ABSTRACT: The number of older adults in the general population continues to grow. As their numbers rise, the elderly and the management of their medical problems must be of increasing concern for health-care professionals. Within this older population, cancer is a leading cause of morbidity and mortality. Although many studies have looked at the psychiatric implications of cancer in the general population, few studies tackle the issues that may face the older adult with cancer. This article focuses on the detection and treatment of depression, anxiety, fatigue, pain, delirium, and dementia in the elderly cancer patient.
The population of the United States is aging. People who are 65 or older are the fastest growing segment of the US population. As these patients age, they are increasingly having to deal with multiple medical problems. The incidence of cancer in this population is also on the rise.[1,2]
Patients confronted with a cancer diagnosis must face many rigorous treatments, including surgery, chemotherapy, and radiation. With a larger emphasis on outpatient treatment and short hospital stays, people are being asked to participate to a greater degree in their own care and treatment. This is paralleled by an increased interest on the part of patients and families in understanding diagnosis and treatment options and choosing care that matches their values and optimizes quality of life. For the elderly population, the above issues can be particularly problematic.
This article focuses on several psychiatric issues of concern for the elderly cancer patient. Depression, anxiety, fatigue, pain, and delirium are problems that can affect any cancer patient, but can present unique challenges in the elderly population. In addition, the elderly may be contending with cognitive deficits or dementia that can coexist with any of the above problems. Each of these issues alone can adversely impact the care and outcome of these patients. More often than not, however, the elderly are challenged with not just one but a combination of these problems. This article will review these psychiatric issues in relation to the elderly population. We will also discuss some of the treatments designed to manage these problems.
Estimates of depression in cancer patients vary widely and have been reported in some studies to be as high as 50%. Although many early studies of depression in cancer patients included older patients, there was rarely a description of findings based on demographic data such as age. There is some evidence that the risk of depression plateaus from the ages of 65 to 75 but then increases again with advancing age.[4-6]
Risk factors for depression in elderly cancer patients include loss of spouse, functional disability, inadequate emotional support, uncontrolled pain, poor physical condition, advanced illness, previous history of depression, other life stresses or losses, family history of depression or suicide, and medications known to cause depression. Increasing disability and deterioration of health are strong predictors of depression. There is also evidence that depression in the elderly can increase disability, mortality, and the risk of suicide.[7-10]
The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) is the tool used by psychiatrists and other mental health professionals to make a diagnosis of major depression. There are also several instruments used to help in screening for depression in the elderly population, such as the Geriatric Depression Scale and the Center for Epidemiologic Studies Depression Scale. The sensitivity and specificity of these scales are between 70% and 85%. The National Cancer Center Network and the American Cancer Society have recommended the use of the Distress Thermometer. The Distress Thermometer is a visual analog scale that measures distress over the previous week and may be a useful one-item screening tool in conjunction with a Problem List in determining patients who may be suffering from depression.
It is important when assessing any patient for depression to consider a variety of differential diagnoses. Although a cancer patient may respond with an appropriately sad mood in the face of their initial diagnosis or setbacks such as recurrence or failed treatment, it is important to note that a major depression is not a normal part of aging or of having cancer. If a patient's symptoms of depressed mood do not improve after a couple of weeks and are linked to a stressor such as a relapse, the patient may be suffering from an adjustment disorder. In an adjustment disorder, the patient generally has symptoms similar to those of a major depression; however, the symptoms or their severity may be subsyndromal, not meeting criteria for a major depressive episode. If severe enough or long enough in duration, an adjustment disorder may still warrant various treatment strategies, including therapy and medications.
The clinician evaluating an elderly patient must also rule out medical conditions that can cause depression. Metabolic abnormalities such as electrolyte disturbances, vitamin B12 deficiency, or folate deficiency are potential causes of depression. Dysregulation of the hypothalamic-pituitary- adrenal axis and other endocrine abnormalities, such as thyroid dysfunction, decreased growth hormone secretion, or adrenal dysfunction, can also cause depression. In addition, the elderly patient may be taking medications that can cause depressive symptoms. Examples include steroids, interferon, interleukin-2 (IL-2), benzodiazepines, propranolol(Drug information on propranolol), and some antibiotics. Chemotherapeutic agents such as vincristine, vinblastine, procarbazine(Drug information on procarbazine) (Matulane), and asparaginase(Drug information on asparaginase) (Elspar) are also known to induce depression. Physical and cognitive decline and abnormal circadian rhythms have been associated with depressive symptoms.
Pain will be discussed further later on in the article, but in relation to the evaluation of depression, it is the most common cause of depressed mood in cancer patients. Uncontrolled or increasing pain can lead patients to feel that their cancer is progressing. This can add to a sense of despair and hopelessness that puts a patient at risk for suicidal thoughts.
Assessing depressed mood in cancer patients can be difficult, as some of the symptoms of depression such as poor sleep, poor appetite, and decreased energy can be related to the cancer itself or the cancer treatment. These symptoms can be considered the somatic symptoms of depression. Although they can be less reliable for a diagnosis of depression in cancer patients, the elderly tend to have more somatic symptoms of depression than younger patients. Therefore, in addition to the somatic symptoms, the clinician needs to pay special attention to the cognitive symptoms of depression. These include symptoms such as hopelessness, worthlessness, guilt, and suicidal thoughts.
A variety of psychotherapeutic techniques have been used effectively to help the elderly cancer patient suffering from depression (see Table 1). Many of the therapeutic techniques can be utilized to help patients who are suffering from anxiety as well as depression. Supportive therapy can be provided by the patient's primary oncologist and nursing staff as well as by mental health professionals. Supportive therapy seeks to help the patient adapt to difficult and stressful circumstances by supporting strengths and emphasizing positive coping abilities. The aim of supportive therapy is to improve the patient's self-esteem and sense of control. Cognitivebehavioral techniques can be used to help patients reframe negative or pessimistic thoughts by examining those thoughts and attempting to label distortions in thinking that lead the patient to feel more depressed. Once the distorted thoughts are labeled, the clinician helps the patient to find a way to challenge these thoughts with a rational alternative that helps to reduce the patient's level of distress. Individual and group psychotherapies also play an important role in allowing patients to have a safe space to discuss their problems, to receive help in strengthening their coping skills, and to reduce a sense of isolation.
Some of these psychotherapeutic techniques may be hindered in the elderly population in the context of cognitive deficits or physical limitations. It is also important to consider pharmacologic treatment and electroconvulsive therapy (ECT) in depressed elderly patients. It is often the level of distress and functional impairment in depressed individuals that helps determine when a medication will be helpful. Medications are often used in combination with psychotherapy to maximize the benefits of treatment. In general, the same medications used to treat depression in younger patients are effective in the elderly. The difference in treatment is that elderly patients should be started on lower doses of the medications and then dose-titrated more slowly. It is important to note that most of the antidepressant medications can take 4 to 6 weeks for a given dosage to reach a therapeutic effect. Table 2 outlines some of the antidepressant and stimulant medications used to treat depression in the elderly cancer patient.
• Selective Serotonin-Reuptake Inhibitors—The selective serotonin-reuptake inhibitors (SSRIs) are usually the first line of pharmacologic treatment in depression. They are efficacious and are often better tolerated than the older tricyclic antidepressants. The tricyclic antidepressants carry risks that make them more difficult to use in an elderly, medically ill population. Such risks include cardiac arrhythmias, hypotension, sedation, and anticholinergic effects such as urinary retention and memory impairment or confusion. The SSRIs generally have milder side effects which can include gastrointestinal distress, headache, insomnia, or sedation that will often subside over time if the patient continues taking the medication. Many patients can experience sexual dysfunction with the SSRIs, which is problematic if they are still sexually active. In addition, some people may experience anxiety, tremors, or restlessness. Tremors and restlessness could be a potential problem if the patient has a history of Parkinson's disease. Many of the SSRIs are now available in elixir formulations that allow elderly patients who may have difficulty swallowing pills to more easily receive an antidepressant.
The SSRIs are processed through the liver and can therefore have an effect on the P450 isoenzyme system. This may be an important issue for elderly cancer patients who are often on several other medications, increasing the potential for drug-drug interactions. Medications such as fluoxetine that have a long half-life and strong P450 effects may be less desirable in this population. Of the SSRIs, sertraline(Drug information on sertraline) (Zoloft), citalopram(Drug information on citalopram), and escitalopram(Drug information on escitalopram) (Lexapro) may be less likely to cause drug-drug interactions, as they have fewer effects on the P450 isoenzyme system. When a patient has received an SSRI for an extended period of time, it is recommended that the medication be tapered if it is to be stopped. This recommendation is a result of evidence that SSRIs with short half-lives such as paroxetine can be associated with flu-like withdrawal symptoms if discontinued abruptly.
• Atypical Antidepressants—This group of medications includes bupropion, mirtazapine(Drug information on mirtazapine), venlafaxine (Effexor), duloxetine(Drug information on duloxetine) (Cymbalta), and trazodone. Nefazodone(Drug information on nefazodone) has received a black box warning from the US Food and Drug Administration for cases of hepatic failure and is therefore not discussed further due to its rapid decrease in usage.
Bupropion is an antidepressant that appears to work mainly on the dopamine(Drug information on dopamine) system. It tends to be a weightneutral medication and is less associated with sexual side effects than the SSRIs. It also can have a stimulant- like effect that may be helpful for elderly cancer patients with significant fatigue. Bupropion is also approved as a treatment for smoking cessation. Bupropion carries a warning for the potential to cause seizures. This risk appears to be higher for the immediate-release formulation, which is now less commonly used; however, the risk of seizures also increases with increased dosages of bupropion. This risk becomes a concern for patients with a history of seizure disorder, head trauma, central nervous system (CNS) tumor, or an eating disorder.
Mirtazapine is an antidepressant associated with prominent sedation as a side effect. In addition, it is less likely to cause gastrointestinal (GI) distress and often leads to weight gain. These side effects tend to be of use in the cancer population where insomnia, GI distress, and weight loss are prominent concerns. Mirtazapine is also the only antidepressant available in an orally disintegrating tablet form, Remeron SolTab. This tablet dissolves on the tongue and can therefore be given to patients who cannot swallow.
Venlafaxine and duloxetine are both serotonin- and norepinephrinere-uptake inhibitors (SNRIs). The SNRIs are often used when patients do not respond to other antidepressants but can also be used as first-line treatments for depression. Blood pressure monitoring is recommended with venlafaxine, as it has been associated with hypertension as a side effect. Duloxetine is one of the most recent antidepressants released to market; it has also received an indication in the use of diabetic neuropathy, which may indicate additional uses for this medication in pain syndromes.
Trazodone is a highly sedating medication. It is rarely used as a primary antidepressant, as the dose needed for an antidepressant effect would be quite high, and is limited given the sedating side effect. However, this same sedative effect makes trazodone useful at low doses as a nonaddictive sleep aid. Trazodone has been occasionally associated with cardiac arrhythmias and priapism.
• Tricyclic Antidepressants—Although these medications have been around for many years, tricyclic antidepressants can be problematic when used in the elderly cancer patient due to their side effects. Peripheral anticholinergic effects, such as dry mouth and urinary retention, in addition to central anticholinergic effects such as confusion, disorientation, agitation, and memory problems, make these medications more difficult for the elderly to tolerate. Thus, tricyclic antidepressant use has diminished in this population and, if used, the tricyclics are generally given to treat neuropathic pain syndromes. When given for pain, lower doses of the tricyclics can be used. This makes the medication's use safer and more tolerable.
• Psychostimulants—These medications offer an additional approach to the treatment of depressive symptoms in the elderly cancer patient. They are most helpful in patients where the depression is accompanied by symptoms of psychomotor slowing, decreased energy, decreased motivation, and apathy. In relatively low doses the stimulant medications have been shown to decrease feelings of fatigue in cancer patients and promote a sense of well-being as well as to increase appetite. They are often helpful to combat the sedating side effects of the opioid pain mediations.
• Monoamine Oxidase Inhibitors (MAOIs)—The clinical use of the MAOIs has declined with the availability of the SSRIs and atypical antidepressants, which are associated with far fewer side effects. The MAOIs are associated with the greatest number of drug-drug interactions and carry a risk for a hypertensive crisis if combined with the wrong food or medication, and are not discussed further here.
• Choosing an Antidepressant—In addition to the information listed above, one should always consider the patient's personal and family history. If a patient has a past psychiatric history of a good response to a medication or if a family member takes a particular medication, it is a good rule of thumb to look to this medication as the first consideration for current treatment. In addition, factors such as overall health and cognitive abilities need to be weighed when considering the patient's ability to take a medication on a consistent basis. Financial considerations may also play an important role in medication selection. Some of the medications, such as fluoxetine(Drug information on fluoxetine), paroxetine(Drug information on paroxetine), and methylphenidate(Drug information on methylphenidate), have been on the market for many years and are available in generic forms. These generic forms are generally less expensive and may therefore be more affordable for patients than medications like duloxetine or modafinil(Drug information on modafinil), which are only available under their brand names at higher costs.
Other considerations include a comorbid history of anxiety, pain, substance abuse, or psychosis. For example, a patient with a history of anxiety and insomnia may do better with a calming medication such as mirtazapine, whereas a patient with fatigue and sedation may do better with a stimulating antidepressant such as fluoxetine, bupropion, or a stimulant. A patient with depressive symptoms who is also attempting to stop smoking may be helped by bupropion.
• Electroconvulsive Therapy—Electroconvulsive therapy is an extremely effective antidepressant treatment. It is also surprisingly safe in elderly patients. Relative contraindications may include CNS masses or severe cardiac problems. Electroconvulsive therapy may in fact be a more useful antidepressant strategy for those patients who cannot tolerate medications or whose cancer treatments interact with available antidepressant medications. It is also helpful for patients who are refractory to multiple trials of antidepressant medications from different classes. Although there is still a stigma attached to the idea of ECT for many patients, the procedure is generally well tolerated. It is usually performed with the help of an anesthesiologist and continues to be improved upon. The main side effect of ECT is short-term memory disturbance. Unilateral ECT is associated with a lower incidence of cognitive effects than bilateral ECT.