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How do I best manage insomnia and other sleep disorders in older adults with cancer?
JGO-00354; No. of pages: 9; 4C: J O U RN A L OF GE RI A T RI C O NC O L O G Y XX ( 20 1 6 ) XX X–XX X
Available online at www.sciencedirect.com
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Geriatrics for Oncologists
How do I best manage insomnia and other sleep disorders in older adults with cancer? Kah Poh Loha,⁎, Peggy Burhennb , Arti Hurriab , Finly Zachariahb , Supriya Gupta Mohilea a
James Wilmot Cancer Institute, University of Rochester, 601 Elmwood Avenue, Box 704, Rochester, NY 14620, United States City of Hope Cancer Center, 1500 E. Duarte Road, Duarte, CA 91010, United States
b
AR TIC LE I N FO
ABS TR ACT
Article history:
Insomnia is common in older adults with cancer, with a reported prevalence of 19–60% in
Received 29 September 2015
prior studies. Cancer treatments are associated with increased risk of insomnia or
Received in revised form
aggravation of pre-existing insomnia symptoms, and patients who are receiving active
28 April 2016
cancer treatments are more likely to report insomnia. Insomnia can lead to significant
Accepted 18 May 2016
physical and psychological consequences with increased mortality. We discuss physiological sleep changes in older adults, and illustrated the various sleep disorders. We present a
Keywords:
literature review on the prevalence and the effects of insomnia on the quality of life in older
Insomnia
adults with cancer. We discuss the risk factors and presented a theoretical framework of
Prevalence
insomnia in older adults with cancer. We present a case study to illustrate the assessment
Pharmacological interventions
and management of insomnia in older adults with cancer, comparing and contrasting a
Non-pharmacological interventions
number of tools for sleep assessment. There are currently no guidelines on the treatment of sleep disorders in older adults with cancer. We present an algorithm developed at the City of Hope Comprehensive Cancer Center by a multidisciplinary team for managing insomnia, using evidence-based pharmacologic and non-pharmacologic interventions. © 2016 Elsevier Ltd. All rights reserved.
Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Case Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sleep Stages and Changes Associated with Aging and Insomnia . Prevalence of Insomnia in Older Adults with Cancer . . . . . . . . Insomnia Symptom Clusters and Risk Factors for Insomnia . . . . Effects of Insomnia on Quality of Life in Older Adults with Cancer How to Assess Insomnia in Older Adults with Cancer . . . . . . . Case Study Continued . . . . . . . . . . . . . . . . . . . . . . . . . How to Treat Older Adults with Cancer in the Outpatient Setting . Case Study Continued . . . . . . . . . . . . . . . . . . . . . . . . .
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⁎ Corresponding author at: James P. Wilmot Cancer Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, United States. Tel.: +1 413 306 9767. E-mail address: [email protected] (K.P. Loh).
http://dx.doi.org/10.1016/j.jgo.2016.05.003 1879-4068/© 2016 Elsevier Ltd. All rights reserved.
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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11. When to Refer Patients to a Specialist . . 12. Case Study Continued . . . . . . . . . . 13. Inpatient Management of Insomnia . . . 14. Conclusion . . . . . . . . . . . . . . . . Disclosures and Conflict of Interest Statements Author Contributions . . . . . . . . . . . . . . Acknowledgement . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . .
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1. Case Study Mrs. H is a 74 year-old female with metastatic breast cancer receiving trastuzumab and lapatinib on a clinical trial. During the visit with her oncologist, she reports poor sleep and is requesting a “sleeping pill”. She has difficulty with sleep initiation and stays awake until 0400 tossing and turning. Typically she will wake up and take a “Tylenol PM” (diphenhydramine) and then falls asleep until noon. She has been unable to break this cycle of poor sleep. She is frequently tired during the day and is too tired to get exercise except walking her dogs for short periods of time.
2. Introduction Insomnia is a common concern for the adult population with as many as 30% reporting difficulty sleeping.1 Older patients have a higher prevalence, ranging from 23 to 50% in prior studies.2–4 The prevalence of insomnia is also higher among patients with cancer than in the general population, and varies between 30 and 69% in studies.5–7 With the aging population and increase in life expectancy, there will be an increasing number of older adults being diagnosed with cancer.8,9 Additionally, older adults with cancer are living longer due to significant advance in cancer treatments in the recent decades. Therefore, a growing number of older survivors of cancer will suffer from insomnia. In this paper, we briefly describe the sleep stages and changes associated with aging, illustrate the prevalence, risk factors and effects of insomnia on quality of life in older adults with cancer, and recommend approaches to assess and manage sleep disorders in this population in both the outpatient and inpatient settings.
3. Sleep Stages and Changes Associated with Aging and Insomnia Adult sleep is divided into non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM). NREM sleep is divided into stage 1–4 based on characteristic electroencephalographic and electromyelographic criteria.10 With aging, overall sleep efficiency decreases, and a number of changes are seen including reductions in REM, stage 3 and 4 NREM (slow wave) sleep, decreased total sleep time and maximal sleep capacity, as well as increased nighttime arousals.10,11 In addition, aging has been linked to deterioration in the circadian function affecting the daily rhythms of wakefulness/sleep.12
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Sleep disorders are classified into insomnias, hypersomnias, circadian rhythm disorders, sleep-breathing disorders, parasomnias, and sleep movement disorders.13 Of those, insomnia is the most commonly reported sleep disorder. According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, insomnia disorder is defined as a combination of both dissatisfaction with sleep and a significant negative impact on daytime functioning.14 Dissatisfaction with sleep is further defined as difficulty initiating and/or maintaining sleep, on at least three nights per week for at least 3 months, despite adequate opportunity to sleep.14 Negative daytime impacts can include significant fatigue, sleepiness, poor concentration, low mood, or impaired ability to perform social, occupational, or caregiving responsibilities.14 In a study involving approximately 6000 older adults, difficulty maintaining sleep was the most common of insomnia symptoms.15 Sleep apnea, one of the sleep-breathing disorders, is characterized by complete cessation of respiration (apnea) and/or partial or reduced respiration (hypopnea) during sleep. Obstructive sleep apnea (OSA) is the more common form compared central sleep apnea. OSA is highly prevalent in older adults, but is often under-diagnosed.11,16 Differentiating OSA from insomnia is important given the comorbidity associated with OSA including cardiovascular diseases and neurocognitive impairment, and the availability of effective interventions such as continuous positive airway pressure for patients suffering from OSA.17,18
4. Prevalence of Insomnia in Older Adults with Cancer There are limited studies that assess the prevalence of insomnia in older adults with cancer. In three studies limited to patients with cancer who were age 65 and older, the prevalence of insomnia was found to be from 19 to 60% (Table 1).19–21 The wide variability in prevalence is likely due to the difference in the sampled population and in the methods used to assess sleep (for example, insomnia was assessed using a dichotomous response (yes/no) in the study by Mao et al., whereas Cheng et al. assessed insomnia using a Likert-scale). Patients who are receiving active cancer treatment such as in the study by Cheng et al. reported the highest prevalence of insomnia.19 Prevalence also differs by gender, age, cancer type, treatment duration, and time since cancer diagnosis. In a study of older women with breast cancer who underwent surgical treatment, distress caused by insomnia decreased significantly over time after discharge, nevertheless a significant portion of the patients reported persistent insomnia.22 Notably insomnia was found to be less
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
Study
Sample
Study type
Setting
Cancer type
Assessment
Cheng et al. 201015 Convenience Cross-sectional Oncology sample of older unit of a cancer patients regional ≥65, Mean age hospital 68.82 (SD 5.6), N = 120
Colorectal, lung, head/ neck, breast, gynecological, prostate or esophageal cancer receiving chemotherapy or radiotherapy
Chinese version of the Symptom Distress Scale (SDS-C)
Grov et al. 201011
Population Cross-sectional Population based sample based of cancer sample survivors ≥70, mean age 77.3 (SD 5.4), N = 479
At least one diagnosis of invasive cancer diagnosed >1 year before the survey, excluding non-melanoma skin cancers
Health Survey of North-Trøndelag County (HUNT-2) Survey 1995–97 Form 2 (HUNT-2)
Mao JJ et al. 200716
Population based sample of cancer survivors, ≥65 years (no median age), N = 956
Cross-sectional Population Any cancer type based sample
2002 National Health Interview Survey
Questions on insomnia
Prevalence
Other findings
This scale evaluates 10 symptoms 59.2% 20% and 29.2% of patients have including insomnia that are scored co-occurrence any two and three from 1 (no problem with a particular symptoms of pain, fatigue, symptom at the present time) to 5 insomnia, and mood disturbance. (worst possible problem). The possible 31.2% reported co-occurrence of score on insomnia ranges from 1 to 5, all of the four symptoms with 5 indicating a high level of distress. Insomnia considered if SDS-C score was ≥ 2. Two questions on insomnia: ‘Have 19.3% Prevalence same as non-cancer you had problems in getting to sleep elderly in the last month?’ and ‘During the last month, have you ever woken too early and not been able to go back to sleep?’ The rating alternatives were: ‘never’; ‘occasionally’; ‘often’ and ‘almost every night’. Insomnia considered if answers were ‘often’ or ‘almost every night’ to any of the questions. Dichotomous yes/no response 20% for 44% odds of having insomnia options: During the past 12 months males and compared to elderly non-cancer have you “. regularly had insomnia or 29% females patients. Insomnia was less trouble sleeping?” Responses of “yes” burdensome than younger were defined as insomnia survivors
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Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
Table 1 – Studies evaluating prevalence of insomnia in older adults with cancer.
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burdensome for older survivors of cancer compared to younger survivors in these studies.22
5. Insomnia Symptom Clusters and Risk Factors for Insomnia Insomnia can occur on its own, although it is often present in a cluster of symptoms along with pain, fatigue, distress, depression and anxiety.5,23–25 The relationship and interactions among these symptoms are complex; they can exacerbate each other and have synergistic effects on the functional performance of patients with cancer.26 Other risk factors have also been identified to be associated with insomnia in patients with cancer, including sociodemographic factors, underlying cancer types and stages, cancer treatments, medications and comorbid conditions.27–29 In patients undergoing cancer treatments, radiotherapy and chemotherapy were found to be associated with increased severity of insomnia.30 Hormonal treatment (i.e., androgen deprivation therapy) aggravated insomnia in patients with prostate cancer.31 Cancer treatments can exert direct effects on sleep (e.g., chemotherapy and steroids through the circadian system) and/or indirectly through their negative side-effects (e.g., nocturnal hot flashes from hormonal treatment or urinary incontinence from prostatectomy).30,32 Insomnia is commonly depicted using the theoretical framework introduced by Spielman et al., with the goal of identifying the predisposing, precipitating and perpetuating factors in insomnia.33 In older adults with cancer, aging and physiological disruption in circadian rhythms often predispose them to insomnia, which are then precipitated by cancer treatments and medications. Perpetuating factors are usually behavioral or cognitive changes that arise to cope with the acute insomnia, for example decreased physical activity and increased daytime naps.
6. Effects of Insomnia on Quality of Life in Older Adults with Cancer It is important to recognize insomnia in older adults with cancer because insomnia can be associated with significant adverse outcomes.20 In older adults with cancer, a cross-sectional study revealed that those who experience pain, fatigue, and insomnia have lower quality of life and also had the greatest decrements in functioning.34 In addition, they reported more physical and psychosocial problems.20 Studies have shown that older adults with sleep disorders are also more inclined to develop anxiety disorders and depression.35 Insomnia is also associated with impaired daytime functioning, increased risk of falls as well as problems in concentration and memory.36 Older patients with cancer who have insomnia reported 15% higher rate of musculoskeletal diseases and gastro-intestinal symptoms.20 In addition, 26% of older adults with cancer and insomnia also reported ‘good health’, which was significantly less compared to 46% in survivors without such symptoms.20 Additionally, they reported more regular use of sleep medications, problems with performing activities of daily living including personal hygiene, dressing and eating, and higher levels of anxiety and depression.20 These adverse consequences from insomnia in
turn can create challenges in cancer treatment compliance, with a higher rate of adverse events related to medication interactions and increased mortality.
7. How to Assess Insomnia in Older Adults with Cancer There is currently no gold standard to assess for sleep problems. Screening questions such as “are you sleeping well?” or “is a lack of sleep impacting your daytime activities?” can be used as a primary screen for sleep disorders. If the primary screen is positive or a patient reports insomnia additional questions to ask include: bedtime and wake times, number of hours of sleep, trouble initiating sleep or maintaining sleep, wakefulness due to other symptoms (i.e. to urinate, or pain), presence of snoring or restless legs, use of any sleep medications, and the effect the lack of sleep has had on their daytime activities. Asking a patient what they feel is contributing to their difficulty sleeping can provide insight, as worry or stress is a frequent complaint that can be addressed with non-pharmacological measures. Some available tools that can be used are the Symptom Distress Scale (SDS), which consists of a question on the presence or absence of insomnia, or the Insomnia Severity Scale, which is more comprehensive in assessing the types of sleep problems such as initiating or maintaining sleep.37 A few of the most commonly available tools are shown in Table 2. In clinical practice we have experience using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) at our centers.36,38 Other sleep disorders (such as OSA, restless leg syndrome or narcolepsy), organic disorders (hypothyroidism, depression) or medication related insomnia should be ruled out. Epworth Sleepiness Scale has been validated in the assessment of OSA, and should be used if OSA is highly suspected. A sleep study should follow if the ESS is positive. Other symptoms such as pain, fatigue, depression and anxiety should be included as part of the assessment using validated tools.
8. Case Study Continued Her oncologist has a conversation with Mrs. H about her sleep habits as well pain and mood disturbances. They discussed that all “sleeping pills” have some side effects and are particularly not advised for older adults and the preference is that she tries some non-medication efforts. The patient was not aware of side effects of diphenhydramine. Additionally, she reports watching TV in bed late at night when she cannot sleep. She had not tried any non-pharmacological remedies for sleep promotion. Mrs. H also complains of uncontrolled pain, but denies any depression or anxiety. She is taking oxycodone short-acting 5 mg every 6 h for pain.
9. How to Treat Older Adults with Cancer in the Outpatient Setting Management of insomnia includes both pharmacologic and non-pharmacologic interventions. In addition, it is important to treat the concurrent disorders such as pain, depression,
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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Table 2 – Example of tools used to assess insomnia. Tools
Description
Questions on insomnia
Symptom Distress Scale (SDS)
Assesses a range of symptoms including insomnia, pain, nausea, bowel function, fatigue, appetite, and concentration by the degree of distress the symptom is causing
Insomnia Severity Index (ISI)20
Evaluate perceived severity of insomnia and its interference with daily life
One question on insomnia is scored from 1 (no problem with a particular symptom at the present time) to 5 (worst possible problem); possible score on insomnia ranges from 1 to 5, with 5 indicating a high level of distress. Insomnia considered if SDS-C score is ≥ 2 Seven questions on insomnia that are scored from 0–4, and the answers are added up to get a total score; insomnia is present if score ≥ 8 (8–14 = subthreshold, 15–21 = moderate, 22–28 = severe) Nineteen self-rated questions that are grouped into 7 component scores, each weighted equally on a 0–3 scale and added up to get a total score. Score ≥ 5 indicates a “poor” sleeper Eight self-rated questions that are scored from 0 to 3, and are added up to get a total score; score ≥8 indicates some degree of excessive sleepiness
Assess sleep and wake times and a range of issues including nocturia, snoring, room temperature, dreams, pain, medication use, daytime activities Assess likelihood of falling asleep Scale during a range of daytime activities, validated in obstructive sleep apnea and narcolepsy
Pittsburgh Sleep Quality Index (PSQI)19
Epworth Sleepiness (ESS)21
and anxiety as they tend to co-exist in older adults with cancer.19 A number of guidelines and approaches have been developed to manage insomnia, although not specific to geriatric oncology.39,40 Fig. 1 depicts an algorithm that was developed at the City of Hope Comprehensive Cancer Center, developed by a multidisciplinary team after a synthesis and review of the literature, for the management of insomnia in older adults with cancer. We recommended two general principles: 1) use non-pharmacological measures such as sleep hygiene, sleep restriction, relaxation, and cognitive behavioral therapy first; 2) when drug therapy is utilized the risks of utilizing these agents should be discussed with the patient; and it is advised to start with the lowest dosage possible. Some routine outpatient and inpatient orders were proposed (Table 3). Non-pharmacologic interventions for sleep are generally underutilized, but should be considered as the first step in the management of insomnia. Non-pharmacologic interventions are safe and have been shown to be effective in treating insomnia, however they require a time commitment and the involvement of a multidisciplinary team.41,42 Examples of these interventions include sleep hygiene, sleep restriction, stimulus control, relaxation, and cognitive behavioral therapy.43,44 The purpose of sleep restriction is to limit the time spent in bed to the actual time sleeping therefore improving sleep efficiency, whereas sleep hygiene education aims to change patient's lifestyles to optimize sleep quality. Relaxation promotes sleep and relaxation therapies such as muscle relaxation, guided imagery, hypnosis, or massage can be used to improve sleep.45 Stimulus control therapy on the other hand helps patients to strengthen the association between sleep onset with the bed and bedroom. Finally, cognitive behavioral therapy (CBT) can help patients to identify, challenge and change negative beliefs and attitudes about sleep. A meta-analysis showed that CBT not only improves subjective outcomes, but also mood disturbance, cancer-related fatigue, and overall quality of life. Compared to pharmacological interventions, CBT will be a more attractive
Sensitivity
Specificity
—
—
86.1% (cutoff of 10)
87.7% (cutoff of 10)
89.6%
86.5%
76% (Apnea– hypopnea index of ≥5 at cutoff of 8)
31% (Apnea– hypopnea index of ≥5 at cutoff of 8)
option for older patients with cancer suffering from insomnia given the minimal side-effects.46 Exercise has also been shown to improve quality of sleep in patients with cancer.47,48 Although not specific to insomnia, the National Comprehensive Cancer Network Guidelines recommend that patients initiate the exercise program at a low level of intensity and duration, progress slowly and modify the program as conditions change.49 Most providers use pharmacologic agents as their first choice for insomnia. Examples of commonly prescribed sleep medications include non-benzodiazepine hypnotics such as eszopiclone and zolpidem, benzodiazepine such as temazepam, antidepressants such as trazodone, antihistamines such as hydroxyzine and diphenhydramine, or melatonin or the melatonin receptor agonist ramelteon. However most of these medications are on the American Geriatrics Society (AGS) Beers Criteria for potentially inappropriate medication use in older adults given the side-effects associated with these medications (e.g. benzodiazepines are associated cognitive impairment, increased risk of falls and fractures; antihistamines are associated with anticholinergic effects such as confusion, constipation and urinary retention); therefore there are challenges to safe prescribing of sleep medications in this population.50
10. Case Study Continued After a review of Mrs. H′s daily routine and lifestyle, the following recommendations were made: 1) Improve sleep hygiene: Only go to bed when sleepy, maintain a consistent bedtime and wake up time, no TV late at night (turn off TV 1–2 h before bedtime), get up if not falling asleep and do something until you feel sleepy. 2) Increase exercise: Mrs. H agreed that she could take longer walks with the dogs.
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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The oncologist also reinforced relaxation strategies and exercise along with additional sleep hygiene recommendations, such as a light protein snack at night and the importance of a developing a consistent routine. A patient education handout with tips (supplemental appendix Table 1) for sleep promotion was given to the
patient. The oncologist also prescribed oxycontin long-acting 12 mg every 12 h in addition to oxycodone for better pain control. At the next clinic visit 3 weeks later, Mrs. H reported that she had implemented our suggestions and her sleep was better. Her pain was better controlled. She had discontinued the use of
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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Table 3 – General routine orders for insomnia in the outpatient and inpatient settings.
Table 4 – Pharmacologic interventions for treatment of insomnia.
Inpatient and outpatient orders Provide patients with the educational handout on insomnia Ensure adequate bed covers for warmth Encourage regular bedtime and wake times Discourage stimulating exercise and heavy meals within 2 h of bedtime Encourage patients to lie flat (if tolerated) and turn off TVs, computers, and other electronics one hour before bedtime Keep rooms light during the day and dark at night Suggest the regulation of fluid intake and reduction in caffeine prior to bedtime Encourage bowel and bladder elimination prior to sleep Encourage family members to provide back rubs and/or massage for comfort Keep skin clean and dry Inpatient-specific orders Provide guided imagery recordings available on closed circuit television (CCTV) for inpatients Minimize and coordinate necessary bedside contacts overnight for inpatients [organize care; i.e. registered nurse (RN) and patient care assistant (PCA) go in together] Use a condom catheter for nocturnal incontinence in males, as appropriate
First Tier Melatonin 3 mg orally at bedtime as needed for insomnia Temazepam 7.5 mg orally at bedtime as needed for insomnia Zolpidem 5 mg orally at bedtime as needed for insomnia (use with caution in the older adult) Second Tier, if insomnia persists after 2 nights at above dose, consider higher dose or switch to other agents below: Melatonin 5 mg orally at bedtime as needed for insomnia Temazepam 15 mg orally at bedtime as needed for insomnia (use with caution in the older or medically frail patient) Zolpidem 10 mg orally at bedtime as needed for insomnia [Federal and Drug Administration (FDA) Alert regarding 10 mg dose, discuss risk/benefit with patient before ordering] Or Switch to: Ramelteon 8 mg orally at bedtime as needed for insomnia Trazodone 25 mg orally at bedtime as needed for insomnia
diphenhydramine. She was wondering if she should see a specialist.
11. When to Refer Patients to a Specialist Referral to specialists depends on oncologists' comfort level, but patients who have not responded to non-pharmacologic interventions with persistent insomnia on multiple sleep medications should be referred to a sleep specialist. It is important to involve the patients' primary care physicians in the management of insomnia. If the patients are interested in CBT programs, they should be referred to see a psychologists or behavioral sleep medicine specialists. If there is a high suspicion for OSA or other primary sleep disorders, referral to sleep medicine specialists or pulmonologists should also be considered.
12. Case Study Continued Mrs. H was admitted three months later due to pneumonia. Her family was concerned that she was not sleeping in the hospital and was progressively getting more confused. Her primary team prescribed melatonin 3 mg to help with her insomnia, and also instituted a
number of non-pharmacologic orders (Table 3). The following day, she was sleeping better.
13. Inpatient Management of Insomnia Older patients with cancer undergoing treatments are more likely to experience complications and adverse events from their cancer and cancer treatment, often requiring hospitalizations.51 Managing older adults with cancer in the hospital is complex due to frequent co-existing comorbidities and polypharmacy, requiring recurring visits from various healthcare professionals with frequent interruptions, which can often precipitate insomnia. Their increased sensitivity to environmental changes can also exacerbate their insomnia (such as increased anxiety with unfamiliar environment). Although the management of insomnia in the inpatient is similar to the outpatient setting, a number of inpatient-specific non-pharmacologic interventions can be instituted, as shown in Table 3.
14. Conclusion Older adults with cancer are at risk for insomnia. Insomnia can impact quality of life and lead to daytime fatigue. Many pharmaceuticals approved for insomnia are high-risk choices for older adults. Non-pharmacological methods of promoting sleep are effective in managing insomnia and should be used first line in older adults. An organized teaching plan with patient instructions can assist in minimizing or eliminating the use of drugs for sleep promotion and improve patient satisfaction with sleep quality.
Fig. 1 – Algorithm in the management of insomnia in older adults with cancer. The algorithm is developed by a multidisciplinary team consisting of healthcare professionals in medical oncology, palliative care, psychiatry, psychology, pharmacy, and nursing at the City of Hope Comprehensive Cancer Center. The multidisciplinary team reviewed and synthesized relevant literature (27 key journal articles and American Geriatric Society [AGS] guidelines) to identify evidence-based interventions for insomnia. Based on this review the expert panel worked to develop a consensus and recommendations for non-pharmacological as well as pharmacological options for insomnia, including special considerations for older adults. OSA: Obstructive sleep apnea; COPD: Chronic obstructive pulmonary disease; CHF: Congestive heart failure; GERD: Gastroesophageal reflux disorder; ESS: Epworth Sleepiness Scale; PSQI: Pittsburgh Sleep Quality Index; ISI: Insomnia Severity Scale. (See Tables 3 and 4.) Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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Disclosures and Conflict of Interest Statements The authors have no conflict of interest to report.
Author Contributions Quality control of data and algorithms: KP Loh, P Burhenn. Manuscript preparation: KP Loh, P Burhenn. Manuscript editing: A Hurria, F Zachariah, SG Mohile. Manuscript review: KP Loh, P Burhenn, A Hurria, F Zachariah, SG Mohile.
Acknowledgement We would like to acknowledge the following members on the multidisciplinary team who were involved in developing the algorithm: Peggy Burhenn, MS, CNS, AOCNS; Arti Hurria, MD; Finly Zachariah, MD; Sorin Buga, MD; Stephanie Davidson, PsyD; Carl Kildoo, PharmD; Yvette McLin, MD; Sepideh Shayani, PharmD and Carin van Zyl, MD.
REFERENCES
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12. Kondratova AA, Kondratov RV. The circadian clock and pathology of the ageing brain. Nat Rev Neurosci May 2012;13(5): 325–335. 13. American Academy of Sleep Medicine. International Classification of Sleep Disorders—3rd edition (ICSD-3); 2014. 14. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington: American Psychiatric Association; 2013. 15. Jaussent I, Dauvilliers Y, Ancelin M-L, Dartigues J-F, Tavernier B, Touchon J, et al. Insomnia symptoms in older adults: associated factors and gender differences. Am J Geriatr Psychiatry Jan 2011;19(1):88–97. 16. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Sleep-disordered breathing in community-dwelling elderly. Sleep Dec 1991;14(6):486–495. 17. Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea. Chest Jun 2012;141(6):1601–1610. 18. Hersi AS. Obstructive sleep apnea and cardiac arrhythmias. Ann Thorac Med 2010;5(1):10–17. 19. Cheng KKF, Lee DTF. Effects of pain, fatigue, insomnia, and mood disturbance on functional status and quality of life of elderly patients with cancer. Crit Rev Oncol Hematol May 2011;78(2):127–137. 20. Grov EK, Fosså SD, Dahl AA. Insomnia in elderly cancer survivors—a population-based controlled study of associations with lifestyle, morbidity, and psychosocial factors. Results from the Health Survey of North-Trøndelag County (HUNT-2). Insomnia in elderly cancer survivors. Support Care Cancer Off J Multinatl Assoc Support Care Cancer Sep 2011;19(9):1319–1326. 21. Mao JJ, Armstrong K, Bowman MA, Xie SX, Kadakia R, Farrar JT. Symptom burden among cancer survivors: impact of age and comorbidity. J Am Board Fam Med Oct 2007;20(5):434–443. 22. Kenefick AL. Patterns of symptom distress in older women after surgical treatment for breast cancer. Oncol Nurs Forum Mar 2006;33(2):327–335. 23. Kozachik SL, Bandeen-Roche K. Predictors of patterns of pain, fatigue and insomnia during the first year following a cancer diagnosis in the elderly. Cancer Nurs 2008;31(5):334–344. 24. Dirksen SR, Epstein DR, Hoyt MA. Insomnia, depression, and distress among outpatients with prostate cancer. Appl Nurs Res 2009 Aug;22(3):154–158. 25. Desai MM, Zhang P, Hennessy CH. Surveillance for morbidity and mortality among older adults—United States, 1995–1996. MMWR CDC Surveill Summ Morb Mortal Wkly Rep CDC Surveill Summ Cent Dis Control Dec 17 1999;48(8):7–25. 26. Oh H, Seo Y, Jeong H, Seo W. The identification of multiple symptom clusters and their effects on functional performance in cancer patients. J Clin Nurs 2012 Oct;21(19–20):2832–2842. 27. Morris BA, Thorndike FP, Ritterband LM, Glozier N, Dunn J, Chambers SK. Sleep disturbance in cancer patients and caregivers who contact telephone-based help services. Support Care Cancer Off J Multinatl Assoc Support Care Cancer Apr 2015;23(4):1113–1120. 28. Thomas BC, Waller A, Malhi RL, Fung T, Carlson LE, Groff SL, et al. A longitudinal analysis of symptom clusters in cancer patients and their sociodemographic predictors. J Pain Symptom Manage Mar 2014;47(3):566–578. 29. O'Donnell JF. Insomnia in cancer patients. Clin Cornerstone 2004;6(Suppl 1D):S6–14. 30. Savard J, Ivers H, Savard M-H, Morin CM. Cancer treatments and their side effects are associated with aggravation of insomnia: results of a longitudinal study. Cancer May 15 2015;121(10):1703–1711. 31. Savard J, Hervouet S, Ivers H. Prostate cancer treatments and their side effects are associated with increased insomnia. Psychooncology 2013 Jun;22(6):1381–1388. 32. Savard J, Liu L, Natarajan L, Rissling MB, Neikrug AB, He F, et al. Breast cancer patients have progressively impaired
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43. Petit L, Azad N, Byszewski A, Sarazan FF-A, Power B. Non-pharmacological management of primary and secondary insomnia among older people: review of assessment tools and treatments. Age Ageing Jan 2003;32(1):19–25. 44. Dahiya S, Ahluwalia MS, Walia HK. Sleep disturbances in cancer patients: underrecognized and undertreated. Cleve Clin J Med Nov 2013;80(11):722–732. 45. Lareau R, Benson L, Watcharotone K, Manguba G. Examining the feasibility of implementing specific nursing interventions to promote sleep in hospitalized elderly patients. Geriatr Nurs (N Y N) Jun 2008;29(3):197–206. 46. Garland SN, Johnson JA, Savard J, Gehrman P, Perlis M, Carlson L, et al. Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Neuropsychiatr Dis Treat Jun 18 2014;10: 1113–1124. 47. Chiu H-Y, Huang H-C, Chen P-Y, Hou W-H, Tsai P-S. Walking improves sleep in individuals with cancer: a meta-analysis of randomized, controlled trials. Oncol Nurs Forum Mar 2015;42(2): E54–E62. 48. Sharif F, Seddigh M, Jahanbin I, Keshavarzi S. The effect of aerobic exercise on quantity and quality of sleep among elderly people referring to health centers of Lar City, Southern of Iran; a randomized controlled clinical trial. Curr Aging Sci 2015;8(3):248–255. 49. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Cancer-related fatigue, version 1.2016. Available at: http://www.nccn.org/professionals/ physician_gls/pdf/fatigue.pdf [Accessed 07 February 16]. 50. Campanelli CM. American Geriatrics Society updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc Apr 2012;60(4):616–631. 51. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol Off J Am Soc Clin Oncol Sep 1 2011;29(25):3457–3465.
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
Available online at www.sciencedirect.com
ScienceDirect
Geriatrics for Oncologists
How do I best manage insomnia and other sleep disorders in older adults with cancer? Kah Poh Loha,⁎, Peggy Burhennb , Arti Hurriab , Finly Zachariahb , Supriya Gupta Mohilea a
James Wilmot Cancer Institute, University of Rochester, 601 Elmwood Avenue, Box 704, Rochester, NY 14620, United States City of Hope Cancer Center, 1500 E. Duarte Road, Duarte, CA 91010, United States
b
AR TIC LE I N FO
ABS TR ACT
Article history:
Insomnia is common in older adults with cancer, with a reported prevalence of 19–60% in
Received 29 September 2015
prior studies. Cancer treatments are associated with increased risk of insomnia or
Received in revised form
aggravation of pre-existing insomnia symptoms, and patients who are receiving active
28 April 2016
cancer treatments are more likely to report insomnia. Insomnia can lead to significant
Accepted 18 May 2016
physical and psychological consequences with increased mortality. We discuss physiological sleep changes in older adults, and illustrated the various sleep disorders. We present a
Keywords:
literature review on the prevalence and the effects of insomnia on the quality of life in older
Insomnia
adults with cancer. We discuss the risk factors and presented a theoretical framework of
Prevalence
insomnia in older adults with cancer. We present a case study to illustrate the assessment
Pharmacological interventions
and management of insomnia in older adults with cancer, comparing and contrasting a
Non-pharmacological interventions
number of tools for sleep assessment. There are currently no guidelines on the treatment of sleep disorders in older adults with cancer. We present an algorithm developed at the City of Hope Comprehensive Cancer Center by a multidisciplinary team for managing insomnia, using evidence-based pharmacologic and non-pharmacologic interventions. © 2016 Elsevier Ltd. All rights reserved.
Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Case Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sleep Stages and Changes Associated with Aging and Insomnia . Prevalence of Insomnia in Older Adults with Cancer . . . . . . . . Insomnia Symptom Clusters and Risk Factors for Insomnia . . . . Effects of Insomnia on Quality of Life in Older Adults with Cancer How to Assess Insomnia in Older Adults with Cancer . . . . . . . Case Study Continued . . . . . . . . . . . . . . . . . . . . . . . . . How to Treat Older Adults with Cancer in the Outpatient Setting . Case Study Continued . . . . . . . . . . . . . . . . . . . . . . . . .
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⁎ Corresponding author at: James P. Wilmot Cancer Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, United States. Tel.: +1 413 306 9767. E-mail address: [email protected] (K.P. Loh).
http://dx.doi.org/10.1016/j.jgo.2016.05.003 1879-4068/© 2016 Elsevier Ltd. All rights reserved.
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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11. When to Refer Patients to a Specialist . . 12. Case Study Continued . . . . . . . . . . 13. Inpatient Management of Insomnia . . . 14. Conclusion . . . . . . . . . . . . . . . . Disclosures and Conflict of Interest Statements Author Contributions . . . . . . . . . . . . . . Acknowledgement . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . .
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1. Case Study Mrs. H is a 74 year-old female with metastatic breast cancer receiving trastuzumab and lapatinib on a clinical trial. During the visit with her oncologist, she reports poor sleep and is requesting a “sleeping pill”. She has difficulty with sleep initiation and stays awake until 0400 tossing and turning. Typically she will wake up and take a “Tylenol PM” (diphenhydramine) and then falls asleep until noon. She has been unable to break this cycle of poor sleep. She is frequently tired during the day and is too tired to get exercise except walking her dogs for short periods of time.
2. Introduction Insomnia is a common concern for the adult population with as many as 30% reporting difficulty sleeping.1 Older patients have a higher prevalence, ranging from 23 to 50% in prior studies.2–4 The prevalence of insomnia is also higher among patients with cancer than in the general population, and varies between 30 and 69% in studies.5–7 With the aging population and increase in life expectancy, there will be an increasing number of older adults being diagnosed with cancer.8,9 Additionally, older adults with cancer are living longer due to significant advance in cancer treatments in the recent decades. Therefore, a growing number of older survivors of cancer will suffer from insomnia. In this paper, we briefly describe the sleep stages and changes associated with aging, illustrate the prevalence, risk factors and effects of insomnia on quality of life in older adults with cancer, and recommend approaches to assess and manage sleep disorders in this population in both the outpatient and inpatient settings.
3. Sleep Stages and Changes Associated with Aging and Insomnia Adult sleep is divided into non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM). NREM sleep is divided into stage 1–4 based on characteristic electroencephalographic and electromyelographic criteria.10 With aging, overall sleep efficiency decreases, and a number of changes are seen including reductions in REM, stage 3 and 4 NREM (slow wave) sleep, decreased total sleep time and maximal sleep capacity, as well as increased nighttime arousals.10,11 In addition, aging has been linked to deterioration in the circadian function affecting the daily rhythms of wakefulness/sleep.12
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Sleep disorders are classified into insomnias, hypersomnias, circadian rhythm disorders, sleep-breathing disorders, parasomnias, and sleep movement disorders.13 Of those, insomnia is the most commonly reported sleep disorder. According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, insomnia disorder is defined as a combination of both dissatisfaction with sleep and a significant negative impact on daytime functioning.14 Dissatisfaction with sleep is further defined as difficulty initiating and/or maintaining sleep, on at least three nights per week for at least 3 months, despite adequate opportunity to sleep.14 Negative daytime impacts can include significant fatigue, sleepiness, poor concentration, low mood, or impaired ability to perform social, occupational, or caregiving responsibilities.14 In a study involving approximately 6000 older adults, difficulty maintaining sleep was the most common of insomnia symptoms.15 Sleep apnea, one of the sleep-breathing disorders, is characterized by complete cessation of respiration (apnea) and/or partial or reduced respiration (hypopnea) during sleep. Obstructive sleep apnea (OSA) is the more common form compared central sleep apnea. OSA is highly prevalent in older adults, but is often under-diagnosed.11,16 Differentiating OSA from insomnia is important given the comorbidity associated with OSA including cardiovascular diseases and neurocognitive impairment, and the availability of effective interventions such as continuous positive airway pressure for patients suffering from OSA.17,18
4. Prevalence of Insomnia in Older Adults with Cancer There are limited studies that assess the prevalence of insomnia in older adults with cancer. In three studies limited to patients with cancer who were age 65 and older, the prevalence of insomnia was found to be from 19 to 60% (Table 1).19–21 The wide variability in prevalence is likely due to the difference in the sampled population and in the methods used to assess sleep (for example, insomnia was assessed using a dichotomous response (yes/no) in the study by Mao et al., whereas Cheng et al. assessed insomnia using a Likert-scale). Patients who are receiving active cancer treatment such as in the study by Cheng et al. reported the highest prevalence of insomnia.19 Prevalence also differs by gender, age, cancer type, treatment duration, and time since cancer diagnosis. In a study of older women with breast cancer who underwent surgical treatment, distress caused by insomnia decreased significantly over time after discharge, nevertheless a significant portion of the patients reported persistent insomnia.22 Notably insomnia was found to be less
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
Study
Sample
Study type
Setting
Cancer type
Assessment
Cheng et al. 201015 Convenience Cross-sectional Oncology sample of older unit of a cancer patients regional ≥65, Mean age hospital 68.82 (SD 5.6), N = 120
Colorectal, lung, head/ neck, breast, gynecological, prostate or esophageal cancer receiving chemotherapy or radiotherapy
Chinese version of the Symptom Distress Scale (SDS-C)
Grov et al. 201011
Population Cross-sectional Population based sample based of cancer sample survivors ≥70, mean age 77.3 (SD 5.4), N = 479
At least one diagnosis of invasive cancer diagnosed >1 year before the survey, excluding non-melanoma skin cancers
Health Survey of North-Trøndelag County (HUNT-2) Survey 1995–97 Form 2 (HUNT-2)
Mao JJ et al. 200716
Population based sample of cancer survivors, ≥65 years (no median age), N = 956
Cross-sectional Population Any cancer type based sample
2002 National Health Interview Survey
Questions on insomnia
Prevalence
Other findings
This scale evaluates 10 symptoms 59.2% 20% and 29.2% of patients have including insomnia that are scored co-occurrence any two and three from 1 (no problem with a particular symptoms of pain, fatigue, symptom at the present time) to 5 insomnia, and mood disturbance. (worst possible problem). The possible 31.2% reported co-occurrence of score on insomnia ranges from 1 to 5, all of the four symptoms with 5 indicating a high level of distress. Insomnia considered if SDS-C score was ≥ 2. Two questions on insomnia: ‘Have 19.3% Prevalence same as non-cancer you had problems in getting to sleep elderly in the last month?’ and ‘During the last month, have you ever woken too early and not been able to go back to sleep?’ The rating alternatives were: ‘never’; ‘occasionally’; ‘often’ and ‘almost every night’. Insomnia considered if answers were ‘often’ or ‘almost every night’ to any of the questions. Dichotomous yes/no response 20% for 44% odds of having insomnia options: During the past 12 months males and compared to elderly non-cancer have you “. regularly had insomnia or 29% females patients. Insomnia was less trouble sleeping?” Responses of “yes” burdensome than younger were defined as insomnia survivors
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Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
Table 1 – Studies evaluating prevalence of insomnia in older adults with cancer.
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burdensome for older survivors of cancer compared to younger survivors in these studies.22
5. Insomnia Symptom Clusters and Risk Factors for Insomnia Insomnia can occur on its own, although it is often present in a cluster of symptoms along with pain, fatigue, distress, depression and anxiety.5,23–25 The relationship and interactions among these symptoms are complex; they can exacerbate each other and have synergistic effects on the functional performance of patients with cancer.26 Other risk factors have also been identified to be associated with insomnia in patients with cancer, including sociodemographic factors, underlying cancer types and stages, cancer treatments, medications and comorbid conditions.27–29 In patients undergoing cancer treatments, radiotherapy and chemotherapy were found to be associated with increased severity of insomnia.30 Hormonal treatment (i.e., androgen deprivation therapy) aggravated insomnia in patients with prostate cancer.31 Cancer treatments can exert direct effects on sleep (e.g., chemotherapy and steroids through the circadian system) and/or indirectly through their negative side-effects (e.g., nocturnal hot flashes from hormonal treatment or urinary incontinence from prostatectomy).30,32 Insomnia is commonly depicted using the theoretical framework introduced by Spielman et al., with the goal of identifying the predisposing, precipitating and perpetuating factors in insomnia.33 In older adults with cancer, aging and physiological disruption in circadian rhythms often predispose them to insomnia, which are then precipitated by cancer treatments and medications. Perpetuating factors are usually behavioral or cognitive changes that arise to cope with the acute insomnia, for example decreased physical activity and increased daytime naps.
6. Effects of Insomnia on Quality of Life in Older Adults with Cancer It is important to recognize insomnia in older adults with cancer because insomnia can be associated with significant adverse outcomes.20 In older adults with cancer, a cross-sectional study revealed that those who experience pain, fatigue, and insomnia have lower quality of life and also had the greatest decrements in functioning.34 In addition, they reported more physical and psychosocial problems.20 Studies have shown that older adults with sleep disorders are also more inclined to develop anxiety disorders and depression.35 Insomnia is also associated with impaired daytime functioning, increased risk of falls as well as problems in concentration and memory.36 Older patients with cancer who have insomnia reported 15% higher rate of musculoskeletal diseases and gastro-intestinal symptoms.20 In addition, 26% of older adults with cancer and insomnia also reported ‘good health’, which was significantly less compared to 46% in survivors without such symptoms.20 Additionally, they reported more regular use of sleep medications, problems with performing activities of daily living including personal hygiene, dressing and eating, and higher levels of anxiety and depression.20 These adverse consequences from insomnia in
turn can create challenges in cancer treatment compliance, with a higher rate of adverse events related to medication interactions and increased mortality.
7. How to Assess Insomnia in Older Adults with Cancer There is currently no gold standard to assess for sleep problems. Screening questions such as “are you sleeping well?” or “is a lack of sleep impacting your daytime activities?” can be used as a primary screen for sleep disorders. If the primary screen is positive or a patient reports insomnia additional questions to ask include: bedtime and wake times, number of hours of sleep, trouble initiating sleep or maintaining sleep, wakefulness due to other symptoms (i.e. to urinate, or pain), presence of snoring or restless legs, use of any sleep medications, and the effect the lack of sleep has had on their daytime activities. Asking a patient what they feel is contributing to their difficulty sleeping can provide insight, as worry or stress is a frequent complaint that can be addressed with non-pharmacological measures. Some available tools that can be used are the Symptom Distress Scale (SDS), which consists of a question on the presence or absence of insomnia, or the Insomnia Severity Scale, which is more comprehensive in assessing the types of sleep problems such as initiating or maintaining sleep.37 A few of the most commonly available tools are shown in Table 2. In clinical practice we have experience using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) at our centers.36,38 Other sleep disorders (such as OSA, restless leg syndrome or narcolepsy), organic disorders (hypothyroidism, depression) or medication related insomnia should be ruled out. Epworth Sleepiness Scale has been validated in the assessment of OSA, and should be used if OSA is highly suspected. A sleep study should follow if the ESS is positive. Other symptoms such as pain, fatigue, depression and anxiety should be included as part of the assessment using validated tools.
8. Case Study Continued Her oncologist has a conversation with Mrs. H about her sleep habits as well pain and mood disturbances. They discussed that all “sleeping pills” have some side effects and are particularly not advised for older adults and the preference is that she tries some non-medication efforts. The patient was not aware of side effects of diphenhydramine. Additionally, she reports watching TV in bed late at night when she cannot sleep. She had not tried any non-pharmacological remedies for sleep promotion. Mrs. H also complains of uncontrolled pain, but denies any depression or anxiety. She is taking oxycodone short-acting 5 mg every 6 h for pain.
9. How to Treat Older Adults with Cancer in the Outpatient Setting Management of insomnia includes both pharmacologic and non-pharmacologic interventions. In addition, it is important to treat the concurrent disorders such as pain, depression,
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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Table 2 – Example of tools used to assess insomnia. Tools
Description
Questions on insomnia
Symptom Distress Scale (SDS)
Assesses a range of symptoms including insomnia, pain, nausea, bowel function, fatigue, appetite, and concentration by the degree of distress the symptom is causing
Insomnia Severity Index (ISI)20
Evaluate perceived severity of insomnia and its interference with daily life
One question on insomnia is scored from 1 (no problem with a particular symptom at the present time) to 5 (worst possible problem); possible score on insomnia ranges from 1 to 5, with 5 indicating a high level of distress. Insomnia considered if SDS-C score is ≥ 2 Seven questions on insomnia that are scored from 0–4, and the answers are added up to get a total score; insomnia is present if score ≥ 8 (8–14 = subthreshold, 15–21 = moderate, 22–28 = severe) Nineteen self-rated questions that are grouped into 7 component scores, each weighted equally on a 0–3 scale and added up to get a total score. Score ≥ 5 indicates a “poor” sleeper Eight self-rated questions that are scored from 0 to 3, and are added up to get a total score; score ≥8 indicates some degree of excessive sleepiness
Assess sleep and wake times and a range of issues including nocturia, snoring, room temperature, dreams, pain, medication use, daytime activities Assess likelihood of falling asleep Scale during a range of daytime activities, validated in obstructive sleep apnea and narcolepsy
Pittsburgh Sleep Quality Index (PSQI)19
Epworth Sleepiness (ESS)21
and anxiety as they tend to co-exist in older adults with cancer.19 A number of guidelines and approaches have been developed to manage insomnia, although not specific to geriatric oncology.39,40 Fig. 1 depicts an algorithm that was developed at the City of Hope Comprehensive Cancer Center, developed by a multidisciplinary team after a synthesis and review of the literature, for the management of insomnia in older adults with cancer. We recommended two general principles: 1) use non-pharmacological measures such as sleep hygiene, sleep restriction, relaxation, and cognitive behavioral therapy first; 2) when drug therapy is utilized the risks of utilizing these agents should be discussed with the patient; and it is advised to start with the lowest dosage possible. Some routine outpatient and inpatient orders were proposed (Table 3). Non-pharmacologic interventions for sleep are generally underutilized, but should be considered as the first step in the management of insomnia. Non-pharmacologic interventions are safe and have been shown to be effective in treating insomnia, however they require a time commitment and the involvement of a multidisciplinary team.41,42 Examples of these interventions include sleep hygiene, sleep restriction, stimulus control, relaxation, and cognitive behavioral therapy.43,44 The purpose of sleep restriction is to limit the time spent in bed to the actual time sleeping therefore improving sleep efficiency, whereas sleep hygiene education aims to change patient's lifestyles to optimize sleep quality. Relaxation promotes sleep and relaxation therapies such as muscle relaxation, guided imagery, hypnosis, or massage can be used to improve sleep.45 Stimulus control therapy on the other hand helps patients to strengthen the association between sleep onset with the bed and bedroom. Finally, cognitive behavioral therapy (CBT) can help patients to identify, challenge and change negative beliefs and attitudes about sleep. A meta-analysis showed that CBT not only improves subjective outcomes, but also mood disturbance, cancer-related fatigue, and overall quality of life. Compared to pharmacological interventions, CBT will be a more attractive
Sensitivity
Specificity
—
—
86.1% (cutoff of 10)
87.7% (cutoff of 10)
89.6%
86.5%
76% (Apnea– hypopnea index of ≥5 at cutoff of 8)
31% (Apnea– hypopnea index of ≥5 at cutoff of 8)
option for older patients with cancer suffering from insomnia given the minimal side-effects.46 Exercise has also been shown to improve quality of sleep in patients with cancer.47,48 Although not specific to insomnia, the National Comprehensive Cancer Network Guidelines recommend that patients initiate the exercise program at a low level of intensity and duration, progress slowly and modify the program as conditions change.49 Most providers use pharmacologic agents as their first choice for insomnia. Examples of commonly prescribed sleep medications include non-benzodiazepine hypnotics such as eszopiclone and zolpidem, benzodiazepine such as temazepam, antidepressants such as trazodone, antihistamines such as hydroxyzine and diphenhydramine, or melatonin or the melatonin receptor agonist ramelteon. However most of these medications are on the American Geriatrics Society (AGS) Beers Criteria for potentially inappropriate medication use in older adults given the side-effects associated with these medications (e.g. benzodiazepines are associated cognitive impairment, increased risk of falls and fractures; antihistamines are associated with anticholinergic effects such as confusion, constipation and urinary retention); therefore there are challenges to safe prescribing of sleep medications in this population.50
10. Case Study Continued After a review of Mrs. H′s daily routine and lifestyle, the following recommendations were made: 1) Improve sleep hygiene: Only go to bed when sleepy, maintain a consistent bedtime and wake up time, no TV late at night (turn off TV 1–2 h before bedtime), get up if not falling asleep and do something until you feel sleepy. 2) Increase exercise: Mrs. H agreed that she could take longer walks with the dogs.
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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The oncologist also reinforced relaxation strategies and exercise along with additional sleep hygiene recommendations, such as a light protein snack at night and the importance of a developing a consistent routine. A patient education handout with tips (supplemental appendix Table 1) for sleep promotion was given to the
patient. The oncologist also prescribed oxycontin long-acting 12 mg every 12 h in addition to oxycodone for better pain control. At the next clinic visit 3 weeks later, Mrs. H reported that she had implemented our suggestions and her sleep was better. Her pain was better controlled. She had discontinued the use of
Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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Table 3 – General routine orders for insomnia in the outpatient and inpatient settings.
Table 4 – Pharmacologic interventions for treatment of insomnia.
Inpatient and outpatient orders Provide patients with the educational handout on insomnia Ensure adequate bed covers for warmth Encourage regular bedtime and wake times Discourage stimulating exercise and heavy meals within 2 h of bedtime Encourage patients to lie flat (if tolerated) and turn off TVs, computers, and other electronics one hour before bedtime Keep rooms light during the day and dark at night Suggest the regulation of fluid intake and reduction in caffeine prior to bedtime Encourage bowel and bladder elimination prior to sleep Encourage family members to provide back rubs and/or massage for comfort Keep skin clean and dry Inpatient-specific orders Provide guided imagery recordings available on closed circuit television (CCTV) for inpatients Minimize and coordinate necessary bedside contacts overnight for inpatients [organize care; i.e. registered nurse (RN) and patient care assistant (PCA) go in together] Use a condom catheter for nocturnal incontinence in males, as appropriate
First Tier Melatonin 3 mg orally at bedtime as needed for insomnia Temazepam 7.5 mg orally at bedtime as needed for insomnia Zolpidem 5 mg orally at bedtime as needed for insomnia (use with caution in the older adult) Second Tier, if insomnia persists after 2 nights at above dose, consider higher dose or switch to other agents below: Melatonin 5 mg orally at bedtime as needed for insomnia Temazepam 15 mg orally at bedtime as needed for insomnia (use with caution in the older or medically frail patient) Zolpidem 10 mg orally at bedtime as needed for insomnia [Federal and Drug Administration (FDA) Alert regarding 10 mg dose, discuss risk/benefit with patient before ordering] Or Switch to: Ramelteon 8 mg orally at bedtime as needed for insomnia Trazodone 25 mg orally at bedtime as needed for insomnia
diphenhydramine. She was wondering if she should see a specialist.
11. When to Refer Patients to a Specialist Referral to specialists depends on oncologists' comfort level, but patients who have not responded to non-pharmacologic interventions with persistent insomnia on multiple sleep medications should be referred to a sleep specialist. It is important to involve the patients' primary care physicians in the management of insomnia. If the patients are interested in CBT programs, they should be referred to see a psychologists or behavioral sleep medicine specialists. If there is a high suspicion for OSA or other primary sleep disorders, referral to sleep medicine specialists or pulmonologists should also be considered.
12. Case Study Continued Mrs. H was admitted three months later due to pneumonia. Her family was concerned that she was not sleeping in the hospital and was progressively getting more confused. Her primary team prescribed melatonin 3 mg to help with her insomnia, and also instituted a
number of non-pharmacologic orders (Table 3). The following day, she was sleeping better.
13. Inpatient Management of Insomnia Older patients with cancer undergoing treatments are more likely to experience complications and adverse events from their cancer and cancer treatment, often requiring hospitalizations.51 Managing older adults with cancer in the hospital is complex due to frequent co-existing comorbidities and polypharmacy, requiring recurring visits from various healthcare professionals with frequent interruptions, which can often precipitate insomnia. Their increased sensitivity to environmental changes can also exacerbate their insomnia (such as increased anxiety with unfamiliar environment). Although the management of insomnia in the inpatient is similar to the outpatient setting, a number of inpatient-specific non-pharmacologic interventions can be instituted, as shown in Table 3.
14. Conclusion Older adults with cancer are at risk for insomnia. Insomnia can impact quality of life and lead to daytime fatigue. Many pharmaceuticals approved for insomnia are high-risk choices for older adults. Non-pharmacological methods of promoting sleep are effective in managing insomnia and should be used first line in older adults. An organized teaching plan with patient instructions can assist in minimizing or eliminating the use of drugs for sleep promotion and improve patient satisfaction with sleep quality.
Fig. 1 – Algorithm in the management of insomnia in older adults with cancer. The algorithm is developed by a multidisciplinary team consisting of healthcare professionals in medical oncology, palliative care, psychiatry, psychology, pharmacy, and nursing at the City of Hope Comprehensive Cancer Center. The multidisciplinary team reviewed and synthesized relevant literature (27 key journal articles and American Geriatric Society [AGS] guidelines) to identify evidence-based interventions for insomnia. Based on this review the expert panel worked to develop a consensus and recommendations for non-pharmacological as well as pharmacological options for insomnia, including special considerations for older adults. OSA: Obstructive sleep apnea; COPD: Chronic obstructive pulmonary disease; CHF: Congestive heart failure; GERD: Gastroesophageal reflux disorder; ESS: Epworth Sleepiness Scale; PSQI: Pittsburgh Sleep Quality Index; ISI: Insomnia Severity Scale. (See Tables 3 and 4.) Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003
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Disclosures and Conflict of Interest Statements The authors have no conflict of interest to report.
Author Contributions Quality control of data and algorithms: KP Loh, P Burhenn. Manuscript preparation: KP Loh, P Burhenn. Manuscript editing: A Hurria, F Zachariah, SG Mohile. Manuscript review: KP Loh, P Burhenn, A Hurria, F Zachariah, SG Mohile.
Acknowledgement We would like to acknowledge the following members on the multidisciplinary team who were involved in developing the algorithm: Peggy Burhenn, MS, CNS, AOCNS; Arti Hurria, MD; Finly Zachariah, MD; Sorin Buga, MD; Stephanie Davidson, PsyD; Carl Kildoo, PharmD; Yvette McLin, MD; Sepideh Shayani, PharmD and Carin van Zyl, MD.
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Please cite this article as: Loh KP, et al, How do I best manage insomnia and other sleep disorders in older adults with cancer?, J Geriatr Oncol (2016), http://dx.doi.org/10.1016/j.jgo.2016.05.003