Neuropsychiatric Syndromes Prevalent Among CNS Cancer Patients

HOUSTON—Approximately 50% to 80% of patients with central nervous system tumors experience emotional and behavioral changes that significantly alter their capacity to function independently and interact in a healthy manner, Alan D. Valentine, MD, said at a symposium on cancer and the central nervous system. In fact, he added, behavioral changes may be one of the first signs that a patient is seriously ill.

“A change in a patient’s behavioral pattern may be the initial sign of a central nervous system tumor,” said Dr. Valentine, of the Department of Neuro-Oncology and the Psychiatry Service at The M.D. Anderson Cancer Center, which sponsored the symposium.

Some behavioral changes, such as fatigue, sleeplessness, and weight loss, are routinely associated with illness; others, such as hallucinations, are more telling of a condition that may require urgent attention, Dr. Valentine said.

Several types of neuropsychiatric diseases are associated with cancer and cancer treatments, he said, and in some cases, the presentations are so similar that misdiagnosis is not uncommon.

The exact psychiatric disorder that will afflict a particular patient depends on a number of factors, including the location of the tumor, the number of tumors, and the rate of tumor growth, as well as the patient’s age and premorbid level of functioning.

Depression Most Common

Some form of depression may be experienced by up to 60% of cancer patients. About 25% of seriously ill cancer patients meet DSM-IV criteria for major depression, Dr. Valentine said. Depression is a common side effect of certain medications and is also highly treatment related, he added.

“Depression is the most common neuropsychiatric diagnosis in cancer patients,” he commented. “We have seen patients fall into depressive states after radiotherapy, chemotherapy, surgery, and biologic response modification. We also know that corticosteroids, opioid analgesics, and anxiolytics can cause mood symptoms.”

Delirium is the second most common neuropsychiatric diagnosis overall and, in the setting of terminal illness, occurs in 50% to 80% of cases. Hallucinations and delusions are common in this patient group, Dr. Valentine noted, as are changes in the patient’s level of arousal, memory, attention, and sleep-wake cycle. Delirium can also agitate or retard the patient’s psychomotor capabilities, which can lead to a misdiagnosis of depression.

Dr. Valentine cautioned that the onset of delirium should be treated as a potential emergency, and the physician should immediately initiate an aggressive search for its origin.

Secondary mood disorders are most often associated with metastatic brain tumors. In addition to depression, the common presentations include behavioral and emotional disinhibition. Said Dr. Valentine: “These patients are normally apathetic and psychomotor retarded. They have difficulty initiating or concentrating on tasks.”

Dementia may be the direct effect of tumor, infection, or treatment side effects, including whole-brain radiotherapy and use of drugs such as ifosfamide (Ifex), methotrexate, and cytosine arabinoside, he said.

Little Progress in Dementia

Dementia associated with a drug side effect may resolve over time; however, dementia caused by disease progression or radiation necrosis is often permanent and can worsen. “Little progress has been made in the management of dementia,” Dr. Valentine said

Accurate diagnosis of neuropsychiatric disorders can be difficult. Given the high probability that cancer patients will experience some form of behavioral change, physicians should maintain a high level of suspicion. Dr. Valentine commented that behavioral testing is an especially helpful diagnostic tool. “Neuropsycho-logic testing may be particularly useful in detecting subtle deficits and differentiating primary and secondary disorders,” he said.

Antipsychotic medications, antidepressants, and other psychopharmacologic treatments are warranted if the patients’ safety is compromised or if the alteration in their functional or emotional state affects their participation in treatment or their ability to perform activities of daily living; however, these drugs must be administered with caution, he warned.

Tricyclics and some atypical antidepressants, such as trazodone, are effective in treating depression but can be sedating. Serotonin uptake inhibitors may be more effective in patients in whom sedation is problematic.

Use Benzodiazepines With Caution

The benzodiazepines are effective in treating secondary anxiety but must be used with caution in treating patients with delirium or dementia.

In some cases, psychotherapy and behavioral therapy including cognitive rehabilitation may be needed to enhance the effects of drug therapy.

Dr. Valentine added that neuropsychiatric disorders can be as problematic for family members and other caregivers as for the patient.

“The caregivers who will support these patients are also at risk of developing depressive and anxiety disorders because of the increased emotional and physical burden they face,” he said. “Physicians would be wise to monitor these individuals and consider appropriate interventions to support them.”