The number of older adults in the general population continues togrow. As their numbers rise, the elderly and the management of theirmedical problems must be of increasing concern for health-care professionals.Within this older population, cancer is a leading cause ofmorbidity and mortality. Although many studies have looked at the psychiatricimplications of cancer in the general population, few studiestackle the issues that may face the older adult with cancer. This articlefocuses on the detection and treatment of depression, anxiety, fatigue,pain, delirium, and dementia in the elderly cancer patient.
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, and some antibiotics. Chemotherapeutic agents such as vincristine, vinblastine, procarbazine (Matulane), and 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.
Therapeutic Strategies for Treating Depression and Anxiety in Elderly Cancer Patients
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.
Useful Medications in Treating Depression in Elderly Cancer Patients
• 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 (Zoloft), citalopram, and 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, venlafaxine (Effexor), duloxetine (Cymbalta), and trazodone. 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 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, paroxetine, and 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, 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.
Anxiety is experienced by most cancer patients at some point during the course of their diagnosis and treatment. It is often seen at crisis points such as the initial diagnosis or discovery of a relapse after treatment. This anxiety can often be viewed as a normal reaction to a stressful and traumatic event. There can even be a positive effect of anxiety in motivating someone to gather information and support that helps to inform decisionmaking. It can therefore be difficult to determine when a patient's anxiety lies out of the normal range and requires specific intervention. In general, anxiety that persists beyond the immediate period of a stressor and anxiety that causes impairment in functioning should prompt further evaluation. Anxiety may also be a component of pain, delirium, and depression. Anxiety is not well studied in the geriatric cancer population. In patients with cancer the prevalence of anxiety ranges from 21% to 28%.
Symptoms of anxiety may be grouped, as are depressive symptoms, into both cognitive and somatic symptoms. The cognitive or psychologic symptoms can include fear of death, loss of control, thoughts of impending doom, overgeneralizing, and catastrophizing. The somatic symptoms are often found in panic attacks and can include tachycardia, shortness of breath, diaphoresis, gastrointestinal upset, nausea, trembling, and dizziness.[16,17]
The differential diagnosis of anxiety in the elderly cancer patient can be a difficult undertaking as several factors may interact to contribute to anxiety. Patients who are in pain may appear anxious and agitated. When their pain is adequately treated, patients usually experience a marked reduction in anxiety. Patients with respiratory problems such as lung cancer or patients in respiratory distress can present with anxiety and restlessness. This anxiety can set off a cycle of worsening shortness of breath followed by more anxiety. An acute event such as a pulmonary embolus may also initially present with someone who appears quite anxious. The symptoms of anxiety in these cases may respond initially to an anxiolytic medication, but the patient's anxiety ultimately will respond to proper medical intervention. Sepsis, endocrine abnormalities, hypoglycemia, hypercalcemia, and hormone-secreting tumors may all be associated with anxiety symptoms. There is some evidence that depression, anxiety, and panic attacks can occur in patients with pancreatic cancer, although the mechanism is not entirely clear.
Several medications or treatments are associated with anxiety. Examples include medications used for their antiemetic properties. Steroids such as dexamethasone and other antiemetics such as prochlorperazine and metoclopramide can cause anxiety or akathisia-a motor restlessness accompanied by subjective feelings of distress and hyperactivity. In addition, withdrawal from alcohol or benzodiazepines is associated with anxiety.
The DSM-IV describes a variety of anxiety disorders. A patient may have a preexisting anxiety disorder or may develop an anxiety disorder after a cancer diagnosis. The spectrum of anxiety disorders includes such diagnoses as generalized anxiety disorder, panic disorder, and posttraumatic stress disorder. It also includes phobias like a fear of needles and claustrophobia. These may have great impact on cancer patients who must undergo multiple tests and procedures such as magnetic resonance imaging, injections, and intravenous treatments. An anxiety response may also be conditioned. Patients may have anxiety symptoms emerge as an anticipatory response to a repeated aversive treatment such as chemotherapy.[16,19] Diagnosis is often made on the basis of clinical interview, but some screening tools such as the Hospital Anxiety and Depression Scale-which does not have items for the somatic symptoms- can be useful.
Medications Used for Anxiety in Older Cancer Patients
Anxiety is distressing to the patient and often can interfere with necessary procedures and treatments. Therefore, even milder forms of anxiety should be addressed. Patients may benefit from several cognitive-behavioral interventions. These include such techniques as meditation, guided imagery, progressive relaxation, biofeedback, hypnosis, and reframing negative, irrational thoughts. In addition, other psychotherapeutic techniques such as insight-oriented, supportive, and group therapy may help reduce anxiety. The use of medications to treat anxiety in the elderly cancer population should be approached carefully. In a younger population, benzodiazepines may be one of the first lines of treatment. In an elderly population, the clinician may want to try alternative medications first and use lower doses if needed (see Table 3).
• Benzodiazepines-This class of medications is often useful in treating anxiety and may be helpful in some elderly patients; however, their use must be accompanied by great caution. The most common side effects of these medications are sedation and confusion. These effects occur more frequently in the elderly and in those with impaired brain or liver function. The longer-acting benzodiazepines such as diazepam tend to build up over time and are therefore more likely to cause sedation and confusion. Many benzodiazepines, such as diazepam, clonazepam, and alprazolam, are processed through oxidation which, in addition to other factors in the elderly, can cause them to have a longer half-life. Lorazepam, oxazepam, and temazepam are conjugated but not oxidized by the liver, making them better tolerated by the elderly as well as patients with impaired hepatic function. However, these medications must still be monitored closely in those with renal dysfunction.
With all benzodiazepines, side effects such as drowsiness, confusion, and motor incoordination must be monitored carefully. One of the greatest morbidities from these medications is their potential to cause imbalance in the elderly patient, which can lead to falls. Often these patients will be on other medications that have CNS effects, such as opioids for pain management. It is important to monitor these medications as they may have a synergistic CNS depressant effect. Patients with dementia or brain injury who are treated with benzodiazepines may have a paradoxical reaction and become disinhibited, irritable, or agitated.
• Antidepressants-Many of the antidepressants listed in Table 2 are also useful in the treatment of anxiety disorders. Unlike the benzodiazepines, however, they may take several weeks to become effective at any given dose. Often, clinicians who start a patient on an antidepressant medication for anxiety will also give the patient a low-dose benzodiazepine for the first few weeks of treatment. This helps to treat the patient's anxiety until the antidepressant has had a chance to become effective. Once the antidepressant is working, the benzodiazepine can be tapered and discontinued. In general, stimulants and stimulating antidepressants (ie, methylphenidate or bupropion) should be avoided in patients suffering from severe anxiety, as they can tend to worsen it.
• Buspirone-Buspirone is a nonbenzodiazepine antianxiety medication. It can be a helpful anxiolytic in the elderly. However, similar to many of the antidepressants, it must be taken daily and can take several weeks before the patient experiences benefit from this medication. It is usually well tolerated by patients but has been seen as ineffective by some clinicians due to underdosing.
• Neuroleptics-When patients cannot tolerate benzodiazepines or when their anxiety is not well controlled on a benzodiazepine, the use of a lowdose atypical antipsychotic (neuroleptic) can be quite helpful. Atypical neuroleptic medications do not have the same potential effects on respiration, and although some are sedating, they tend not to cause confusion in the elderly. This may be beneficial for patients taking narcotic pain medications, as the neuroleptic may serve as a buffer against the cognitive side effects of the opioid whereas a benzodiazepine might make these effects worse. The newer atypical antipsychotics such as olanzapine (Zyprexa), risperidone (Risperdal), and quetiapine (Seroquel) may be preferred to the typical antipsychotics such as haloperidol.
The atypicals tend to be more easily tolerated and in low doses are less associated with akathisia (motor restlessness) than the older typical neuroleptics. Some of the atypicals such as olanzapine have been associated with the potential for weight gain and the development of diabetes, whereas other atypicals such as aripiprazole (Abilify) and ziprasidone (Geodon) have not been associated with these effects. Aripiprazole and ziprasidone are the newest atypicals and are associated with less sedation. It is not yet clear whether these medications have any benefit in helping with anxiety.
Fatigue is a common symptom in the elderly cancer patient. The prevalence of fatigue in patients with advanced cancer has been estimated in some studies to be greater than 50%.[1,21,22] A study published by Respini et al examined fatigue in the elderly cancer patient and found that it was almost universal in their sample. In 84% of the cases in their study, the patient's fatigue interfered with his or her general level of activity. Fatigue also tended to be correlated with anemia and depression.
Unlike depression and anxiety, fatigue does not have well-defined syndromes and diagnostic criteria in the DSM-IV. The assessment of fatigue can be made in the clinical setting by using simple verbal (mild, moderate, severe) or numeric (0-10) severity scales. There are several fatigue assessment measures that have been used and validated, but they have generally not been tested specifically in the elderly cancer population. An example of these measuring tools is the fatigue symptom inventory used in the Respini et al study. It measures the intensity, frequency, and disruptiveness of fatigue on a 14-item scale with a rating of 0 to 10 for each item. Other examples include the Brief Fatigue Inventory and the Multidimensional Fatigue Inventory.[24,25]
It is also important to assess other potential causes or correlates of fatigue. In the process of evaluating fatigue, assessing a patient for comorbid pain and depression is essential. A careful review of the patient's medications and routine bloodwork to check for anemia, electrolyte disturbance, or thyroid dysfunction can all prove helpful. Inflammatory cytokines that are being investigated as correlates of depression may also play a role in the development of fatigue.
Treatment of fatigue in the elderly cancer patient is not well studied. The first approach should generally be to address any potentially identifiable etiologies. The clinician should aim to treat any metabolic or electrolyte abnormalities. For example, blood transfusions or administration of erythropoietin can be used to treat anemia. Correlates such as depression or insomnia should be addressed.[1,26,27]
Exercise has been used as a treatment for fatigue in cancer patients receiving chemotherapy, but has not been well studied as a treatment for fatigue in elderly cancer patients. In theory, it could be helpful in improving and maintaining energy level as well as maintaining functional status in an elderly population. As is a general rule with medications, any exercise plan should be started slowly with a gradual increase over time.
Medications have been used to try to help treat fatigue in cancer patients. Again, study of the elderly cancer population is limited. Psychostimulants such as methylphenidate or modafinil have been used successfully for cancer- related fatigue. Modafinil may be a gentler, better tolerated medication for the elderly. Antidepressants with some stimulating effects such as bupropion or fluoxetine may be helpful to improve energy, especially when there are also concomitant symptoms of depression.
Pain is experienced by 50% to 90% of patients with advanced cancer. Pain is also a frequent complaint of the elderly. There is no evidence that pain perception in the elderly is diminished in any way; however, pain tolerance may decrease in older adults.[30,31] In addition, the elderly are more likely to have pain than their younger counterparts. Despite these facts, elderly patients are at risk for the undertreatment of their pain. Risk factors to inadequate pain management include underreport by the patient, underestimation of sensitivity to pain on the part of the clinician, inadequate pain assessment, and clinician as well as patient fear that an opioid pain medicine will not be tolerated or will be addictive.[31,33]
The consequences of inadequate pain control can include depression, anxiety, suicidal ideation (even in the absence of depression), insomnia, increased isolation, and immobility. Immobility in the elderly can lead to deconditioning and overall functional decline. This can then lead to a greater risk of falls and deep vein thrombosis development.[31,34]
The patient's subjective report is often the primary method for assessing pain. Clinicians usually assess pain on the basis of location, character, intensity, radiation, and frequency.[ 35] Pain assessment tools may be helpful in assessing the intensity of pain. There are several scales that have been used, such as the pain thermometer, the verbal descriptor scale, and the visual analog scale. These scales are unidimensional, however, and do not take into account certain aspects of a patient's pain experience. Other scales such as the Memorial Symptom Assessment Scale include various symptoms. Bruera outlines a multidimensional "production-perception- expression" model of symptoms that also takes into account affective issues such as depression and anxiety as well as psychosocial factors and cancer-related symptoms.[ 35,37] The assessment of depression and anxiety is particularly important in looking at the pain response as there is evidence that treatment for related symptoms such as depression can facilitate pain management.[ 32] The assessment process may take longer for elderly patients than for their younger counterparts. The main objective is to choose a tool and then consistently use it to ensure reliable assessments.
There are often barriers to evaluating pain in elderly cancer patients. Cognitive deficits seen in dementia and delirium or visual and hearing impairments may make the assessment of pain more difficult. Speaking with the patient's family and caregivers may be essential in these cases. These patients may appear depressed or exhibit crying, irritability, and social withdrawal but not be able to clearly describe their pain. Attention to facial expressions and muscle tension may lend clues to whether a patient is in pain but are relatively nonspecific. The evaluation of pain in patients with these types of impairments requires further study.
• Nonpharmacologic Techniques-Whenever possible, nonpharmacologic techniques should be employed to help treat pain. They can improve overall pain treatment by reducing the amount of pain medication needed and thereby reduce the likelihood of adverse drug effects.
Physical techniques such as massage, exercise, thermal treatments, and acupuncture can all help a patient to relax and be distracted from their pain. In addition some treatments such as acupuncture and transcutaneous electrical nerve stimulation are associated with the release of endogenous opioids in the brain.[30,38,39]
Cognitive-behavioral therapies can also help patients to relax and turn their focus away from their pain, helping to reduce its perceived intensity. These interventions can range from teaching patients relaxation techniques, guided imagery and meditation to using music and art therapy.
• Pharmacologic Management-Pain should be treated as aggressively in elderly cancer patients as it is in younger patients. Some of the medications used to treat pain include acetaminophen and salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, cyclooxygenase-2 (COX-2) receptor inhibitors, and opioids. Several factors may impact the dosing and use of medications. As people age, they have a general decline in hepatic and renal function that may decrease the metabolism and clearance of certain medications. The elderly also have differences in plasma protein binding and body fat to muscle ratio that impact the distribution of medications. In general, clinicians will often start at lower doses of medications in the elderly.
Acetaminophen is the preferred agent for mild pain in older adults. It is also often combined with other agents such as opioids to treat more severe pain. Acetaminophen works in the CNS and does not have an antiinflammatory effect. It is metabolized by the liver, so care must be taken when prescribing it to patients with hepatic impairment.
The NSAIDs are a mainstay of pain treatment in the general population. The elderly, however, are at greater risk of adverse renal toxicity from this class of drugs. The NSAIDs are also associated with an increased risk of peptic ulcers and GI bleeding. The COX-2 inhibitors have been an alternative to the NSAIDs and were initially thought to have less risk of GI side effects. However, the usefulness of these medications for the elderly is now somewhat in question with the removal of rofecoxib (Vioxx) from the market in September 2004. Rofecoxib was removed due to an increased risk of cardiovascular events such as heart attack and stroke.
The World Health Organization created a set of guidelines in the 1980s to improve the treatment of cancer pain. These guidelines provide a threestep analgesic ladder that progresses depending on pain intensity from the NSAIDs and acetaminophen for mild to moderate pain to the opioids and analgesic combinations for severe pain. Although this ladder is quite useful in the general cancer population and even in noncancer patients, it must be tailored somewhat when dealing with older adults. For example, the American Geriatric Society has recommended that opioids be substituted for NSAIDs for mild to moderate pain in the elderly given the increased potential for toxicity with the NSAIDs in this population.
Opioids provide relief of pain in 75% of cancer patients and should be a first line of treatment in moderate to severe cancer pain. Side effects of the opioids include constipation, sedation, and respiratory depression. Patients may also develop tolerance to the effects of opioid medications over time.
There are also several adjuvant medications used to treat pain. Several antidepressants, most notably the tricyclics, have been used as adjuvant treatments for pain, especially neuropathic pain. Some newer atypical antidepressants, such as duloxetine, which is approved for diabetic neuropathy, are also being used to treat pain syndromes. Other agents include steroids such as prednisone, anticonvulsants such as gabapentin, and topical agents such as capsaicin. When prescribing analgesics for the elderly cancer patient, it is wise to use drugs that have a short half-life, if available. It is best to begin by prescribing one drug at a time and carefully monitoring for additive effects. As with all medications in the elderly it is good to start with low doses, and make sure to continue a drug trial for an adequate duration.
Delirium is characterized as a disturbance in attention or level of arousal as well as a disturbance in cognition. The disturbance generally develops over a short period of time (hours to days) and fluctuates during the course of the day.
The elderly are particularly susceptible to the development of delirium. An estimated 30% to 50% of patients over the age of 70 have been shown to demonstrate symptoms of delirium at some point during a medical hospitalization.[43-47] Additionally, elderly patients who develop delirium during a hospitalization have an estimated 22% to 76% chance of dying during that admission. Major risk factors for delirium appear to be preexisting cognitive impairment, advanced age, and severity of comorbid medical illness.
The etiology of delirium in cancer patients is often multifactorial. Delirium can be caused by the direct effects of cancer on the CNS, or by more indirect effects of the disease or its treatments. Examples of such indirect effects include medications, electrolyte or other metabolic imbalance, paraneoplastic syndromes, and preexisting cognitive impairment or dementia.
Medications and chemotherapy agents are a common cause of delirium. Given the large number of medications that an older person may already be taking, any addition to the list may be enough to cause a delirium. Examples would be routinely ordered hypnotics such as zolpidem (Ambien) or narcotic analgesics used to treat pain. Chemotherapeutic agents that have been associated with delirium include methotrexate, fluorouracil, vincristine, vinblastine, bleomycin, carmustine (BiCNU), cisplatinum, asparaginase, procarbazine, ifosfamide, and the glucocorticosteroids.[49-53] Other immunotherapeutic agents such as IL-2 and interferon or anti-infectious agents such as amphotericin B and acyclovir can also cause delirium.
The Mini-Mental State Examination (MMSE) is a useful screening tool for cognitive impairment but does not distinguish between delirium and dementia. The MMSE can provide a quantitative assessment of the severity of cognitive deficits and is sensitive in detecting cortical dementias such as Alzheimer's disease. The Confusion Assessment Method, the Delirium Rating Scale, and the Memorial Delirium Assessment Scale are other tools that can be used in the assessment of delirium.
Neuroleptics That May Be Useful in Managing Delirium in Elderly Cancer Patients
The management of delirium in elderly cancer patients involves addressing the symptoms of the delirium while investigating and ultimately treating its underlying causes. Nonpharmacologic interventions such as providing a structured and familiar environment can help reduce anxiety and disorientation. These interventions include a quiet, well-lit room, a visible clock or calendar, and the presence of family to provide reassurance. Often these supportive interventions will not be effective enough on their own and symptomatic treatment with neuroleptic or sedative medications will be necessary. Continuous observation by nursing staff, and in severe cases, restraints, may also be indicated.
Table 4 lists some neuroleptics that can be used to treat the symptoms of delirium. All neuroleptics carry a risk of tardive dyskinesia and neuroleptic malignant syndrome; however, the newer atypical antipsychotics are thought to be less likely to cause these adverse effects. It is also prudent to periodically monitor a patient's electrocardiogram during treatment with a neuroleptic, as most can prolong the QTc interval to some degree. Haloperidol and chlorpromazine are typical neuroleptics that can be used intravenously, providing some advantage in delirious patients who are agitated or unable to take oral medications. Haloperidol is an example of a high-potency neuroleptic that can be associated with extrapyramidal effects such as akathisia or cogwheeling and torsades de pointe. Acute dystonia is rare in the elderly. Haloperidol is still considered the drug of choice in the treatment of delirium.[55-58]
Chlorpromazine is an example of a low-potency neuroleptic that can be associated with anticholinergic effects, orthostatic hypotension, akathisia, cardiac effects, and sedation. A common strategy in the management of an agitated delirious patient is to add parenteral lorazepam to a regimen of haloperidol. This combination may be more effective in rapidly sedating an agitated patient. Lorazepam alone is generally ineffective for delirium and in one study contributed to a worsening of delirium and cognitive impairment.
The newer atypical neuroleptics are increasingly used to manage delirium, as they tend to have fewer side effects. Quetiapine, olanzapine, and risperidone have some sedating properties, with quetiapine being the most sedating of the three. These agents may also be associated to varying degrees with the development of increased blood sugar, increased lipids, and weight gain. Ziprasidone and aripiprazole appear to be less sedating and less associated with the metabolic changes of the other atypicals. Olanzapine and risperidone are now available in orally disintegrating tablet forms that dissolve easily on the tongue. Olanzapine and ziprasidone are also now available in intramuscular formulations.
The choice of a neuroleptic is often made by considering the patient's prominent symptoms as well as the side-effect profile of each medication. For example, in an agitated delirious patient a combination of haloperidol and lorazepam can be used. Alternatively, a sedating agent such as chlorpromazine or olanzapine may be helpful in the hyperaroused delirious patient. Benefits of these medicines in patients over 70 are not clear, as in at least one open-label trial of olanzapine for delirium increased side effects and decreased beneficial effects were found in this age group. For a hypoaroused delirious patient, haloperidol, risperidone, or ziprasidone may be a better choice. If the patient refuses or is unable to swallow a medication, intravenous haloperidol or the orally disintegrating tablet forms of risperidone and olanzapine may be preferred.
There are an estimated 1.8 million elderly individuals in the United States who have advanced dementia requiring extensive care. Patients with severe dementia often exhibit emotional and behavioral disturbances that make their care more difficult.
Dementia is defined in the DSMIV as the development of multiple cognitive deficits manifested by both memory impairment and cognitive disturbances. The cognitive disturbances can include aphasia, apraxia, agnosia, and disturbances in executive functioning (such as planning or organizing). Alzheimer's dementia accounts for 60% to 70% of all patients with dementia. Another 15% to 25% of patients have vascular dementia and approximately 10% to 15% will have a mixed dementia. The remaining patients have other diagnoses such as Parkinson's disease, Lewy body disease, and frontal-temporal dementia.[62,63] Dementia has also been noted to develop secondary to cancer treatment. For example, dementia has been reported following radiotherapy of brain tumors when administered alone or in combination with nitrosourea-based chemotherapy.
Cognitive impairment in cancer patients often goes unrecognized, yet it is of great importance in relation to issues of capacity and decision-making in older adults. A diagnosis of dementia does not automatically determine a lack of capacity. However, when cognitive impairment is identified, it should prompt further evaluation. Often a psychiatric evaluation will be necessary to determine the patient's ability to participate in the decision-making process. The psychiatrist looks for evidence that the patient can both understand and retain information related to a specific decision or circumstance. This ability allows the patient to make an informed decision. When a patient is deemed not to have capacity, a health-care proxy must be determined. Given the potentially poor quality of life for an older cancer patient with dementia, careful consideration should go into the extent of aggressive treatment that should be pursued in a patient with severe cognitive deficits.
Definitive assessment of dementia is often difficult as the most common form of dementia, Alzheimer's disease, is usually made as a diagnosis of exclusion. The confirmatory diagnosis is generally made after a person's death at autopsy. Routine screening should be done to rule out the few reversible causes of dementia such as vitamin B12 deficiency. However, most cognitive assessment is done for the purpose of determining functional and decision-making capabilities. To that end, the previously mentioned MMSE is commonly used to assess a patient's level of cognitive functioning. Although performance may be affected by certain social and educational factors, a score of 24 or less out of 30 is suggestive of cognitive dysfunction.
With the exception of certain endocrine and metabolic abnormalities, most forms of dementia are not reversible. There are several medications that have been approved to slow the cognitive decline of dementia and postpone the need for nursing home placement. Such medications include the acetylcholinesterase inhibitors like donepezil (Aricept) and the newer N-methyl-D-aspartate receptor antagonist memantine (Namenda). Additionally, neuroleptic medications may be used to help control the behavioral and psychotic symptoms that can develop in advancing dementia.
When considering dementia in the elderly cancer patient, one of the most important factors is to distinguish dementia from delirium. This can be a difficult task as the two frequently share impairment in memory, thinking, and judgment as well as disorientation. Further complicating the issue, patients with dementia can develop a superimposed delirium. However, dementia tends to appear in relatively alert individuals without a clouding of consciousness. Patients with dementia tend to have a more stable set of deficits at any given time as opposed to the fluctuating symptoms seen throughout the course of a day in delirium. The onset of symptoms in dementia is also slower with a chronically progressive decline in cognitive function, rather than the relatively rapid onset of symptoms seen in delirium.
The assessment and management of issues facing the elderly cancer patient are of increasing concern to both oncologists and mental health professionals. As cancer treatments become more aggressive and successful, and as the population of older adults with cancer grows, the impact on the quality of life of older patients continues to be increased. This article highlights some of the important areas of distress that the older adult with cancer may contend with during their illness to aid in assessment and diagnosis.
Depression, anxiety, fatigue, pain, delirium, and dementia are all complex problems that require further study in the elderly cancer population. Various psychotherapeutic and psychopharmacologic interventions aimed at helping these patients were reviewed. The goal of identifying and treating these distressing problems is to improve the overall quality of life for people living with cancer.
Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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