21 October 2013

Symptom Clusters: Pain, Depression, and Fatigue

JNCI Monographs 2004 2004(32):119-123; doi:10.1093/jncimonographs/lgh028

There is not yet sufficient evidence-based experience for the coordinated treatment of three symptoms that cluster in cancer: pain, depression, and fatigue. Each symptom taken individually has accepted treatment modalities. With some overlap between these symptoms, established treatments for one symptom may "cross-over" and reduce the burden of one, or both of the others. To optimize patient care in advance of the evidence basis, attention to these symptoms is value-added for patients and their families. Standardized screening using the Distress Thermometer for physical, practical, emotional, or spiritual symptoms helps effectively identify patients whose symptoms warrant attention. Cancer Supportive Services, an innovative program at the Continuum Cancer Centers of New York at Beth Israel and St. Luke’s-Roosevelt, provides comprehensive intervention throughout the trajectory of care for pain, depression, and fatigue. These services are provided in tandem with efforts to cure or contain the cancer. Cancer Supportive Services sets up a natural entry point to survivors’ follow-up or end-of-life care. Such an effort reinforces a basic principle that active symptom management is integral to each patient encounter in the cancer treatment setting.


There are many dimensions to patients’ experience with cancer. Certain experiences, or symptoms, are shared by most patients with cancer. As discussed elsewhere, three of those symptoms, pain, fatigue, and depression often track together in the same individual. Taking the type of cancer, stage, and treatment into account, subjective evaluation of these predictable commonalities is colored by the extent to which his or her cancer can be treated or cured, individual psychology, and effective social or spiritual support.

Until the recent past, these symptoms were silently tolerated as a consequence of cancer and its treatment. If identified at all, they were considered as part of the burden one pays when living with life-threatening illness and perhaps as surrogates for the extent of disease or treatment response. Modern biotechnology, and the extended survival of patients with some cancers, has brought focus to these symptoms and expanded the opportunity for intervention. The strengthened sense of consumerism coupled with faster multimedia communications’ information explosion have sparked demand for the treatment of pain, fatigue, and depression before rigorous studies of the triad have been completed.

The question at hand—What is the optimal treatment of symptom clusters?—challenges the underpinnings of medical decision making developed throughout the twentieth century as well as the notion of evidence-based medicine popularized at the century’s close. Accurate diagnoses, made with uniform and accepted criteria in mind, precede the formation of a treatment plan. Treatment, when instituted, is based on evidence from controlled trials as the gold standard taking precedence over clinician familiarity or past experience.

Separating the constitutional signs and symptoms of cancer itself from those of depression has become more feasible through collective experience and research, though the process is still somewhat inexact. Challenging the popular notion that all cancer patients suffer depression has led to a dilemma: defining degrees of depression in the wide variety of cancer illnesses at its various stages and with its confounding treatments, and then designing proper treatment for these mood changes. Tradition asks that a diagnosis be established before a treatment plan is set. Estimating the contribution of mood to the experience of cancer underscores the very basic property of mood as a background emotion to the life experiences that occur around it.

With a parallel interest in diagnosing and treating pain and fatigue, the ever-present contribution of mood complicates the understanding of these symptoms in cancer. Not every patient experiences pain or fatigue to the same degree, and culture and personal values overlay these symptoms as well. Looking at each symptom separately, it should be clear that their presentation and measurement have substantial overlap, so it is reasonable to assume that respective treatments would overlap as well.

Critical thinking forces us to first look at accepted treatment modalities for each symptom in isolation, drawing on what is known about the symptom in general: depression in the physically healthy, fatigue in those without depression or cancer, and pain from a variety of causes. The subsequent challenge is to adapt these "pure" circumstances across the spectrum of cancer and its treatments, adjusting for age and comorbidities.

With an evidence-based focus, the next step to approaching the treatment of symptom clusters is to survey published data examining cluster treatments across the lifespan and among various cancers. Articles describing findings of these clusters do not exist. An innovative methodological adaptation is to take the usual and generally acceptable treatment modalities used for a single cancer symptom and examine its efficacy in the remaining two symptoms. The notion of "clustering" of pain, fatigue, and depression is born out of the impression that a treatment modality commonly used in one symptom can reduce the burden of the others.

© 2004 by Oxford University Press

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