Journal of Pain and Symptom Management
Volume 39, Issue 1 , Pages 126-138, January 2010

Mind-Body Treatments for the Pain-Fatigue-Sleep Disturbance Symptom Cluster in Persons with Cancer

School of Nursing, University of Wisconsin-Madison, Madison, Wisconsin, USA

Accepted 17 June 2009. published online 09 November 2009.

Article Outline

Abstract 

Context

Co-occurring pain, fatigue, and sleep disturbance comprise a common symptom cluster in patients with cancer. Treatment approaches that target the cluster of symptoms rather than just a single symptom need to be identified and tested.

Objectives

To synthesize evidence regarding mind-body interventions that have shown efficacy in treating two or more symptoms in the pain-fatigue-sleep disturbance cancer symptom cluster.

Methods

A literature search was conducted using CINAHL, Medline, and PsychInfo databases through March 2009. Studies were categorized based on the type of mind-body intervention (relaxation, imagery/hypnosis, cognitive-behavioral therapy/coping skills training [CBT/CST], meditation, music, and virtual reality), and a preliminary review was conducted with respect to efficacy for pain, fatigue, and sleep disturbance. Mind-body interventions were selected for review if there was evidence of efficacy for at least two of the three symptoms. Forty-three studies addressing five types of mind-body interventions met criteria and are summarized in this review.

Results

Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance. Relaxation has resulted in improvements in pain and sleep disturbance. Meditation interventions have demonstrated beneficial effects on fatigue and sleep disturbance. Music interventions have demonstrated efficacy for pain and fatigue. No trials were found that tested the mind-body interventions specifically for the pain-fatigue-sleep disturbance symptom cluster.

Conclusion

Efficacy studies are needed to test the impact of relaxation, imagery/hypnosis, CBT/CST, meditation, and music interventions in persons with cancer experiencing concurrent pain, fatigue, and sleep disturbance. These mind-body interventions could help patients manage all the symptoms in the cluster with a single treatment strategy.

Key Words: Pain, fatigue, sleep disturbance, cancer, mind-body and relaxation techniques

 

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Introduction 

Persons with cancer experience a range of symptoms related to both the disease and its treatment. Recent evidence has demonstrated that certain symptoms tend to co-occur or “cluster” together, exacerbating the overall symptom experience.1, 2 In some cases, there may be shared mechanisms causing each of the symptoms to occur (e.g., cytokine-induced nausea and vomiting). In other cases, having one symptom may cause or exacerbate another (e.g., uncontrolled pain may interrupt one's sleep). Finally, treatment strategies used for a particular symptom may produce side effects that manifest as new symptoms (e.g., using opioids to control pain may leave one feeling fatigued). Most studies have focused on identifying treatments for individual symptoms, but given new awareness of symptom clusters, it now appears that this piecemeal approach may be flawed. Treatment approaches may have greater effects if they target a cluster of symptoms rather than one single symptom. This article will review evidence for mind-body interventions to identify those that may be efficacious in treating the symptom cluster of co-occurring pain, fatigue, and sleep disturbance in cancer.

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Background 

The focus of cancer symptom management research has recently shifted as investigators acknowledge that symptoms typically do not occur in isolation. Symptom clusters are defined as combinations of two or more co-occurring symptoms that are related to each other and that are independent of other symptoms or symptom clusters.3, 4 Symptoms within the cluster may share the same etiology, but are not required to do so. Some of the symptoms may be related to the cancer itself, whereas others are brought about by cancer treatment strategies. When occurring together, the symptoms may have a greater impact on physical function, emotional distress, and overall quality of life than was previously attributed to symptoms occurring in isolation.

Barsevick5 used the term “crossover” in suggesting that treatments shown to benefit a single symptom may have a broad spectrum of effect and could also impact other symptoms in the cluster. Williams6 hypothesized that a single intervention may impact the entire symptom cluster, noting that: (1) the symptoms may share a common etiology, (2) diminishing one symptom may prevent exacerbations in others, and (3) single interventions may be indicated for more than one symptom. She also noted possible benefits of using a single intervention in that it simplifies treatment, reduces the risk for side effects, and may reduce costs. In this article, the term “crossover” is used to describe treatments that have demonstrated efficacy for more than one of the cluster component symptoms and may, therefore, be beneficial in treating the symptom cluster as a whole. It is our position that such crossover treatments should be given priority in symptom cluster management trials.

The most well-documented and studied symptom cluster is the combination of pain, fatigue, and sleep disturbance. Pain, fatigue, and sleep disturbance are among the most common symptoms experienced by persons with cancer.7 Pain is reported by 59% of persons receiving anticancer treatment and 64% of those with advanced, metastatic, or terminal disease.8 Fatigue, the most common symptom experienced by all the persons with cancer, impacts more than 75% of patients.9, 10, 11 Sleep problems, such as difficulty falling asleep, frequent nighttime wakening, waking too early in the morning, or excessive daytime sleeping, are reported by up to 72% of persons with cancer.12, 13 These three symptoms have been found to cluster, co-occurring in more than 40% of patients, particularly those receiving cancer treatment.14, 15, 16, 17 Moderate positive correlations between the three symptoms have been documented in persons with various cancer diagnoses and stages of disease.14 If not adequately managed, the symptoms in this cluster may interfere with mood, role and social functions, ability to tolerate and continue cancer therapies, and overall quality of life.18, 19, 20, 21, 22, 23

Traditional medical management of pain, fatigue, or sleep disturbance has focused on the use of pharmaceutical treatments such as analgesics, psychostimulants, hematopoietic growth factors, or sedatives. Specific medications prescribed for one symptom, however, may unintentionally worsen the other symptoms. For example, opioid pain medications may cause feelings of tiredness and increase daytime napping, which, in turn, leads to less restful nighttime sleep. Disruptions in sleep may exacerbate daytime fatigue, causing increased sensitivity to pain. Sleep disturbance related to steroid use may result in inadequate rest and intensify fatigue. On the other hand, use of sedatives or sleep enhancers may result in sensations of grogginess or lack of alertness throughout the day, which could intensify fatigue and contribute to muscle aches and pain. It appears that the pain-fatigue-sleep disturbance symptom cluster cannot be optimally managed with the use of medications alone. Nonpharmacologic, mind-body interventions may provide a beneficial addition to the treatment regimen.

Mind-body interventions are techniques that “focus on the interactions among the brain, mind, body, and behavior, and on the…ways in which emotional, mental, social, spiritual, and behavioral factors can directly affect health.”24 Examples of mind-body interventions include relaxation, hypnosis, imagery, meditation, and cognitive or behavioral techniques, among others. The goal of mind-body interventions is to provide patients with the knowledge and skills to cope with and achieve personal control over their symptoms. Mind-body interventions are particularly appealing options to explore for the treatment of cancer symptom clusters as they are inexpensive, can be used in addition to pharmacologic strategies, have relatively few negative side effects, and can be implemented by patients independently with sufficient training.

Pain, fatigue, and sleep disturbance share a psychological component. Factors such as anxiety and meaning of the cancer symptoms may intensify how the symptoms are perceived and experienced.25 The Theory of Unpleasant Symptoms suggests that psychosocial factors such as mental state, reaction to illness, and anxiety are antecedents to symptoms that help define the overall symptom experience.26, 27 Depression is often noted as being related to pain, fatigue, and sleep disturbance in cancer, and some investigators have included depression as a component of the symptom cluster itself.17 Interventions to enhance coping, diminish stress and anxiety, and improve mood may, therefore, help to improve the pain-fatigue-sleep disturbance symptom cluster.28 Mind-body interventions may be useful in altering negative thoughts about cancer, the underlying cause of symptoms, or in reframing how the symptoms are interpreted. The interventions may improve mood and provide a more optimistic attitude toward one's ability to cope with pain, fatigue, and sleep disturbance. Mind-body interventions may also enhance relaxation and reduce stress and anxiety related to the symptom experience. The physical and mental effects of relaxation may reduce sensitivity to pain sensations, allow more restful sleep, and reduce fatigue.

The purpose of this literature review was to identify mind-body interventions for which evidence suggests beneficial effects on at least two of the three cluster component symptoms (pain, fatigue, and sleep disturbance), and to synthesize that evidence. These interventions may hold potential for use as treatment for the full symptom cluster.

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Methods 

CINAHL, Medline, and PsycINFO databases were searched through March 2009 using selected terms for mind-body interventions (guided imagery, hypnosis, relaxation, biofeedback, cognitive-behavioral therapy, coping skills training, meditation, virtual reality, and music) combined with the term cancer and terms for any of the three symptoms of interest (pain, fatigue, sleep disturbance, sleep difficulty, insomnia). We restricted our search to those mind-body interventions that involve primarily mental activity, as they can be performed by nearly all the patients, including those with advanced disease. Although yoga is classified as a mind-body intervention by the National Center for Complementary and Alternative Medicine,24 there is disagreement in the literature, with some investigators describing the intervention as physical exercise involving “vigorous…aerobic activity” (p. 127).29 Thus, we did not include “yoga” in our search. Results were limited to English language, research, and adults (age≥18 years).

Abstracts were reviewed and articles were selected for inclusion if they tested one of the mind-body interventions in a sample of patients with cancer and if pain, fatigue, or sleep disturbance was among the dependent variables. We eliminated studies in which patients were undergoing diagnostic testing for cancer (i.e., a cancer diagnosis had not yet been established), as well as studies that included both persons with and without cancer in their samples.

Next, we placed studies into one of six categories by intervention type: 1) relaxation, 2) imagery/hypnosis, 3) cognitive-behavioral therapy/coping skills training [CBT/CST], 4) meditation, 5) music, and 6) virtual reality. We categorized studies based on the description of the intervention provided in the research report. If the study included more than one intervention, it was categorized based on the most complex intervention included in the study. For example, if a CBT intervention was compared to a simple relaxation intervention, the study was categorized as a test of the more complex intervention, CBT. Descriptions of each type of intervention are provided in the Results section.

We conducted a preliminary review and identified those mind-body interventions for which beneficial effects were demonstrated on at least two of the three symptoms. Studies of those interventions were then reviewed in detail using a systematic narrative approach. We did not compute study quality scores, as our intent was to cast a broad net for those mind-body interventions that currently hold promise as treatment for the symptom cluster. Those interventions can then be targeted for immediate study.

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Results 

Evidence for Crossover Mind-Body Interventions 

A total of 47 published articles were identified that tested a mind-body strategy for pain, fatigue, and/or sleep disturbance in persons with cancer. Of the six types of mind-body interventions searched, all but virtual reality had studies supporting beneficial effects on at least two of the three symptoms of interest (Table 1). The four studies that tested a virtual reality intervention provided evidence for effects on fatigue only, and are not addressed in this review. The 43 studies of 1) relaxation 2) imagery/hypnosis, 3) CBT/CST, 4) meditation, and 5) music are described and their findings synthesized in the following pages.

Table 1. Evidence Supporting Effects of Mind-Body Interventions on Pain, Fatigue, and Sleep Disturbance
Mind-Body InterventionPainFatigueSleep Disturbance
CBT/coping skills trainingXXX
Guided imagery or hypnosisX X
Meditation XX
MusicXX
RelaxationX X
Virtual reality X

X=Evidence of beneficial effects on the symptom.

Relaxation 

Studies were categorized as “relaxation” if they tested a technique designed to elicit a state of relative freedom from mental and/or physical tension.30 The use of relaxation as a therapeutic intervention dates back many decades. In the early 1900s, Jacobsen developed the progressive muscle relaxation (PMR) technique to stimulate physical and mental relaxation by focusing attention on the sensations associated with systematically tensing and relaxing groups of muscles.31 A variety of other relaxation exercises have been developed, such as jaw relaxation (relaxing muscles of the face, mouth, and jaw), focused breathing (focusing attention on a relaxing word or phrase and slow, regular respirations), or abdominal breathing (slow deep breathing using muscles of the abdomen). Relaxation exercises minimize sympathetic nervous system response, which decreases oxygen demand, slows heart rate and respirations, and lowers blood pressure.32 Relaxation interventions may improve symptoms by eliminating physical tension and emotional stressors, and by facilitating the ability to become comfortable, rest, and fall asleep.25

Relaxation interventions were implemented as the experimental treatment in six studies (Supplementary Table 2). Pain was the most frequently studied outcome. It was the primary focus of four efficacy trials, with beneficial effects demonstrated in three. Samples included hospitalized patients with cancer pain, outpatients with chronic cancer pain, and women with early stage breast cancer. Significantly greater pain relief was obtained with PMR when compared to massage, treatment as usual,33 positive mood manipulation, distraction, and a no-treatment control condition.34 Biofeedback-assisted relaxation resulted in greater pain relief when compared to attention control (e.g., time spent with a nurse).35 Domar et al.,36 however, found no significant differences in pain between a daily relaxation exercise and a distraction condition among patients having surgical skin cancer resection.

One study each explored the effect of relaxation training on fatigue and sleep disturbance. Training in PMR did not improve fatigue in patients receiving radiotherapy when compared to an informational intervention,37 but PMR training did improve sleep in patients with insomnia when compared to treatment as usual.38

Two additional studies used relaxation interventions as comparison conditions in studies of imagery interventions. Both compared PMR to standard care in hospitalized patients. One demonstrated a significant reduction in pain with PMR,39 but the other found no differences in pain or fatigue.40

Imagery/Hypnosis 

Studies were categorized as “imagery/hypnosis” if they tested an intervention that asked participants to create specific mental images with the intent of bringing about positive physical or emotional effects.41 Despite their different names, imagery and hypnosis have been noted to be quite similar in terms of practice. Both interventions focus on the creation of mental representations, through recall of memories or creative imagination that change the desired outcome (e.g., symptom experience).42 Pleasant images may be created to distract attention away from the noxious symptom. Alternatively, images of the unpleasant symptom may be modified to change the symptom experience.43 Investigators have suggested that the body mimics neurohormonal responses to the mental images, as if they were actually occurring.41, 44 The mental images may also alter expectations for outcome, such that the desired outcome occurs automatically in response to the new image.44

Imagery/hypnosis interventions served as the experimental intervention in six studies (Supplementary Table 3). Four studies tested imagery interventions in hospitalized patients with cancer pain, and all reported beneficial effects; one in a pretest-posttest design45 and three when compared to treatment-as-usual or attention control conditions.39, 46, 47 Conversely, Haase et al.40 found no significant differences in pain and no differences in fatigue between patients receiving an imagery intervention and those receiving standard care with colorectal surgery. Elkins et al.48 tested a hypnosis intervention among women with breast cancer who were experiencing hot flashes and reported a significant improvement in sleep scores in the hypnosis group compared to a no treatment control condition.

Four additional studies used imagery interventions as comparison conditions in studies of CBT/CST. All combined imagery with relaxation instructions. One study reported no change in pain or fatigue,49 but two reported significant reductions in pain50, 51 and one reported significant reductions in fatigue and sleep disturbance.52

Cognitive-Behavioral Therapy/Coping Skills Training 

Studies were categorized as “CBT/CST” if the intervention aimed to change patients' thoughts as a way to influence their feelings and behaviors, helping patients to recognize and subsequently control their response to symptoms using a programmed education or counseling approach. Interventions that combined training in more than two cognitive or behavioral coping strategies in a single treatment group were also included in this category as coping skills training. What an individual thinks and believes about his/her symptoms, including thoughts about the symptom's meaning, controllability, and consequences, influence how symptoms are experienced. In CBT/CST interventions, participants are taught to understand how their thoughts influence their feelings and behavior, to recognize and acknowledge when this is occurring, and to use cognitive strategies and coping skills to change their thoughts and behaviors. The interventions are usually delivered over several weeks and involve assignments to practice what has been learned outside of the training sessions. If the patient experiences difficulty with the skills, problem solving and additional training are carried out at the next treatment session. As applied to symptom management, CBT/CST interventions focus on helping participants to identify and change maladaptive cognitions about their symptoms and use various cognitive and behavioral coping strategies that change how the symptoms are perceived and experienced.53

A total of 21 studies (24 publications) tested a program of CBT/CST in persons with cancer-related pain, fatigue, or sleep disturbance (Supplementary Table 4). Four studies tested CBT/CST interventions for pain. Robb et al.54 demonstrated a significant reduction in pain intensity among adults with chronic cancer pain after participating in a six-month pain-focused CBT intervention. Syrjala et al.50, 51 conducted two trials of a CBT intervention, comparing the treatment to treatment as usual for mucositis pain experienced by persons having a bone marrow transplant to treat hematologic malignancies. In the first study, pain reported by the CBT group was no different from pain reported by the control group. In the second study, CBT resulted in significantly less pain than the control condition.51 Dalton55 tested a similar self-care program among adults with cancer-related pain, but found no differences in pain ratings when compared to control.

Cancer-related fatigue was the primary focus of three studies of CBT/CST interventions; all demonstrated beneficial effects. Samples included patients receiving chemotherapy, patients who had completed treatment, and patients with malignant melanoma. Significantly greater improvements in fatigue were achieved with a 6–12-week CBT/CST intervention when compared to treatment as usual,56 wait-list control,57, 58 and a no treatment control condition.59

Three studies tested the effects of CST in managing the combination of pain and fatigue. Samples included women with metastatic breast cancer experiencing pain,49 patients undergoing curative radiation therapy,60 and women undergoing bone marrow transplant for breast cancer.61 All the studies compared a one-session CST intervention to a treatment-as-usual control condition. No significant differences in pain or fatigue were noted between groups in any of these studies.

Seven studies evaluated the effects of CBT/CST interventions on the combination of fatigue and sleep disturbance. Six of these studies involved samples of women with breast cancer52, 62, 63, 64, 65, 66, 67, 68 and one study included patients with a variety of cancer diagnoses.69 Williams and Schreier62 found decreased incidence of fatigue and sleep disturbance using a 20-minute coping skills audio-recording before each chemotherapy cycle compared to treatment as usual. In one-group designs, both Quesnel et al.64 and Berger et al.67, 68 reported significant improvement in sleep with a four- to eight-week CBT intervention, but only Quesnel also reported improvement in fatigue. Espie et al.69 found greater improvements in sleep and less fatigue after a five-session nurse-led CBT intervention compared to treatment as usual. Savard et al.63 and Epstein and Dirksen reported greater improvement in sleep, but no change in fatigue when four to eight weeks of CBT was compared to treatment as usual or sleep education.65, 66 Cohen and Fried52 reported no improvement in either fatigue or sleep disturbance with a nine-week CBT intervention compared to standard treatment.

Finally, four studies measured the effect of CBT/CST interventions on all the three symptoms concurrently: pain, fatigue, and sleep disturbance. One study documented improvement in two of the three symptoms. Davidson et al.70 tested an eight-week sleep focused CBT program in persons with cancer-related insomnia using a one-group pretest-posttest design. Significant improvements were documented in both fatigue and sleep disturbance, but pain remained unchanged. Arving et al.71 and Dalton et al.72 both tested individually tailored CBT interventions. Arving et al. reported significantly less sleep disturbance but no differences in pain or fatigue among women starting treatment for breast cancer following a nurse-led CBT intervention compared to control. Dalton et al.72 reported significantly lower ratings of “worst” pain immediately after the tailored CBT program, and greater reductions in pain and fatigue six months after the intervention compared to treatment-as-usual control. There were no differences in sleep. Vilela et al.73 found no significant differences in pain, fatigue, or sleep disturbance in patients with head and neck cancer using a CST intervention compared to control.

Meditation 

Studies were categorized as “meditation” if they provided training in a self-directed mental exercise to intentionally and continually focus the mind on a single target perception. Meditative techniques grew largely out of Eastern religious practices such as Hindu, Buddhist, and Taoist meditation.74 Mindfulness-based stress reduction (MBSR), a meditative technique that has grown in popularity over the last decade, involves awareness of body sensations and focused breathing to calm the mind and give the individual a sense of nonjudgmental awareness of bodily experiences.75 Some MBSR techniques include training in meditative exercises such as gentle yoga poses to help bring about the meditative state.76 Symptoms such as pain, fatigue, and sleep disturbance may be modified through meditation by focusing attention away from the symptom experience, by focusing on strengths and positive thoughts, by eliminating the evaluation or judgment of sensations associated with the symptom.77, 78, 79

Although no studies tested the effects of meditation on cancer-related pain, four studies evaluated the impact of meditation interventions on fatigue and/or sleep disturbance (Supplementary Table 5). Three studies specifically identified the type of meditation as MBSR; one used similar techniques, but simply described the intervention as meditation. Only one study reported beneficial effects, and that study used a one-group pretest-posttest design. Carlson and Garland77 reported a significant improvement in both fatigue and sleep disturbance among outpatients with cancer who participated in an eight-week MBSR intervention. Kieviet-Stijnen et al.80 studied an eight-week MBSR intervention in patients with various cancer diagnoses and found no within-group improvement in fatigue. Moadel et al.81 studied a 12-week meditation intervention in a sample of women with breast cancer and found no significant differences in fatigue when compared to a wait-list control condition. Similarly, Shapiro et al.82 tested a six-week MBSR intervention among women with breast cancer and found no differences in sleep disturbance when compared to a choice of other self-directed stress management techniques.

Music 

Studies were categorized as tests of “music” interventions if they promoted health and well-being through listening to or participating in music in some way.83 Music therapists sometimes involve persons in exploring thoughts and beliefs through music or expressing emotions by creating music, singing, or dancing, but simple music listening can also be an efficacious strategy in managing symptoms. Music can stimulate both physiologic and emotional reactions based on its pitch, intensity, tone, and rhythms.84 Certain styles of music may trigger relaxation, whereas others enhance mood, and still others energize the mind and body. In general, music provides a source of distraction by holding one's attention on the specific musical qualities. Particularly engaging music may distract attention from pain, relaxing music may release muscle tension and reduce pain, or stimulate muscle relaxation to enhance sleep and rest.30, 85 Fast-paced, up-tempo, positive music may energize and elevate the mood of someone who is feeling fatigued.86, 87

Four studies evaluated the effects of music interventions on pain (Supplementary Table 6). Cholburi et al.88 and Zimmerman et al.89 both reported significant pre- to post-treatment reductions in pain using 30 minutes of preferred music among hospitalized patients with cancer pain. Beck90 and Kwekkeboom,91 however, found no differences in pain when music listening was compared to a control condition (white noise, book on tape, or resting quietly).

Two studies tested a music intervention on cancer-related fatigue. Ferrer92 compared live music to a no treatment control condition among cancer patients receiving chemotherapy and reported significantly less fatigue in the music group. Burns et al.93 compared music with standard care in a sample of hospitalized patients receiving intensive chemotherapy and found no significant difference in fatigue between groups.

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Discussion 

A total of six mind-body interventions that had been studied for cancer-related pain, fatigue, or sleep disturbance were initially identified in this review; all the interventions except virtual reality demonstrated beneficial effects on at least two of the symptoms and met criteria for review. Findings suggest there is at least some evidence to support the use of CBT/CST interventions and imagery/hypnosis interventions for all the three symptoms. Relaxation has demonstrated efficacy in managing pain and sleep disturbance. Meditation has been supported in the treatment of both fatigue and sleep disturbance. Music has been efficacious in managing both pain and fatigue. This evidence suggests there is value in exploring these five mind-body interventions as potential crossover treatments for the pain-fatigue-sleep disturbance symptom cluster in persons with cancer.

Of the 15 studies that measured multiple symptom outcomes, only six indicated improvement in more than one symptom from the single intervention being tested. In each of those cases, the two symptoms improved were fatigue and sleep disturbance. Three of six studies used pretest-posttest, within-group designs. These studies did not control for the possibility of improvement simply due to passage of time rather than effects of the mind-body intervention. None of the studies demonstrated concurrent improvement in pain and fatigue or pain and sleep disturbance, and none demonstrated improvement in all the three symptoms. It is important to note, however, that none of these studies specifically targeted a symptom cluster as their focus of treatment. They simply measured other concurrent symptoms in addition to the primary symptom of interest. Most importantly, none of the studies used inclusion criteria to select patients who were experiencing the pain-fatigue-sleep disturbance symptom cluster. Thus, baseline symptom status may not have been sufficient to demonstrate significant improvement across the symptom cluster.

Relaxation interventions demonstrated efficacy in four of six trials in which relaxation was the primary intervention, and one of the two trials that used relaxation as a comparison condition. The greatest evidence was for its effect on cancer-related pain. No studies supported effects on fatigue, but one study did suggest improvement in sleep disturbance. Both inpatients and outpatients were included in the studies as well as patients on and off therapy (surgery, chemotherapy, radiation). The most frequently studied intervention was PMR delivered over three or more training sessions, facilitated with an audiotape and independent patient practice. Control conditions were most often described as treatment as usual. When more active comparison conditions were used (i.e., education and counseling, distracting activity, imagery), effects of relaxation did not differ significantly from those of the comparison group.

Imagery/hypnosis interventions demonstrated efficacy in five of six studies in which it was the primary treatment being tested, and three of four studies in which it was used as an active comparison condition. The majority of studies demonstrated support in relieving pain. Two studies documented improvement in sleep and one study documented improvement in fatigue with an imagery intervention. Most of these studies used randomized or crossover designs with treatment-as-usual control conditions. The imagery/hypnosis studies were conducted primarily with hospitalized patients experiencing cancer-related pain. Interventions ranged from a one-time 12-minute exercise to sessions of 50 minutes or more plus daily practice over several weeks.

CBT/CST interventions were efficacious in 14 of 21 studies. Studies demonstrated improvement in all the three symptoms, but the most support was demonstrated for fatigue and sleep disturbance. Nearly half of the studies involved women with breast cancer either during or after completing treatment. All of the studies that used experience of the symptom(s) of interest as an inclusion criteria demonstrated improvement in that symptom. Again, treatment as usual was the most frequent control condition, although some used active comparison conditions. Two studies compared CBT/CST interventions to education and found greater effect of the CBT/CST intervention in comparison;65, 72 however, three studies that used imagery interventions as a comparison found similar or stronger effects in the imagery group.50, 51, 52

Meditation interventions demonstrated efficacy in only one of the four studies, and those findings were within group differences in fatigue and sleep disturbance; a control or comparison condition was not included.77 Populations studied included only outpatients, most with early stage breast cancer and posttreatment. The relatively healthy samples may have precluded the ability to demonstrate improvement in symptoms. Both meditation studies that used control conditions failed to demonstrate significant effects of the mind-body intervention, regardless of whether the control was a wait-list or an active comparison (patient-selected stress management techniques such as talking with a friend or exercising).

Music interventions demonstrated greater effects than control or comparison conditions in three of the six studies. Evidence was strongest for effects on pain. One study documented beneficial effects on fatigue. No studies evaluated the effect of music on sleep disturbance. Patients studied were both inpatients and outpatients, with most experiencing the symptom of interest as inclusion criteria for the study. The length of music interventions were typically brief, 30–45 minutes delivered either as a one-time intervention or twice a day over two to three days. Four trials used randomized controlled designs with treatment as usual or “rest” as control conditions. Two used an active comparison condition involving a distraction technique or white noise, which did not differ from the effects of music.

Few investigators used multisymptom inventories in their studies, which could have provided useful leads in understanding the effects of mind-body interventions on co-occurring symptoms. Given that symptom cluster research is still a relatively new field, an ideal measure of the pain-fatigue-sleep disturbance symptom cluster has not yet been identified. Several scales used in the current studies appeared to have been sensitive to effects of the mind-body interventions. Those scales that most frequently detected changes in pain were the visual analog scale and the 0–10 numeric rating scale. Instruments that most frequently detected changes in fatigue included the visual analog scale, the fatigue, and vigor subscales from the Profile of Mood States,94 and the Multidimensional Fatigue Inventory.95 Measures most frequently sensitive to the effects of mind-body interventions on sleep disturbance included sleep diaries, the Pittsburgh Sleep Quality Index,96 sleep subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire,97 and the Insomnia Severity Index.98 Additional research is necessary to identify the items and scales most useful in measuring symptom clusters. The optimal measure would be sensitive to clinically relevant changes in each symptom, but also brief and simple to complete given the symptom burden experienced by the cancer population.

The studies we reviewed have several strengths. Nearly all were randomized controlled trials, offering the highest level of evidence for the interventions tested. The specific content of interventions was fairly consistent within each category. Although breast cancer was a common study population, a wide variety of patients were studied, including inpatients and outpatients, persons receiving treatment and those who had completed it, as well as persons with various diagnoses and stages of disease. Some of the studies required the presence of symptoms as an inclusion criterion, reducing the possibility of floor effects in these trials.

The studies did, however, have some limitations. Sample sizes used in most trials were small to moderate (n<100 in 35 of 43 trials). Specific doses (timing, frequency of practice) of CBT/CST interventions varied across studies. Relatively few studies tested meditation interventions. Most music interventions were fairly brief (one to six sessions delivered over <3 days) and few active comparison conditions were used in these studies. Several studies combined interventions and did not attempt to determine which intervention component actually produced the symptom improvement. Furthermore, most of the studies were efficacy trials, testing the mind-body interventions in a controlled, somewhat artificial context with a selected patient population. A few of the investigators described their studies as effectiveness trials, using clinic nurses69 or social workers61 to administer treatment in the clinical setting. As efficacy trials provide support for mind-body interventions in the context of treating a specific symptom cluster, effectiveness trials will need to be carried out to determine if the outcomes are reproducible in contemporary cancer care settings.

Limitations of this review must also be noted. The authors identified criteria used to categorize the mind-body interventions and some readers may disagree with our decisions. We focused this review on mind-body interventions that involved primarily mental activities. Other complementary and alternative medicine strategies not addressed in this review may offer equally or more beneficial effects in treating the pain-fatigue-sleep disturbance symptom cluster. Our study inclusion criteria were meant to be liberal in identifying mind-body strategies that could hold promise in treating the symptom cluster, and as such, we did not evaluate or score study quality as part of this review. Thus, we may have erred on the side of being overly inclusive at this early stage. Similarly, we did not calculate effect sizes to identify relative strength of the mind-body interventions before they have been tested in treating the full symptom cluster.

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Conclusions 

Mind-body interventions such as relaxation, CBT/CST, meditation, music, and imagery may offer benefit to patients with co-occurring pain, fatigue, and sleep disturbance related to cancer. Most patients are capable of using mind-body interventions. Age and advancing disease do not need to be barriers, as the strategies reviewed here require some cognitive, but very little physical effort. Many of the mind-body interventions addressed in this review could be delivered by health-care providers, as social workers, health psychologists, and oncology nurses receive training in cognitive-behavioral coping strategies as part of their educational preparation. Individualized training along with written or audiotaped instructions could be used to evaluate effects on co-occurring symptoms or on a specific symptom cluster.

Although no studies tested mind-body interventions specifically for the pain-fatigue-sleep disturbance symptom cluster, there is sufficient evidence to suggest that relaxation, imagery/hypnosis, CBT/CST, meditation, and music interventions hold promise as crossover treatments that may be efficacious for the full symptom cluster. Studies have shown that relaxation can improve pain and sleep disturbance, meditation can reduce fatigue and sleep disturbance, music can reduce pain and fatigue, and imagery/hypnosis and CBT/CST interventions can produce improvements in all the three symptoms.

A number of unanswered questions about the effects of mind-body interventions on the pain-fatigue-sleep disturbance symptom cluster need to be investigated. To adequately determine if any of the mind-body interventions can be recommended as treatment for the symptom cluster, investigators need to design efficacy studies that select participants based on their experiences of these three symptoms. Researchers need to avoid floor effects by establishing inclusion criteria that allow room to demonstrate improvement in more than one clustered symptom. Studies need to move away from one-group pretest-posttest designs and enhance the quality of evidence by using randomized controlled designs. Because active comparison conditions provide a stringent test, and because patients are not likely to be content “doing nothing” about bothersome symptoms, comparison/control groups should be given careful thought. Eventually, effectiveness trials that make head-to-head comparisons among mind-body strategies will be necessary to determine if one treatment is more effective than another for a particular symptom cluster, or if one treatment can produce the same outcomes at a lesser cost.

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Acknowledgments 

The authors wish to thank Lars Bland for assistance with the initial literature search and Kristen Abbott-Anderson for helpful comments on manuscript drafts.

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Supplementary Material 

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References 

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PII: S0885-3924(09)00793-3

doi:10.1016/j.jpainsymman.2009.05.022

Journal of Pain and Symptom Management
Volume 39, Issue 1 , Pages 126-138, January 2010

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