Delirium, Dementia, Apathy Require Individualized Treatment

December 1, 2003

This special supplement to Oncology News International presents 17 reports fromthe first annual Geriatric Oncology Consortium (GOC) multidisciplinary conference,‘‘Advancing Cancer Care in the Elderly.’’ Reports focus on issues in geriatric oncology,in particular team-based patient assessment and care delivery,adherence to medication, accrual to clinical trials, appropriate dosingthrough supportive therapy, radiation therapy, cognition problems, pain management,reassessment of outcomes, and caregiving issues.

WASHINGTON, DC-Comorbidneuropsychiatric conditionsin elderly cancer patients, which commonlyoccur but are underdiagnosed,should be identified and treated toimprove quality of life, according toclinical psychologist Margaret Booth-Jones, PhD.Reporting at the first annual GeriatricOncology Consortium multidisciplinaryconference, entitled "AdvancingCancer Care in the Elderly,"Dr. Booth-Jones said delirium, dementia,and apathy are just several neuropsychiatricchanges that can impactthe patient's personality, sense of self,and independence."Anything that does this is a realthreat to who we are, and dramaticallyaffects quality of life, not only for theelderly patient, but for family membersand loved ones," said Dr. Booth-Jones, assistant professor of psychosocialand palliative care, H. Lee MoffittCancer Center, Tampa, Florida.Treatment needs to be individualized,she said, based not only on thecause of the neuropsychiatric condition,but also on the basis of eachelderly patient's symptoms, organfunction, and other medical comorbidities.Treatment must be reassessedfrequently-as often as once weekly-and modified as required untilthe patient receives optimal benefit.DeliriumDetermining the etiology of theneuropsychiatric disorder may requirea careful patient assessment. Delirium,for example, can have a numberof causes, including drug intoxicationor withdrawal, sleep deprivation, cardiovasculardisease, or an underlyingmetabolic disorder.Delirium in the elderly is usually ofsudden onset, and it may be misiden-tified as dementia or depression. Inaddition to typical symptoms such asdisorientation, consciousness disturbance,and waxing/waning alertness,the elderly patient may become paranoid."This can be very stressful forthe caregiver or family," Dr. Booth-Jones said.Delirium often can be managednonpharmacologically using interventionprotocols that target specific riskfactors for the neuropsychiatric condition.For example, clinicians can targetsleep deprivation with protocolsthat encourage or enhance rest, whilecognitive impairment can be addressedwith protocols that emphasize orien-tation or therapeutic activities (AnnIntern Med 135:32-40, 2001).Multiple pharmacologic treatmentshave been tried in delirium. In onedouble-blind trial of hospitalized AIDSpatients, investigators found that lowdoses of neuroleptics (chlorpromazineand haloperidol [Haldol]) were effectiveand produced few adverse events.On the other hand, a benzodiazepine(lorazepam) was not effective and producedenough treatment-limiting sideeffects that investigators terminatedthat arm of the study (Am J Psychiatry153:231-237, 1996).In an open trial, although olanzapine(Zyprexa) was determined to be"clinically efficacious and safe" fortreating delirium in hospitalized medicallyill patients, age greater than 70years was a factor associated with pooreroutcome (Psychosomatics 43:175-182, 2002).Other drugs tried for delirium includemethylphenidate (Concerta,Methylin, Ritalin), droperidol (Inapsine),quetiapine (Seroquel), ziprasidone(Geodon), and even melatoninat bedtime; all have shown some efficacyin the management of delirium,according to Dr. Booth-Jones, but notspecifically in elderly patients.DementiaDementia can occur in elderly cancerpatients, either as a primary disease(perhaps premorbid to a cancerdiagnosis) or secondary to cancer orits treatment. Some aspects of dementiaare treatable using specific pharmacologicinterventions, Dr. Booth-Jones said.Often the first step in treating dementiais use of cholinesterase inhibitors,including donepezil (Aricept),galantamine (Reminyl), and rivastigmine(Exelon). The NMDA (Nmethyl-D-aspartate) receptor antagonistmemantine has shown promisein Europe and has been distributed bythe Frankfurt-based pharmaceuticalcompany Merz in Germany and otherparts of Europe since mid 2002, underthe brand name Axura. In late September,an advisory committee to theUS Food and Drug Administration(FDA) unanimously recommendedthat memantine be approved for moderateto severe Alzheimer's disease.On October 17, Forest Laboratoriesreceived approval from the FDA todevelop and market memantine in theUS, under the brand name Namenda;Forest expects the drug to be availablein January 2004.Antihypertensives also may play arole in the treatment of dementia, Dr.Booth-Jones said, and investigationsare underway into the possible preventiverole of statins; vitamins; andanti-inflammatory drugs, includingthe selective cyclooxygenase-2 (COX-2) inhibitors.ApathyApathy can arise as a reaction tocancer or some aspect of cancer treatmentaffecting the central nervous system(eg, radiation). It is often treatedwith psychostimulants, includinglong-acting formulations of methylphenidate(D-methylphenidate [Focalin]).An ongoing phase III study isevaluating D-methylphenidate; in addition,use of modafinil (Provigil) hasincreased "dramatically" as a potentialtreatment, said Dr. Booth-Jones."We found that our patients whodon't have much physical slowing buthave a change in ability to stay focusedover time benefit from Provigil," shesaid.