Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments.

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Sleep disturbances include insomnia (trouble falling or staying asleep resulting in daytime dysfunction), excessive sleepiness (which can result from insufficient sleep opportunity, insomnia, or other sleep disorders), sleep-related movement or breathing disorders, and parasomnias.1 Sleep disorders affect 30% to 50% of patients with cancer and survivors, often in combination with fatigue, anxiety, or depression.1-10 Improvements in sleep lead to improvements in fatigue, mood, and quality of life.11 Most clinicians, however, do not know how best to evaluate and treat sleep disorders.1

Sleep disorders are common in patients with cancer as a result of multiple factors, including biologic changes, the stress of diagnosis and treatment, and side effects of therapy (eg, pain, fatigue).12 In addition, evidence suggests that changes in inflammatory processes from cancer and its treatment play a role in sleep disorders. These sleep disturbances can be perpetuated in the survivorship phase by chronic side effects, anxiety, depression, medications, and maladaptive behaviors such as shifting sleep times, excessive time in bed because of fatigue, and unplanned naps.12

Additional information about sleep disorders in patients with cancer can be found in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Palliative Care and the NCCN Guidelines for Cancer-Related Fatigue (available at NCCN.org). These guidelines may be modified to fit the individual survivor’s circumstances.

Screening for and Assessment of Sleep Disorders

Survivors should be screened for possible sleep disorders at regular intervals, especially when they experience a change in clinical status or treatment. The panel lists screening questions that can help determine whether concerns about sleep disorders or disturbances warrant further assessment. Other tools to screen for sleep problems have been validated.13,14

F1NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 12, 5; 10.6004/jnccn.2014.0067

F2NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 12, 5; 10.6004/jnccn.2014.0067

F3NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 12, 5; 10.6004/jnccn.2014.0067

F4NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 12, 5; 10.6004/jnccn.2014.0067

If concerns regarding sleep are significant, the panel recommends that treatable contributing factors be assessed and managed. Comorbidities that can contribute to sleep problems include alcohol and substance abuse, obesity, cardiac dysfunction, endocrine dysfunction, anemia, neurologic disorders, pain, fatigue, and emotional distress. In addition, some medications, both prescription and over-the-counter, can contribute to sleep issues. For instance, pain medication, antiemetics, and antihistamines can all contribute to sleep disturbance, as can the persistent use of sleep aids.

Diagnosis of Sleep Disorders

The panel divided sleep disorders into 2 general categories: insomnia, and sleep disturbance and/or excessive sleepiness.

Insomnia is diagnosed when patients have difficulty falling asleep and/or maintaining sleep at least 3 times per week for at least 4 weeks, accompanied by distress.

Diagnosing patients with excessive sleepiness can be challenging, because it can be caused by a variety of factors. When excessive sleepiness is associated with observed apneas or snoring, the STOP questionnaire can be used as a screening tool to determine the risk of obstructive sleep apnea (OSA).15 Other screening tools for OSA risk have also been validated.16 Sleep studies (ie, laboratory polysomnography [PSG] or home sleep studies) can confirm the diagnosis of OSA. Multiple sleep latency tests (MSLTs) and PSG can also be useful in diagnosing narcolepsy, idiopathic hypersomnia, and parasomnias. Narcolepsy should be considered when excessive sleepiness is accompanied by cataplexy, frequent short naps, vivid dreams, disrupted sleep, or sleep paralysis.

Excessive sleepiness can also be associated with uncomfortable sensations or an urge to move the legs (and sometimes the arms or other body parts). These symptoms are usually worse at night and with inactivity, may be improved or relieved with movement such as walking or stretching, and indicate restless legs syndrome (RLS; also known as Willis-Ekbom disease). In these patients, ferritin levels should be checked; levels less than 45 to 50 ng/mL indicate a treatable cause of RLS.17,18

Management of Sleep Disorders

OSA should be treated with continuous positive airway pressure, surgery, or oral appliances.19-21 Additionally, weight loss and exercise should be recommended, and patients should be referred to a sleep specialist.

RLS is treated with dopamine agonists, benzodiazepines, gabapentin, and/or opioids, and referral to a sleep specialist.22-30 Two separate recent meta-analyses found dopamine agonists and calcium channel alpha-2-delta ligands (eg, gabapentin) to be helpful in reducing RLS symptoms and improving sleep in the noncancer setting.30,31

For other types of sleep disturbances, several types of interventions are recommended.1,32,33 In addition, referral to a sleep specialist can be considered in most cases.

Sleep Hygiene Education

Educating survivors about general sleep hygiene is recommended, especially for the treatment of insomnia.34-36 Key points are listed in the guidelines and include regular morning or afternoon exercise; day-time exposure to bright light; keeping the sleep environment dark, quiet, and comfortable; and avoiding heavy meals, alcohol, and nicotine near bedtime.

Physical Activity

Physical activity may improve sleep in patients with cancer and survivors.37-43 One recent randomized controlled trial compared a standardized yoga intervention plus standard care with standard care alone in 410 survivors (75% breast cancer; 96% women) with moderate to severe sleep disruption.40 Participants in the yoga arm experienced greater improvements in global and subjective sleep quality, daytime functioning, and sleep efficiency (all P≤.05). In addition, the use of sleep medication declined in the intervention arm (P≤.05).

A recent meta-analysis of randomized controlled trials in patients who had completed active cancer treatment showed that exercise improved sleep at a 12-week follow-up.38 Overall, however, data supporting improvement in sleep with physical activity are limited in the survivorship population.

Psychosocial Interventions

Psychosocial interventions such as cognitive behavioral therapy (CBT), psychoeducational therapy, and supportive expressive therapy are recommended to treat sleep disturbances in cancer survivors.44 In particular, several randomized controlled trials have shown that CBT improves sleep in the survivor population.45-48 For example, a randomized controlled trial in 150 survivors (58% breast cancer; 23% prostate cancer; 16% bowel cancer; 69% women) found that a series of 5 weekly group CBT sessions was associated with a reduction in mean wakefulness of almost 1 hour per night, whereas usual care (in which physicians could treat insomnia as they would in normal clinical practice) had no effect on wakefulness.45

In addition, a small randomized controlled trial of 57 survivors (54% breast cancer; 75% women) found that mind-body interventions (mindfulness meditation or mind-body bridging), decreased sleep disturbance more than sleep hygiene education did.49

Pharmacologic Interventions

Many pharmacologic treatments for sleep disturbances are available, including psychostimulants for narcolepsy (eg, modafinil, methylphenidate) and hypnotics for insomnia (eg, zolpidem, ramelteon).33,50,51 In addition, antidepressants, antihistamines, antiepileptics, and antipsychotics are often used off-label for the treatment of insomnia, even though limited to no efficacy or effectiveness data are available for this use. The panel also noted that these medications are associated with significant risks and should be used with caution. One small, open-label study found that the antidepressant mirtazapine increased the total amount of nighttime sleep in patients with cancer.52 Overall, however, data on pharmacologic interventions aimed at improving sleep in patients with cancer and survivors are lacking.10

Individual Disclosures for the NCCN Sleep Disorders Panel

T1

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    NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

    Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery
    NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

    Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery
    NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

    Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • View in gallery
    NCCN Clinical Practice Guidelines in Oncology: Survivorship: Sleep Disorders, Version 1.2014

    Version 1.2014, 03-07-14 ©2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

  • 1.

    Berger AM, Mitchell SA. Modifying cancer-related fatigue by optimizing sleep quality. J Natl Compr Canc Netw 2008;6:313.

  • 2.

    Ancoli-Israel S, Moore PJ, Jones V. The relationship between fatigue and sleep in cancer patients: a review. Eur J Cancer Care (Engl) 2001;10:245255.

    • Search Google Scholar
    • Export Citation
  • 3.

    Ancoli-Israel S. Recognition and treatment of sleep disturbances in cancer. J Clin Oncol 2009;27:58645866.

  • 4.

    Carney S, Koetters T, Cho M. Differences in sleep disturbance parameters between oncology outpatients and their family caregivers. J Clin Oncol 2011;29:10011006.

    • Search Google Scholar
    • Export Citation
  • 5.

    Fiorentino L, Ancoli-Israel S. Insomnia and its treatment in women with breast cancer. Sleep Med Rev 2006;10:419429.

  • 6.

    Fiorentino L, Ancoli-Israel S. Sleep dysfunction in patients with cancer. Curr Treat Options Neurol 2007;9:337346.

  • 7.

    Flynn KE, Shelby RA, Mitchell SA. Sleep-wake functioning along the cancer continuum: focus group results from the Patient-Reported Outcomes Measurement Information System (PROMIS®). Psychooncology 2010;19:10861093.

    • Search Google Scholar
    • Export Citation
  • 8.

    Forsythe LP, Helzlsouer KJ, MacDonald R, Gallicchio L. Daytime sleepiness and sleep duration in long-term cancer survivors and non-cancer controls: results from a registry-based survey study. Support Care Cancer 2012;20:24252432.

    • Search Google Scholar
    • Export Citation
  • 9.

    Liu L, Ancoli-Israel S. Sleep disturbances in cancer. Psychiatr Ann 2008;38:627634.

  • 10.

    Zee PC, Ancoli-Israel S. Does effective management of sleep disorders reduce cancer-related fatigue? Drugs 2009;69 (Suppl 2):2941.

  • 11.

    Dirksen SR, Epstein DR. Efficacy of an insomnia intervention on fatigue, mood and quality of life in breast cancer survivors. J Adv Nurs 2008;61:664675.

    • Search Google Scholar
    • Export Citation
  • 12.

    Palesh O, Aldridge-Gerry A, Ulusakarya A. Sleep disruption in breast cancer patients and survivors. J Natl Compr Canc Netw 2013;11:15231530.

    • Search Google Scholar
    • Export Citation
  • 13.

    Omachi TA. Measures of sleep in rheumatologic diseases: Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire (FOSQ), Insomnia Severity Index (ISI), and Pittsburgh Sleep Quality Index (PSQI). Arthritis Care Res (Hoboken) 2011;63(Suppl 11):S287296.

    • Search Google Scholar
    • Export Citation
  • 14.

    Savard MH, Savard J, Simard S, Ivers H. Empirical validation of the Insomnia Severity Index in cancer patients. Psychooncology 2005;14:429441.

  • 15.

    Chung F, Yegneswaran B, Liao P. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008;108:812821.

  • 16.

    Silva GE, Vana KD, Goodwin JL. Identification of patients with sleep disordered breathing: comparing the four-variable screening tool, STOP, STOP-Bang, and Epworth Sleepiness Scales. J Clin Sleep Med 2011;7:467472.

    • Search Google Scholar
    • Export Citation
  • 17.

    Buchfuhrer MJ. Strategies for the treatment of restless legs syndrome. Neurotherapeutics 2012;9:776790.

  • 18.

    Moyer DE, Zayas-Bazan J, Reese G. Restless legs syndrome: diagnostic time-savers, Tx tips. J Fam Pract 2009;58:415423.

  • 19.

    Antonescu-Turcu A, Parthasarathy S. CPAP and bi-level PAP therapy: new and established roles. Respir Care 2010;55:12161229.

  • 20.

    Ballard RD. Management of patients with obstructive sleep apnea. J Fam Pract 2008;57:S2430.

  • 21.

    Weingarten JA, Basner RC. Advances in the management of adult obstructive sleep apnea. F1000 Med Rep 2009;1.

  • 22.

    Bassetti CL, Bornatico F, Fuhr P. Pramipexole versus dual release levodopa in restless legs syndrome: a double blind, randomised, cross-over trial. Swiss Med Wkly 2011;141:w13274.

    • Search Google Scholar
    • Export Citation
  • 23.

    Ferini-Strambi L, Aarskog D, Partinen M. Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial. Sleep Med 2008;9:874881.

    • Search Google Scholar
    • Export Citation
  • 24.

    Kaplan PW, Allen RP, Buchholz DW, Walters JK. A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene. Sleep 1993;16:717723.

    • Search Google Scholar
    • Export Citation
  • 25.

    Manconi M, Ferri R, Zucconi M. Pramipexole versus ropinirole: polysomnographic acute effects in restless legs syndrome. Mov Disord 2011;26:892895.

    • Search Google Scholar
    • Export Citation
  • 26.

    Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology 1999;52:938943.

    • Search Google Scholar
    • Export Citation
  • 27.

    Oertel WH, Stiasny-Kolster K, Bergtholdt B. Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study). Mov Disord 2007;22:213219.

    • Search Google Scholar
    • Export Citation
  • 28.

    Trenkwalder C, Garcia-Borreguero D, Montagna P. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004;75:9297.

    • Search Google Scholar
    • Export Citation
  • 29.

    Walters AS, Ondo WG, Dreykluft T. Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebocontrolled study. Mov Disord 2004;19:14141423.

    • Search Google Scholar
    • Export Citation
  • 30.

    Wilt TJ, MacDonald R, Ouellette J. Pharmacologic therapy for primary restless legs syndrome: a systematic review and meta-analysis. JAMA Intern Med 2013;173:496505.

    • Search Google Scholar
    • Export Citation
  • 31.

    Hornyak M, Scholz H, Kohnen R. What treatment works best for restless legs syndrome? Meta-analyses of dopaminergic and non-dopaminergic medications. Sleep Med Rev 2013.

    • Search Google Scholar
    • Export Citation
  • 32.

    Morgenthaler T, Kramer M, Alessi C. Practice parameters for the psychological and behavioral treatment of insomnia: an update. An American Academy of Sleep Medicine report. Sleep 2006;29:14151419.

    • Search Google Scholar
    • Export Citation
  • 33.

    Morgenthaler TI, Kapur VK, Brown T. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep 2007;30:17051711.

    • Search Google Scholar
    • Export Citation
  • 34.

    Insomnia: assessment and management in primary care. National Heart, Lung, and Blood Institute Working Group on Insomnia. Am Fam Physician 1999;59:30293038.

    • Search Google Scholar
    • Export Citation
  • 35.

    Kupfer DJ, Reynolds CF 3rd. Management of insomnia. N Engl J Med 1997;336:341346.

  • 36.

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