Survivorship: Sleep Disorders, Version 1.2014

Abstract

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.

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

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; daytime 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

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.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines^® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network^® (NCCN^®) makes no representation or warranties of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way. The full NCCN Guidelines for Survivorship are not printed in this issue of JNCCN but can be accessed online at NCCN.org.

© National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.

NCCN Sleep Disorders Panel Members

^*,a,cCrystal S. Denlinger, MD/Chair†, Fox Chase Cancer Center

^*,c,dJennifer A. Ligibel, MD/Vice Chair†, Dana-Farber/Brigham and Women’s Cancer Center

^fMadhuri Are, MD£, Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center

^b,eK. Scott Baker, MD, MS€ξ, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance

^cWendy Demark-Wahnefried, PhD, RD≅, University of Alabama at Birmingham, Comprehensive Cancer Center

^b,dDebra L. Friedman, MD, MS€‡, Vanderbilt-Ingram Cancer Center

^*,gMindy Goldman, MDΩ, UCSF Helen Diller Family Comprehensive Cancer Center

^c,dLee Jones, PhDΠ, Memorial Sloan-Kettering Cancer Center

^bAllison King, MD€Ψ‡, Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Grace H. Ku, MDξ‡, UC San Diego Moores Cancer Center

^b,hElizabeth Kvale, MD£, University of Alabama at Birmingham, Comprehensive Cancer Center

^aTerry S. Langbaum, MAS¥, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

^gKristin Leonardi-Warren, RN, ND#, University of Colorado Cancer Center

^bMary S. McCabe, RN, BS, MS#, Memorial Sloan-Kettering Cancer Center

^b,c,d,gMichelle Melisko, MD†, UCSF Helen Diller Family Comprehensive Cancer Center

^eJose G. Montoya, MDΦ, Stanford Cancer Institute

^a,dKathi Mooney, RN, PhD#, Huntsman Cancer Institute at the University of Utah

^c,eMary Ann Morgan, PhD, FNP-BC#, Moffitt Cancer Center

Javid J. Moslehi, MDλÞ, Dana-Farber/Brigham and Women’s Cancer Center

^d,hTracey O’Connor, MD†, Roswell Park Cancer Institute

^cLinda Overholser, MD, MPHÞ, University of Colorado Cancer Center

^cElectra D. Paskett, PhDε, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

^f,hMuhammad Raza, MD‡, St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center

^fKaren L. Syrjala, PhDθ, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance

^*,fSusan G. Urba, MD†£, University of Michigan Comprehensive Cancer Center

^gMark T. Wakabayashi, MD, MPHΩ, City of Hope Comprehensive Cancer Center

^*,hPhyllis Zee, MDΨΠ, Robert H. Lurie Comprehensive Cancer Center of Northwestern University

NCCN Staff: Nicole McMillian, MS, and Deborah Freedman-Cass, PhD

KEY:

*Writing Committee Member

Subcommittees: ^aAnxiety and Depression; ^bCognitive Function; ^cExercise; ^dFatigue; ^eImmunizations and Infections; ^fPain; ^gSexual Function; ^hSleep Disorders

Specialties: ξBone Marrow Transplantation; λCardiology; εEpidemiology; ΠExercise/Physiology; ΩGynecology/Gynecologic Oncology; ‡Hematology/Hematology Oncology; ΦInfectious Diseases; ÞInternal Medicine; †Medical Oncology; ΨNeurology/Neuro-Oncology; #Nursing; ; ≅Nutrition Science/Dietician; ¥Patient Advocacy; €Pediatric Oncology; θPsychiatry, Psychology, Including Health Behavior; £Supportive Care Including Palliative, Pain Management, Pastoral Care, and Oncology Social Work; ¶Surgery/Surgical Oncology; ωUrology