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Atypical Antipsychotic Drugs, Dementia, and Risk of DeathAtypical Antipsychotic Drugs, Dementia, and Risk of Death

JAMA. 2006;295(5):495-497. doi:10.1001/jama.295.5.495-b
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

ATYPICAL ANTIPSYCHOTIC DRUGS, DEMENTIA, AND RISK OF DEATH

To the Editor: In their meta-analysis, Dr Schneider and colleagues1 present evidence of a small but significant increase in the risk of death when antipsychotic drugs are used to treat neuropsychiatric symptoms in older adults with dementia. This risk develops quickly and is consistent across trials evaluating different antipsychotic agents. Antipsychotic drugs are used in a variety of treatment settings. For several reasons, the results of this meta-analysis may have implications for the safety of antipsychotic use in the setting of delirium treatment.

First, studies have linked delirium to an increased risk of mortality in older medical inpatients.2 The risk of death develops quickly. How delirium promotes premature mortality remains unknown. Although it has generally been assumed that the underlying delirium triggers death, studies of this association have not adjusted for exposure to antipsychotic drugs. This omission may be due in part to the underrecognition of the potentially lethal adverse effects of these drugs.

Second, antipsychotic drugs represent the most commonly recommended drug treatment for delirium.3 Unfortunately, there are few data from placebo-controlled trials to support their use in this context.4 In contrast, several large trials have examined the efficacy and safety of antipsychotic drugs to treat neuropsychiatric symptoms in dementia.1 As noted in the meta-analysis,1 it was only when 15 dementia trials involving 5204 participants were combined that the statistically significant effect on mortality was found.

Third, delirium and dementia share common features. Dementia is a major risk factor for delirium, and many elderly inpatients with delirium have an underlying dementia. The mean age of patients in many delirium studies is approximately 80 years,2 which is similar to the mean age observed in dementia trials.1 Antipsychotic drugs are used in both conditions in similar doses and for similar time periods.

The concerns that antipsychotic medications might heighten mortality among vulnerable older adults with dementia, and possibly also delirium, are compounded by the modest efficacy antipsychotic drugs typically demonstrated when used to treat these conditions. More research is needed to determine the risks and benefits of antipsychotic drugs in delirium. More effective and less toxic treatments for delirium are required. To date, the most effective strategy for delirium appears to be a nonpharmacological, multicomponent preventive approach.5 Efforts are needed to successfully incorporate such strategies into the routine care of older adults at risk of developing delirium.

Financial Disclosures: None reported.

References
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.  JAMA. 2005;2941934-1943
PubMed
Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up.  Arch Intern Med. 2005;1651657-1662
PubMed
American Psychiatric Association.  Practice guideline for the treatment of patients with delirium.  Am J Psychiatry. 1999;156(5 suppl)  1-20
PubMed
Cole MG, Primeau FJ, Elie M. Delirium: prevention, treatment, and outcome studies.  J Geriatr Psychiatry Neurol. 1998;11126-137
PubMed
Inouye SK, Bogardus ST, Charpentier PA.  et al.  A multicomponent intervention to prevent delirium in hospitalized older patients.  N Engl J Med. 1999;340669-676
PubMed

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Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.  JAMA. 2005;2941934-1943
PubMed
Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up.  Arch Intern Med. 2005;1651657-1662
PubMed
American Psychiatric Association.  Practice guideline for the treatment of patients with delirium.  Am J Psychiatry. 1999;156(5 suppl)  1-20
PubMed
Cole MG, Primeau FJ, Elie M. Delirium: prevention, treatment, and outcome studies.  J Geriatr Psychiatry Neurol. 1998;11126-137
PubMed
Inouye SK, Bogardus ST, Charpentier PA.  et al.  A multicomponent intervention to prevent delirium in hospitalized older patients.  N Engl J Med. 1999;340669-676
PubMed
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