insomnia in the general population, there is some evidence that insomnia is more prevalent in younger individuals with cancer.1,25 This could be linked to high levels of psychological distress in younger patients with cancer, as well as the increased propensity for many younger women to experience menopause transition during cancer treatments.28 There are myriad factors that can precipitate sleep disturbances, including a stressful work environment, divorce, and death of a family member.29 Medical conditions and illnesses such as cancer can also precipitate insomnia, as can uncontrolled symptoms, such as pain, dyspnea, fatigue, and depression.29 Several transition points in the trajectory of illness for cancer patients may predispose for insomnia. These include the time of initial diagnosis, recurrence or progression of disease, hospitalization, and surgery.23 Inflammatory cytokines such as interleukins 1 and 6, as well as tumor necrosis factor α, may be produced by cancer cells and have some effect on the sleep-wake cycle.18 Insomnia may also be associated with chemotherapy leading to treatment associated fatigue, mood disorders, daytime napping, and alteration of circadian rhythm.4,6 In addition, medications used commonly in cancer patients such as antiemetics, steroids, and opioids can all play a role in altered sleep-wake cycles.30,31 Hormonal therapy such as antiandrogens and antiestrogens can lead to insomnia via hot flashes and night sweats.28 Perpetuating factors of insomnia in patients with cancer include maladaptive behaviors, such as spending an excessive amount of time in bed and daytime napping, and altered cognition, in which patients have unrealistic expectations of sleep and faulty perceptions of the consequences of insomnia.29 Both of these maladaptive factors may lead to heightened arousal and performance anxiety, thus worsening sleep disruption. Finally,
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FIGURE 1. Suggested screening and treatment schematic for sleep disorders.
inappropriate use of sleep aids as well as other heretofore mentioned medications can perpetuate insomnia in cancer patients.32
Screening and Assessment Given the prevalence of insomnia and sleep disturbance among cancer patients, we recommend that all cancer patients be screened for insomnia at the time of their initial visit and intermittently throughout the course of their illness (Fig. 1). Symptom clusters such as pain, fatigue, and depression, as well as the use of medications that may affect sleep, should be clues to the clinician to ask about sleep disturbances. Of note, many commonly used screening tools, including the Edmonton Symptom Assessment Score commonly used by oncologists and palliative care physicians, do not include any screening for insomnia.33 Fortunately, initial screening for insomnia need not be burdensome. Buysse et al34 recommend a 2-step process for screening and assessment of sleep disturbances, including the questions: (1) do you have problems with your sleep or sleep disturbance on average for 3 or 4 nights a week? If yes, then (2) does the problem with
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your sleep negatively impact your daytime functioning? If the answer to both questions is yes, then a more detailed assessment is warranted. Some available assessment tools include the Epworth Sleepiness Scale,5 the Insomnia Severity Index,35 and the Pittsburgh Sleep Quality Index.36
Treatment Multiple factors contribute to insomnia for any given patient, and, as such, management requires a multifaceted approach. We will be focusing on nonpharmacologic interventions for improving sleep, including the use of sleep hygiene and behavioral therapies, CBT, exercise, and complementary and integrative medicine (CIM) strategies. Because sleep disruption often does not occur in isolation in cancer patients, treatment of other symptoms such as pain and depression is paramount. Although the scope of this article is limited to nonpharmacologic treatment, medications are sometimes used on a temporary basis as a stop-gap measure, while more enduring nonpharmacologic interventions and coping strategies are put in place. © 2014 Lippincott Williams & Wilkins
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Treatment of Sleep Disorders
TABLE 1. Overview of Nonpharmacologic Treatment of Insomnia in Patients With Cancer Intervention
Objective
Sleep hygiene and behavioral interventions Education Improve factors that enhance sleep and discourage behaviors that interfere with sleep
Stimulus control
Associate the bed/bedroom with sleep
Maintain a consistent sleep-wake cycle
Sleep restriction therapy
Specifics Education about • Normal sleep • Circadian rhythm • Environmental factors affecting sleep • Go to bed only when sleep • Use the bed for sleeping only (no TV, video games, reading in bed) • Leave the bed if unable to sleep • Go to bed at the same time every night • Wake up at the same time every morning • Avoid daytime naps
Improve sleep efficiency by limiting the time in bed to the actual time spent asleep
• This is based on the theory that sleep is regulated by homeostatic and circadian mechanisms • If one is spending 9 h in bed but sleeping only 6 h, then the time in bed should be restricted to 6 h, with periodic adjustments
Reduce somatic tension and thoughts that inhibit sleep
Relaxation exercises can reduce muscle tension and redirect intrusive thoughts. Examples include the following: • Progressive muscle relaxation • Guided imagery • Meditation
Identify and change misguided and mistaken beliefs and attitudes about sleep and insomnia
• Uses psychological and cognitive methods to challenge fears • May include journaling and counseling
Relaxation training
Cognitive therapy
Cognitive-behavioral therapy Combined therapy using some or all of the above noted techniques
More than 50 studies have been performed evaluating nonpharmacologic therapy for insomnia in cancer patients, and the most elegant consist of CBT interventions.37–39 Most are not randomized controlled trials and are represented primarily by female patients, aged 51 to 55 years, and individuals with breast cancer.40 The most robust data exist for the use of sleep hygiene and CBT, and they represent the cornerstone of nonpharmacologic interventions for insomnia in patients with cancer.39 Whether the incidence and prevalence of insomnia are related to the type of cancer or the overall health status, disease, and symptom burden of the individuals has not been well elucidated in studies to date. The benefit of specifically targeting other cancer-related symptoms such as fatigue and depression remains elusive. In addition, most of the studies assessed patients months to years after the completion of therapy.40 It seems reasonable to assume that sleep disturbances may differ for patients undergoing active treatment, surgery, or radiation. The types of measures used to evaluate sleep disturbances in the available studies have proven to be highly inconsistent. Despite the number of studies of insomnia in oncologic patients, few have evaluated sleep as © 2014 Lippincott Williams & Wilkins
• Sleep hygiene education • Stimulus control • Sleep restriction • Relaxation training • Cognitive therapy
the sole primary outcome, and most do not discuss the clinical significance of the interventions studied.40 Below, we review the primary nonpharmacologic interventions recommended for sleep disruption and insomnia, including the evidence associated with each treatment. Our goal is to provide clinical guidance to clinicians caring for patients with sleep disruption. These interventions generally fall into 4 categories: (1) sleep hygiene and education including behavioral strategies, (2) CBT, (3) exercise, and (4) CIM (Table 1). There are distinct treatments within these categories, each with a varying level of evidence. Many of the interventions share commonalities, including providing education on sleep hygiene and relaxation and training patients in coping skills and cognitive reframing regarding their sleep disruption.
Sleep Hygiene and Behavioral Interventions Education about sleep hygiene, together with stimulus control, relaxation, and sleep restriction therapy, forms the basis of behavioral therapy.41 Key to treatment of sleep disturbances in patients with cancer, they have the benefit of being able to be performed in the provider’s office setting (Tables 1 and 2). www.journalppo.com
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TABLE 2. Office Tips for Helping Patients With Cancer Sleep Better Intervention
Specific Techniques
Take a sleep history
• Do you have trouble sleeping? • Does your sleep problem affect your daytime functioning? • How often do you have insomnia? • What time do you go to bed and arise, both weekdays and weekends? • What are your activities at bedtime? • What medications are you taking? • Do you use sleep aids? • Do you use stimulants such as caffeine or nicotine?
Screen for sleep disorders
• If trouble with sleep and daytime functioning, use an objective measure such as the Epworth Sleepiness Scale and a sleep diary • Screen for other sleep disorders such as obstructive sleep apnea and restless legs syndrome
Evaluate comorbid conditions and medications
• In patients with cancer • Review medications that can affect sleep such as opioids
Sleep hygiene and behavior therapy
• Maintain a consistent sleep schedule by arising and going to bed at the same time every day • Sleep as long as necessary to feel refreshed upon awakening • Do not watch TV, play video games, or worry in bed • Avoid forcing sleep • Avoid alcohol and nicotine in the evening • Limit caffeine intake to the morning • Regular exercise improves sleep quality, but avoid within several hours of bedtime • Any daytime naps should be brief and should not occur late in the day • Go to bed only when sleepy If unable to fall asleep within 20 min, leave the bedroom and return when sleepy
Some components of sleep hygiene include maintaining a consistent sleep schedule by arising and going to bed on a regular schedule, sleeping as long as necessary to feel refreshed upon awakening, avoiding stimuli near bedtime such as television, and relaxing before bedtime. Other helpful techniques include not forcing sleep, avoiding alcohol and nicotine in the evening, and limiting caffeine intake to the morning. Regular exercise, but not within several hours of bedtime, can improve sleep quality. If daytime naps are utilized, they should be brief and should not occur late in the day.32 The American Academy of Sleep Medicine recommends sleep hygiene education as an integral part of any therapy for insomnia, although there are insufficient data to suggest using this technique as standalone therapy.42 Stimulus control therapy is related to an individual’s association of the bedroom with sleep disturbance and fear of insomnia.32 This can lead to a vicious cycle, so that the longer one stays in bed, the greater the association comes. Techniques that have been proven to be useful are going to bed only when sleepy, confining the use of the bed primarily for sleeping (not watching television or checking e-mail) and, if unable to sleep within 20 minutes, getting out of bed and undertaking a relaxing pursuit such as reading.32 Activities that promote relaxation include auditory and visual biofeedback, guided imagery, progressive muscle relaxation using one muscle group at a time, and abdominal breathing to redirect thoughts to a neutral mental stance. 43 The final component of behavioral therapy for insomnia involves sleep restriction. Because some patients tend to sleep late to make up for their inability to sleep, their circadian rhythm is altered, making the initiation of sleep the following night ever the more difficult. Sleep restriction therapy aims to decrease the time spent in bed to the actual time spent in bed, often through
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the use of sleep diaries.32 For instance, if one is spending 9 hours in bed but the diary indicates the time spent asleep is 6 hours, then the time from going to bed until arising should be restricted to 6 hours. Adjustments to this can be made over time depending on the degree of sleep efficiency.
Cognitive-Behavioral Therapy Cognitive-behavioral therapy is the most well-studied nonpharmacologic intervention for insomnia in cancer patients32,44,45 and the only type of intervention noted “likely to be effective” TABLE 3. Cognitive Reframing Tips for Helping People Cope With Misconceptions About Sleep Negative thoughts (1) If I don’t sleep tonight, I will never get a restful night’s sleep. (2) If I don’t get a good night’s sleep tonight, I won’t be able to function at work tomorrow. (3) I must keep looking at the clock if I am not sleeping. (4) I can’t help that I am a worry wart. Positive thoughts (1) Tonight is just 1 night of poor sleep. (2) An occasional night of bad sleep does not mean I can’t function well the next day. (3) Looking at the clock only leads to anxiety and does not help me sleep. (4) Worrying does nothing to help me sleep. I can worry and deal with issues in the morning.
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based on the Oncology Nursing Society “Putting Evidence Into Practice” classification document.46 Cognitive-behavioral therapy is a multimodal intervention, bringing together the aforementioned sleep hygiene and behavioral techniques with cognitive therapy (Table 1). The cognitive portion of CBT involves redirecting negative or irrational thoughts about sleep. Thoughts, perceptions, and beliefs can affect physical and emotional reactions to particular situations such as the inability to initiate or maintain sleep. Negative self-talk can lead to a vicious cycle of distress and irrational thoughts regarding sleep disturbances. Cognitive therapy seeks to educate patients about positive coping skills to allay negative thinking and rumination. Table 3 lists some ways to deal with illogical beliefs, fears, and thoughts about sleep.47 More than a dozen studies have been performed evaluating CBT in insomnia in cancer patients.38–40 Most of these studies have been performed since 2000 and reveal evidence of improved sleep quality and less psychological distress. Savard et al48 studied 57 patients with breast cancer using a randomized controlled trial of CBT. They discerned improvements in sleep, depression, quality of life, anxiety, and the use of sleep aids. Importantly, these changes continued at 12-month follow-up. Espie et al49 and Berger et al50 have also performed randomized controlled trial of CBT in oncologic patients and have likewise demonstrated benefits in sleep quality and efficiency. Cognitive-behavioral therapy can be conducted in groups or individually and usually consists of several sessions. Whether 1 particular component (sleep hygiene, cognitive reframing, or behavioral interventions) is more effective than others is unknown.51 Most CBT interventions that have been studied use a standardized program, although some efforts at tailored therapies have been cited.52–55 Cognitive-behavioral therapy–trained professionals are not readily available in some areas, and an increasing number of Internet-based CBT programs are available, although more data about their efficacy are needed.56 An Individualized Sleep Promotion Plan, an adaptation of CBT for cancer-related insomnia, has recently been touted as helpful, although further work is needed.52,57 A stepped-care approach has been suggested utilizing a self-administered or Internet program initially, followed by referral to a CBT-trained professional if the original intervention proves not to be effective.58
(MBSR),9,65–69 yoga, 70massage,71,72 healing touch,73 spirituality,74 and expressive writing.75 Most of these therapies focus on negative thought patterns and redirecting irrational emotions. Studies have often been small, revealed mixed results, and did not use sleep disturbance as the primary outcome. Four clinical trials studying the benefit of acupuncture on sleep disturbance in cancer patients were recently reviewed, and some small improvements were noted.64 Garland et al65 recently published a randomized, partially blinded trial comparing CBT to MBSR in cancer patients. Although MBSR did show a clinically significant change in sleep outcomes, CBT was associated with rapid and durable improvement, and the authors concluded that CBT remains the best nonpharmacologic therapy for this group of patients. Although intriguing, not enough evidence is available to recommend these strategies as standard interventions in cancer patients with sleep disturbances.
Combination Therapy Cognitive-behavioral therapy is at least as effective for insomnia as pharmacologic therapy.42 The initiation of medication and CBT together has been shown to be of use in insomnia, with tapering of the medication recommended as tolerated, while continuing the CBT.42 Any medication prescribed for sleep should be given at the lowest effective dose for the shortest possible duration, while more enduring interventions, such as CBT, are put in place. Benzodiazepines and nonbenzodiazepine hypnotics can be considered for short-term use in insomnia. 76,77 Other commonly prescribed sleep medications include melatonin agonists, antidepressants, and antihistamines.
Therapy for the Family Caregiver Significant sleep disturbance has been reported in the family caregivers of cancer patients as well.78,79 This may affect the daytime functional status, cognition, and quality of life of these individuals, placing the care of the oncology patient in jeopardy. Moreover, caregivers and patients are often sharing the same bed and therefore sharing one another’s sleep disruption. Cognitive-behavioral therapy intervention for caregivers has proven to benefit their sleep quality, whereas massage yielded mixed results.80,81 Studies assessing interventions of both patient and caregiver are lacking.
Exercise Exercise is used to treat other cancer-associated symptoms such as fatigue and diminished mobility. Randomized controlled trials assessing the benefit of exercise on sleep disturbance in patients with cancer have, however, yielded varying results.59–61 Cheville et al62 randomized 66 patients with either stage IV lung or colorectal cancer to usual therapy or a home-based walking and strengthening regimen. They documented improvement in sleep quality, mobility, and fatigue in the exercise group. Wenzel et al63 studied the effect of walking on 138 patients with breast, prostate, and other solid tumors. No difference in sleep quality was noted between the exercise group and those randomized to usual care. Most exercise programs entail home interventions that can be performed individually and at home. Home-based programs primarily involve walking and have proven to be difficult to assess compliance and efficacy. Studies that have looked at other modalities such as strength training and aerobics have not shown benefit. More research is needed in this area.
Complementary and Integrative Medicine A host of CIM studies have been reported evaluating techniques such as acupuncture,64 mindfulness-based stress reduction © 2014 Lippincott Williams & Wilkins
Treatment of Sleep Disorders
SUMMARY Sleep disturbances in cancer patients are common and underrecognized. Insomnia can have negative consequences on quality of life and cluster with other symptoms such as pain, fatigue, and depression. The etiologic factors of insomnia are classified as predisposing, precipitating, and perpetuating. All cancer patients should be screened for sleep disturbances. Cognitivebehavioral therapy using sleep hygiene education and behavioral modalities remains the criterion standard of nonpharmacologic therapy for insomnia in cancer patients.
Useful Highlights
• All cancer patients should be screened for insomnia and, if positive, further administered a formal assessment. • Evaluate and treat concomitant symptoms contributing to insomnia (e.g., fatigue, pain, and depression) concurrently. • Cognitive-behavioral therapy consists of redirecting negative thoughts, sleep hygiene, stimulus control, relaxation, and sleep restriction therapy, and it is at least as effective as medication. • Medications for sleep are ideally used only transiently and only in combination with more definitive therapy. www.journalppo.com
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