Delirium, Dementia, Apathy Require Individualized Treatment

WASHINGTON, DC-Comorbid neuropsychiatric conditions in elderly cancer patients, which commonly occur but are underdiagnosed, should be identified and treated to improve quality of life, according to clinical psychologist Margaret Booth- Jones, PhD. Reporting at the first annual Geriatric Oncology Consortium multidisciplinary conference, entitled "Advancing Cancer Care in the Elderly," Dr. Booth-Jones said delirium, dementia, and apathy are just several neuropsychiatric changes that can impact the patient's personality, sense of self, and independence. "Anything that does this is a real threat to who we are, and dramatically affects quality of life, not only for the elderly patient, but for family members and loved ones," said Dr. Booth- Jones, assistant professor of psychosocial and palliative care, H. Lee Moffitt Cancer Center, Tampa, Florida. Treatment needs to be individualized, she said, based not only on the cause of the neuropsychiatric condition, but also on the basis of each elderly patient's symptoms, organ function, and other medical comorbidities. Treatment must be reassessed frequently-as often as once weekly- and modified as required until the patient receives optimal benefit. Delirium Determining the etiology of the neuropsychiatric disorder may require a careful patient assessment. Delirium, for example, can have a number of causes, including drug intoxication or withdrawal, sleep deprivation, cardiovascular disease, or an underlying metabolic disorder. Delirium in the elderly is usually of sudden onset, and it may be misiden-tified as dementia or depression. In addition to typical symptoms such as disorientation, consciousness disturbance, and waxing/waning alertness, the elderly patient may become paranoid. "This can be very stressful for the caregiver or family," Dr. Booth- Jones said. Delirium often can be managed nonpharmacologically using intervention protocols that target specific risk factors for the neuropsychiatric condition. For example, clinicians can target sleep deprivation with protocols that encourage or enhance rest, while cognitive impairment can be addressed with protocols that emphasize orien-tation or therapeutic activities (Ann Intern Med 135:32-40, 2001). Multiple pharmacologic treatments have been tried in delirium. In one double-blind trial of hospitalized AIDS patients, investigators found that low doses of neuroleptics (chlorpromazine and haloperidol(Drug information on haloperidol) [Haldol]) were effective and produced few adverse events. On the other hand, a benzodiazepine (lorazepam) was not effective and produced enough treatment-limiting side effects that investigators terminated that arm of the study (Am J Psychiatry 153:231-237, 1996). In an open trial, although olanzapine(Drug information on olanzapine) (Zyprexa) was determined to be "clinically efficacious and safe" for treating delirium in hospitalized medically ill patients, age greater than 70 years was a factor associated with poorer outcome (Psychosomatics 43:175- 182, 2002). Other drugs tried for delirium include methylphenidate(Drug information on methylphenidate) (Concerta,Methylin, Ritalin), droperidol(Drug information on droperidol) (Inapsine), quetiapine(Drug information on quetiapine) (Seroquel), ziprasidone(Drug information on ziprasidone) (Geodon), and even melatonin(Drug information on melatonin) at bedtime; all have shown some efficacy in the management of delirium, according to Dr. Booth-Jones, but not specifically in elderly patients. Dementia Dementia can occur in elderly cancer patients, either as a primary disease (perhaps premorbid to a cancer diagnosis) or secondary to cancer or its treatment. Some aspects of dementia are treatable using specific pharmacologic interventions, Dr. Booth- Jones said. Often the first step in treating dementia is use of cholinesterase inhibitors, including donepezil(Drug information on donepezil) (Aricept), galantamine(Drug information on galantamine) (Reminyl), and rivastigmine(Drug information on rivastigmine) (Exelon). The NMDA (Nmethyl- D-aspartate) receptor antagonist memantine(Drug information on memantine) has shown promise in Europe and has been distributed by the Frankfurt-based pharmaceutical company Merz in Germany and other parts of Europe since mid 2002, under the brand name Axura. In late September, an advisory committee to the US Food and Drug Administration (FDA) unanimously recommended that memantine be approved for moderate to severe Alzheimer's disease. On October 17, Forest Laboratoriesreceived approval from the FDA to develop and market memantine in the US, under the brand name Namenda; Forest expects the drug to be available in January 2004. Antihypertensives also may play a role in the treatment of dementia, Dr. Booth-Jones said, and investigations are underway into the possible preventive role of statins; vitamins; and anti-inflammatory drugs, including the selective cyclooxygenase-2 (COX- 2) inhibitors. Apathy Apathy can arise as a reaction to cancer or some aspect of cancer treatment affecting the central nervous system (eg, radiation). It is often treated with psychostimulants, including long-acting formulations of methylphenidate (D-methylphenidate [Focalin]). An ongoing phase III study is evaluating D-methylphenidate; in addition, use of modafinil(Drug information on modafinil) (Provigil) has increased "dramatically" as a potential treatment, said Dr. Booth-Jones. "We found that our patients who don't have much physical slowing but have a change in ability to stay focused over time benefit from Provigil," she said.