Depressive disorders and symptoms are common in cancer patients (up to 58% have depressive symptoms and up to 38% have major depression),1-3 worsen over the course of cancer treatment, persist long after cancer therapy,4 recur with the recurrence of cancer,5 and significantly impact quality of life.6-9 Depressive symptom prevalence varies by cancer site, stage, and treatment, as well as by the methods and criteria used in assessing depression.
Unfortunately, clinicians and patients often perceive depression as an expected and reasonable reaction to cancer; as a result, depression is frequently underrecognized and undertreated in oncology practice.10-15 Failure to effectively manage depressive symptoms results from patient, provider, and health system barriers to care. Patients may be reluctant to report symptoms or to see a mental health professional and if treatment is prescribed, they may be nonadherent, citing concerns about side effects and/or preoccupation with active cancer treatment. Providers may be reluctant to raise the issue, be less aware of effective treatment, and/or lack access to mental health professionals.
It is not surprising that low-income patients are particularly unlikely to receive mental health treatment.16,17 In addition, culturally based preferences for depression care can become a barrier if the preferred mode of care is not available.18 Personal culturally based explanations for depressive symptoms may influence symptom expression and patient-provider communication.19-21 Finally, patient perceptions of bias and cultural competence in health care, family perceptions, and practical barriers, such as cost and transportation to therapy, may impede receipt of care.22,23
ASSESSING DEPRESSION AND RELATED SYMPTOMS
Establishing a diagnosis of clinical depression among cancer patients is confounded by biologic and physical symptoms as well as psychological stress attributable to the disease or its treatment.24-27 Cancer and its treatment-related symptoms (fatigue, anorexia, sleep disturbance, and pain) can mask a depression or contribute to its development and persistence.
Difficulty in differentiating the symptoms of depression from those of the medical illness makes the identification and treatment of patients with depression challenging. Indeed, there has been discussion that the presence of depression in medical illnesses such as cancer represents a broader pathophysiologic syndrome known as "sickness syndrome," a behavior or group of symptoms occurring under chronic immune stimulation.28
Assessment of depression should include discussion about common symptoms experienced by patients as well as general distress management,29 and these discussions should continue over the duration of the illness. In fact, a clinical perspective of comorbid cancer and depression is best understood in relation to a staged trajectory of illness from diagnosis to treatment to chronic illness management or "cancer survivorship." Cancer survivorship is a term that has come to represent the state or process of living, following a diagnosis of cancer, regardless of how long a person lives. Thus, treating the patient for depression may be indicated at any stage in the illness trajectory.
The National Cancer Institute (NCI) Web site advises clinicians that "evaluation of depression in people with cancer should also include a careful assessment of the person's perception of the illness, medical history, personal or family history of depression or thoughts of suicide, current mental status, and physical status, as well as treatment and disease effects, concurrent life stressors, and availability of social supports. . . . Suicidal statements may range from an offhand comment resulting from frustration or disgust with a treatment course: 'If I have to have one more bone marrow aspiration this year, I'll jump out the window,' to a reflection of significant despair and an emergent situation: 'I can no longer bear what this disease is doing to all of us, and I am going to kill myself.' Exploring the seriousness of the thoughts is imperative."30
Based on our experience, we would add that it is important to assess potential cultural differences in the patient's personal conceptions of both depression and cancer. For example, many of our Hispanic patients attribute the etiology of depression to life stresses and to cancer-related stress in particular. They also prefer psychotherapy to medication and express the belief that stress can make the cancer worse.
The precise physiologic links between depression and cancer are unknown, although various hypotheses have been discussed in the literature. One of those is dysfunction of the hypothalamic- pituitary-adrenal (HPA) axis. Hyperactivity of the HPA axis is manifested in increased urinary free cortisol levels, dexamethasone nonsuppression, blunted corticotropin response to corticotropin-releasing factor (CRF), increased cerebrospinal fluid CRF concentrations, and adrenal and pituitary hypertrophy.28 Diagnostic findings such as these have been reported in depressed patients with and without cancer.
A few studies have demonstrated that many cancer patients have dysregulation of the HPA axis similar to that of depressed patients without cancer. Evans and colleagues31 found that 40% of their female patients with depression exhibited dexamethasone nonsuppression. However, the small number of studies as well as the limited number of patients studied precludes final determination of the clinical usefulness of dexamethasone suppression testing for all cancer patients with depression.
Several investigators have examined the relationship between HPA axis hyperactivity and immune dysfunction in medically ill cancer patients. Cytokines--hormones that are secreted by cells of the immune system and that act as inflammatory mediators--have been shown to affect neurotransmitter function, neuroendocrine function, and behavior.19 Stress-induced cytokine release or HPA hyperactivity in patients with cancer may cause changes in immunologic function. Proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor can activate the HPA axis, as well as change the metabolism of neurotransmitters such as norepinephrine, serotonin, and dopamine.32 These neuroendocrine and immunologic effects can contribute to the presentation of depressed mood, fatigue, anorexia, pain, or sickness syndrome. Future research in this field has implications not only for diagnosis but more important, for therapy.
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