Psychiatry - July 2008 - (Page 30)

[trend watch] that these agents have been associated with an increased risk of mortality in the elderly. The label asserts the following: Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of 17 placebocontrolled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5 percent, compared to a rate of about 2.6 percent in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Note that the exposures were for 10 weeks and it is uncertain from the available data if more deaths are to be expected with longer exposures or if patients at risk express their vulnerabilities early and succumb soon after exposure. The absolute risk remains small (4.5% compared to the placebo rate of 2.6%) but the relative risk— an almost two-fold increase—is not trivial. Also uncertain from the available data is the mechanism by which mortality is exacerbated, although even mild drug-induced parkinsonism with attendant immobility and swallowing difficulties may contribute to the elevated rates of pneumonia reported among elderly patients receiving atypical agents.1 Not all analyses of the data have supported the conclusions drawn by the FDA, but an analysis by Schneider, et al.,2 came to nearly identical conclusions. 30 Psychiatry 2008 [ J U L Y ] Although the mortality warning is mandated only for atypical antipsychotics, similar increases in death rates have been identified among dementia patients treated with conventional neuroleptic agents.3,4 The warning on atypicals and the concern over conventional neuroleptics has created tremendous uncertainty in the prescribing community. The safety concerns are heightened by recent studies raising serious questions about the effectiveness of these agents as currently used in clinical practice. They are often given in doses that are too low for periods of time that are too short to draw therapeutic conclusions, thus possibly exposing patients to the risks while not providing the putative benefits of these agents.5 There are no therapies approved by the FDA for treatment of behavioral disturbances in dementia, and alternative medications, such as moodstabilizing anticonvulsants, have lacked efficacy in recent randomized, controlled trials.6,7 Antidementia drugs, such as memantine, may have anti-agitation effects,8 but many patients develop treatment-requiring behavioral syndromes despite treatment with these drugs. Thus, clinicians are faced with the dilemma that the most common behavioral disturbance in dementia for which medications are needed has no satisfactory treatment. Antipsychotics are used because they have been shown in some trials to be efficacious and because the clinician has few if any viable options.9–11 Not treating psychosis and agitation in dementia patients may also have consequences: injury to patient and spouse, premature institutionalization, and use of restraints, among others. Thus, the decision to use these agents must be based on a dialogue between informed caregivers and patients and their physicians with candid discussions of data regarding efficacy and risks. A ban on use of these agents would be as inappropriate as their intemperate use. Figures 1 and 2 demonstrate that this is the course adopted by most current practitioners. The American College of Neuropsychopharmacology Work Group and a recent Best Practices Panel endorsed this approach in recent guidelines for use of atypicals in patients with dementia.12,13 The current situation is untenable. The rising number of elderly and the concomitant anticipated dramatic rise in the number of patients with dementia makes a marked increase in the number of elderly cognitively impaired persons requiring treatment for behavioral disturbances inevitable. Progress in understanding the neurobiology of Alzheimer’s disease and enhanced understanding of the neurobiology of psychosis may lead to discovery of agents with psychotropic properties and safety profiles superior to those currently available.14 REFERENCES 1. Knol W, van Marum RJ, Jansen PA, et al. Antipsychotic drug use and risk of pneumonia in elderly people. J Am Geriatr Soc. 2008;56:661–666. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: metaanalysis of randomized placebocontrolled trials. JAMA. 2005;294:1934–1943. Kales HC, Valenstein M, Kim HM, 2. 3. 30

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Psychiatry - July 2008 Editor's Message Editorial Advisory Board Contents PsychRx Letters to the Editor Reliability of Diagnoses: Do Psychiatrists Use Structured Interviews In Real Clinical Settings? Trend Watch: Use of Atypical Antipsychotics in the Elderly Review: The Struggle for Mental Healthcare in New Orleans-One Case at a Time Psychotherapy Rounds: Psychotherapeutic and Adjuntive Pharmacologic Approaches to Treating Posttraumatic Stress Disorder Original Research: Baseline Dissociation and Prospective Success in Special Forces Assessment and Selection Commentary: Performance-Enhancing Drugs: Where Should the Line Be Drawn and By Whom? Commentary: Psychiatric Diagnosis and the Pathlogist's View of Schizophrenia Journal Watch Classified Advertising Information for Authors

Psychiatry - July 2008

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