(PSYCHIATRIC TIMES) - Wouldn't you feel depressed if you had cancer?" This question is one that is often heard from patients, family, and friends as well as from nursing staff and physicians. It may seem logical to expect that someone facing a lifethreatening illness would experience some sadness or depression. However, the problem of depression in cancer patients is a more complex issue. It can span from normal reactions to bad news to clinically significant disorders that can benefit from a variety of treatments. Depression is an important concern in palliative and supportive care, as up to 17% of terminally ill cancer patients have expressed a desire for hastened death. This article will focus on how to recognize depression in cancer patients as well as outline some of the treatment options available to the clinician. Prevalence and Definition Estimates of prevalence for depression vary from as low as 1% to greater than 50%. This wide variation is due to several factors. Different diagnostic assessments, inclusion criteria the reported prevalence of depression. Mental health professionals typically use the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) to diagnose depression. Table 1 lists the symptoms used to make a diagnosis of depression. A person must have either consistently depressed mood or anhedonia in addition to four of the other symptoms listed in Table 1 for at least a 2-week period in order to make a diagnosis of a major depressive episode. Symptoms such as fatigue, weight loss/appetite, and psychomotor retardation can be thought of as the physical or somatic symptoms of depression that are useful criteria in a non-medically ill population. Using these symptoms in cancer patients to diagnosis depression, however, can be problematic, as these physical symptoms are often also associated with treatments for cancer or with the cancer itself. A recent article by Trask outlines several diagnostic approaches that have been used to aid in evaluating depression in cancer patients given this problem. These include the inclusive, etiologic, substitutive, and exclusive approaches. The inclusive approach uses all the criteria of depression regardless of the etiology. The etiologic approach seeks to determine whether a somatic symptom is illness- or treatment-related, or due to depression. The substitutive approach replaces the somatic symptoms of depression such as fatigue with additional cognitive symptoms such as indecisiveness, hopelessness, and pessimism. The exclusive approach excludes the somatic symptoms of fatigue and appetite/weight change that can be seen in many cancer patients. Diagnosis In the clinical setting, a few questions can help determine who may be at risk for major depression and there by prompt referral for further evaluation. Simply asking the patient if he or she is depressed has been shown in one small study to be highly correlated with the presence of major depression.[ 5] Table 2 lists some questions that the clinician can ask to help determine if further investigation or referral is needed.
An important part of any assessment is an evaluation of suicidality. In addition to asking questions about an individual's thoughts of suicide, it is important to keep in mind several factors that are associated with increased risk of suicide. These factors are listed in Table 3. If suicidal ideation is present, the patient should be referred for psychiatric evaluation. In the palliative care setting, it is especially important to consider and assess for suicidal thoughts and the desire for hastened death. Patients with advanced illness are at the highest risk for depression and suicidal ideation. In terminally ill cancer patients, depression and hopelessness were the strongest predictors of a desire for hastened death. Once a clinician has noted a patient's distress, they should try to determine if there are other possible explanations for the symptoms besides a diagnosis of major depression. Several differential diagnoses should be considered when working with cancer patients. Normal Reaction to Bad News
Immediately following bad news, most patients will experience a brief period of distress. Examples of such news would be the initial diagnosis of cancer, the news of cancer spread or relapse, or the news that care will be shifted from a focus on cure to a focus on comfort measures. During these periods, many of the symptoms of depression may be present such as sad mood, decreased appetite, poor sleep, difficulty concentrating, and uncertainty about the future. Patients may be preoccupied with thoughts of death and grieve for their current or anticipated losses. Patients may also experience a sense of helplessness and despair with debilitating symptoms such as pain, nausea/vomiting, and recurrent fevers that necessitate long hospital stays. These feelings are normal and may last for a few weeks depending on the medical and treatment circumstances. After this initial period, most patients will begin to adapt to this new reality and their symptoms will gradually remit. This often takes place as a new cancer treatment plan is undertaken. It is important not to mistakenly label this period as a major depression. This could unnecessarily lead to starting the patient on an antidepressant for symptoms that are limited in duration. It also increases the likelihood of morbidity from medication side effects and drug-drug interactions. An appropriate response to these circumstances is the provision by the oncologist or nurse of brief support and reassurance. The aim of this support is to "normalize" the patient's feelings. This validation can go a long way toward helping alleviate a patient's distress. Adjustment Disorder
When a patient's symptoms of distress do not remit after a couple of weeks and are clearly related in onset to an identifiable stressor such as diagnosis or relapse, a diagnosis of an adjustment disorder should be considered. Many of the symptoms in an adjustment disorder overlap with those of a diagnosis of major depression. The main difference is that in an adjustment disorder, the symptom number or severity will not be great enough to qualify for a diagnosis of major depression. Sometimes an adjustment disorder can progress to a major depressive episode. In cases where the symptoms of an adjustment disorder have persisted for some time or have been quite distressing, a trial of an antidepressant may be warranted. Medical Causes of Depressive Symptoms
Table 4 outlines some of the important medical causes of depressive symptoms, including those related to treatment side effects. In these cases, the patient would be considered to have a mood disorder secondary to a general medical condition. Treatment would involve first attempting to correct the medical cause; however, in many cases, it may also be necessary to utilize psychotropic interventions such as antidepressants.
* Pain-The most common cause of depressed mood in cancer patients is uncontrolled pain. It is also something feared by many patients as they approach death. A commitment on the part of the physician to always work with the patient to control their pain, even if it cannot be completely eliminated, often leads to relief of anxiety for patients. The proper treatment of pain can help to alleviate depressive symptoms.
* Metabolic and Endocrine Abnormalities- Calcium, potassium, and sodium imbalances, as well as thyroid dysfunction and vitamin deficiencies, have all been associated with depression. They are part of the routine screening suggested by mental health providers as part of a work-up to rule out medical causes of depression. Cushing's syndrome, hyperparathyroidism, and adrenal insufficiency have also been associated with depression. There is some evidence that depression has occurred with greater frequency and severity in patients with pancreatic cancer, although the mechanism is not well understood. Some interesting new studies are examining inflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6. The inflammatory cytokines may play a role in the development of depression, specifically in relation to the physical symptoms such as fatigue and sleep and appetite changes.
* Neurologic Abnormalities-Primary brain tumors and brain metastases can produce a variety of symptoms.Right-sided and frontal lesions are particularly associated with mood symptoms.
* Cancer Treatments-Many of the medications used to treat cancer patients can cause depressive symptoms. Particularly common are steroids, such as prednisone and dexamethasone, which are sometimes used as antiemetics prior to chemotherapy agents. Steroids have been known to cause euphoria, irritability, and depression as well as delirium and psychosis. Interferon and IL-2 are also associated with causing depressive symptoms. Chemotherapy agents are known to have many side effects. However, the few agents listed in Table 4 are the ones that have been linked with depressive symptoms. Often stopping the causative agent or reducing the dose can alleviate the depressive symptoms. In cases where there is no alternative, antidepressant therapy may be needed. There is some evidence to show that prophylaxis against depression in these treatment circumstances may be helpful. A study by Musselman found that giving the antidepressant paroxetine prophylactically to patients with melanoma receiving interferon-alpha significantly lowered the incidence of depression when compared to placebo.
* Delirium-Patients who have delirium can present with psychomotor slowing, decreased concentration, crying, and depressed mood. However, a delirious patient will have a generally characteristic rapid onset in addition to a fluctuating course with varying levels of arousal. Delirious patients may also experience visual hallucinations, which are uncommon in depression.
* Dementia-There is usually a history of a slow cognitive decline in patients with dementia as opposed to a more rapid onset of cognitive difficulties coinciding with depressive symptoms in patients with depression. In addition, neuropsychological testing may be helpful to distinguish between depression and dementia, as depressed patients are often able to complete cognitive tasks with significant encouragement.
Management of Depression Once a diagnosis of depression has been made, there are several modalities available to treat these patients. Often a combination of pharmacologic and psychotherapeutic interventions will be utilized. As outlined above, when there is a reversible medical cause such as thyroid function abnormalities, correction of these should be the first focus of treatment. Pharmacologic Treatments
A medication trial is often the primary treatment for depression in cancer patients. However, the use of pharmacotherapy in cancer patients can pose unique challenges. Patients who are at the end of life, possibly entering hospice care, may not be able to wait the 4 to 8 weeks it can take for some of the medications to work at any particular dose. The choice of antidepressant should be based on matching the potential side effects of each medication with the patient's primary symptoms, prognosis, and any comorbid symptoms or conditions. In some cases a side effect such as weight gain or sedation may be beneficial to cancer patients who have difficulty with appetite or sleep. There are five categories of pharmacotherapy that have typically been used in the cancer setting (see Table 5): selective serotonin reuptake inhibitors (SSRIs), atypical antidepressants, tricyclic antidepressants, psychostimulants, and monoamine oxidase inhibitors (MAOIs). The use of MAOIs has greatly diminished in the past few years due to their unfavorable side-effect profile and the numerous drug and food interactions that exist with these medicines. They have been mostly replaced with the now numerous SSRIs and atypical antidepressants on the market that are easier to use and have fewer side effects. The MAOIs are therefore not discussed here further, and do not appear in
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