Behavior Disorders of Dementia: Recognition and Treatment

DementiaTABLE 1Pharmacologic Agents for Management of Psychotic Disorders of DementiaAgent Dosage range Outcome NotesAcetylcholinesterase inhibitorsDonepezil (Aricept) 10,11 10 mg at bedtime Improvement in outpatientsbut not in patients inextended-care facilitiesGalantamine (Razadyne:formerly Reminyl) 12Rivastigmine (Exelon) 136 to 12 mg twiceper day3 to 6 mg twiceper dayImprovement onNeuropsychiatric InventoryLess anxiety and psychosisSecondary data analysis in populationsstudied for cognitive lossSecondary endpoint in populationsstudied for cognitive lossSecondary endpoint in populationsstudied for cognitive lossAnticonvulsants and mood stabilizersCarbamazepineVariable May reduce aggression Side effects and toxicity limit use.(Tegretol) 14,15Divalproex(Depakote) 16,17375 to 1,375 mgper dayContinued improvementin agitation over time;well toleratedAntidepressantsCitalopram (Celexa) 18,19 10 to 40 mg per day Reduced agitation —Fluoxetine (Prozac) 20 5 to 40 mg per day — No data for effect in nondepressedpatientsSertraline (Zoloft) 20 25 to 200 mg per day — No data for effect in nondepressedpatientsTrazodone (Desyrel) 14,15 25 to 300 mg per day Reduced verbal aggression —AnxiolyticsBuspirone (BuSpar) 15 to 30 mg per day — No randomized clinical trials support use.Lorazepam (Ativan) 21 0.5 to 5 mg per day — No randomized clinical trials supportuse. Restrict use to patients with acuteagitation.Atypical antipsychoticsClozapine (Clozaril) 22,23 25 to 50 mg atbedtimeEffective in reducing druginducedpsychosis in patientswith Parkinson’s diseaseUse limited by required hematologicmonitoring.Olanzapine (Zyprexa) 24Quetiapine (Seroquel) 25Risperidone(Risperdal) 26,27Typical antipsychotics2.5 to 10 mg atbedtime12.5 to 300 mgat bedtime0.5 to 1.5 mg atbedtimeImprovement in agitation andaggressionResults in psychosis werenegative.Improvement in psychosisand agitationHaloperidol (Haldol) 28,29 < 1.5 mg per day Variably effective at lowdosagesFDA = U.S. Food and Drug Administration.Information from references 10 through 29.—Significant sedation when given athigher dosages; use with cautionin patients with diabetes.Antipsychotic of choice in patients withparkinsonian symptoms.FDA has warned about “cerebrovascularevents” in patients taking this drug.Side effects limit use; not recommendedexcept in patients with acute agitationand delirium.suggests no clear differences in clinical response. However,side effects (primarily prolonged rigidity) limitthe use of haloperidol. It is one of the few drugs notimplicated in the risk of falls in older adults, but thiseffect may be a result of marked impairment in patientmobility or its use in patients who are unresponsive toother agents. 36ANTICONVULSANTSAnticonvulsant agents typically are used when psychoticbehaviors result in aggressive behavior. Increasingevidence supports the use of divalproex (Depakote)or carbamazepine (Tegretol). These drugs are recommendedas second-line agents in patients with inadequateresponse to antipsychotic agents. Multiple small, relatively650 American Family Physician www.aafp.org/afp Volume 73, Number 4 February 15, 2006

Dementiashort-term trials 16,17 have proven anticonvulsants to beeffective and well-tolerated. In practice, however, sideeffects, drug interaction, and a narrow therapeutic windowmay limit the use of carbamazepine. Data suggestthat patients taking divalproex have continued symptomaticimprovement on a stable dosage over time, althoughthis effect may reflect the natural history of behavior disorders.Sedation is a common side effect of these agentsand may limit their use. Most of the data on gabapentin(Neurontin) has been anecdotal.ACETYLCHOLINESTERASE INHIBITORSAcetylcholinesterase inhibitors such as donepezil (Aricept),galantamine (Razadyne: formerly Reminyl), andrivastigmine (Exelon) have been associated with a reductionin problem behaviors in patients with dementia.However, these drugs should not be considered first-lineagents in the treatment of psychosis but rather adjunctivetreatment. Data on primary endpoints of cognitivefunction in patients taking acetylcholinesterase inhibitorsconsistently show a delay in time to institutionalization,which may reflect improved behavior, a delay in onset ofbehavior symptoms, or retention of function. Althoughthe responses are modest, even small gains or stabilizationof symptoms may lower the burden for patients andtheir caregivers.ANTIDEPRESSANTSThe distinction between depression with psychotic featuresand psychotic symptoms of dementia may be problematic,especially in patients with a history of depressionor prominent negative symptoms. Small series resultssuggest that the use of selective serotonin reuptakeinhibitors 18 and trazodone (Desyrel) 28 may be effectiveand could be considered in selected patients.ANXIOLYTICSBenzodiazepines should not be considered first-linetherapy for management of chronic behavior disordersof dementia, even in patients with prominent anxiety.However, community surveys show that these drugsare commonly used in these patients. 21 No publishedstudies support the routine use of benzodiazepines forthe management of psychotic symptoms of dementia.Chronic benzodiazepine use may worsen the behaviorabnormality because of the amnestic and disinhibitoryeffects of these drugs. In clinical practice, benzodiazepineuse should be limited to management of acute symptomsthat are unresponsive to redirection or other agents. 30A short-acting benzodiazepine with prompt sedativeeffects may be useful to empower the caregiver or nursingfacility during an episode of acute agitation that failsto respond to reassurance or removal of the precipitant.Short-acting benzodiazepines should be discontinued afterthe symptoms are controlled with other agents. Benzodiazepineswith short half-lives, no active metabolites, andlittle potential for drug interaction are recommended.In patients with intractable symptoms, hospitalizationin a geriatric psychiatry unit, if available, may be necessary.Patients with Lewy body disease, who often presentwith hallucinations, may be particularly resistant toneuroleptics and may worsen when treated with theseagents. Behavior problems are dynamic and variableand may resolve spontaneously. A reduction in dosage orelimination of agents is appropriate when target symptomsare improved. In long-term care settings, stepwisereduction in medication is more easily monitored andoften will be requested by the consulting pharmacist.Although the patient’s behavior may vary over time, nodata support the notion that tapering medications willlead to the emergence of uncontrollable symptoms.More research is needed on the pharmacologic managementof behavior problems and psychosis associated withdementia. Community-based clinical trials with a stepwise,multiple-agent design will provide a stronger basisfor recommendations and a better understanding of theimpact of pharmacologic interventions in these patients.Members of various family medicine departments develop articles for“Practical Therapeutics.” This article is one in a series coordinated bythe Department of Family and Geriatric Medicine at the University ofLouisville School of Medicine, Louisville, Ky. Guest editor of the series isJames G. O’Brien, M.D.The AuthorsABI V. RAYNER, M.D., M.P.H., is in private practice of geriatrics inMadisonville, Ky. She previously was assistant professor in the Departmentof Epidemiology and Clinical Investigative Sciences at the University ofLouisville (Ky.) School of Medicine. Dr. Rayner received her medical degreefrom the University of Florida College of Medicine, Gainesville, and completeda family medicine residency at the University of Wyoming School ofHuman Medicine in Casper. She received a master’s degree in public healthfrom Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.JAMES G. O’BRIEN, M.D., is the Margaret D. Smock Endowed Chairin Geriatrics and professor and chair of the Department of Family andGeriatric Medicine at the University of Louisville School of Medicine. Dr.O’Brien received his medical degree from University College Faculty ofMedicine, Dublin, Ireland, and completed a family practice residency atSaginaw (Mich.) Cooperative Hospitals and a fellowship in geriatrics atDuke University Medical Center, Durham, N.C.BEN SCHOENBACHLER, M.D., is assistant professor of psychiatry andbehavioral sciences and director of the memory disorders program at theUniversity of Louisville School of Medicine. Dr. Schoenbachler receivedhis medical degree from the University of Kentucky College of Medicine,Lexington, and completed a combined residency in neurology and psychiatryat Tulane University School of Medicine, New Orleans, La.February 15, 2006 Volume 73, Number 4 www.aafp.org/afp American Family Physician 651

DementiaAddress correspondence to Abi V. Rayner, M.D., M.P.H., 444 S. MainSt., Madisonville, KY 42431 (e-mail: doctor@rayner.net). Reprints arenot available from the authors.Author disclosure: Nothing to disclose.REFERENCES1. Holtzer R, Tang MX, Devanand DP, Albert SM, Wegesin DJ, Marder K,et al. Psychopathological features in Alzheimer’s disease: course andrelationship with cognitive status. J Am Geriatr Soc 2003;51:953-60.2. Leroi I, Voulgari A, Breitner JC, Lyketsos CG. The epidemiology of psychosisin dementia. Am J Geriatr Psychiatry 2003;11:83-91.3. Drevets WC, Rubin EH. Psychotic symptoms and the longitudinal courseof senile dementia of the Alzheimer type. Biol Psychiatry 1989;25:39-48.4. O’Donnell M, Molloy DW, Rabheru K. Dysfunctional behaviour in dementia:a clinician’s guide. Dundas, Ontario: New Grange Press; 2001.5. Small GW, Rabins PV, Barry PP, Buckholtz NS, DeKosky ST, Ferris SH, etal. 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Breier A, Meehan K, Birkett M, David S, Ferchland I, Sutton V, et al.A double-blind, placebo-controlled dose-response comparison ofintramuscular olanzapine and haloperidol in the treatment of acuteagitation in schizophrenia. Arch Gen Psychiatry 2002;59:441-8.35. Schneider LS, Pollock VE, Lyness SA. A metaanalysis of controlled trials ofneuroleptic treatment in dementia. J Am Geriatr Soc 1990;38:553-63.36. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people:a systematic review and meta-analysis: I. Psychotropic drugs. J AmGeriatr Soc 1999;47:30-9.652 American Family Physician www.aafp.org/afp Volume 73, Number 4 February 15, 2006