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Antipsychotic Medications and the Elderly

Effects on Cognition and Implications for Use

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Abstract

Despite being frequently prescribed in the elderly, antipsychotic medications are commonly associated with adverse effects in this population, including sedative, orthostatic and extrapyramidal adverse effects. Growing evidence suggests that antipsychotics can also cause deleterious cognitive effects in some elderly patients. Preclinical and growing clinical evidence indicates that inhibitory effects on dopaminergic, cholinergic and histaminergic neurochemical systems may account for antipsychotic-associated cognitive impairment in the elderly.

A review of published reports of the cognitive effects of antipsychotics in the elderly suggests that newer antipsychotic medications may possess a more favourable cognitive profile than that of traditional agents in this population. The cognitive effect that a specific antipsychotic will have in the elderly, however, is likely better predicted by considering the pharmacodynamic action of an individual agent in combination with the pathophysiology of the condition being treated. Agents with relatively weak dopamine inhibiting effects (e.g. clozapine and quetiapine), for example, would theoretically have a cognitive profile superior to that of agents with higher degrees of dopaminergic inhibition (all traditional agents, risperidone, olanzapine and ziprasidone) when used for conditions associated with diminished dopamine function (e.g. idiopathic Parkinson’s disease). Drugs with weak anticholinergic effects (high-potency traditional agents, risperidone, quetiapine and ziprasidone) would theoretically be less likely to cause cognitive impairment than agents with high degrees of cholinergic receptor blocking actions (clozapine and olanzapine) when treating patients with impaired cholinergic function (e.g. Alzheimer’s disease). Cholinergic agonist effects of clozapine and olanzapine may, however, mitigate potential adverse cognitive effects associated with the cholinergic blocking actions of these agents.

Large, rigorous trials comparing the cognitive effects of antipsychotics with diverse pharmacodynamic actions are lacking in the elderly and are needed.

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Acknowledgements

The authors sincerely thank Bryan Elwood for his assistance in manuscript preparation.

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Authors and Affiliations

  1. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA

    Matthew J. Byerly, Mary T. Weber & Emmeline Lescouflair

  2. Department of Psychiatry, University of Arkansas for Medical Sciences and the Little Rock Veterans Administration Medical Center, Little Rock, Arkansas, USA

    Deean L. Brooks, Lisa R. Snow & Mark A. Worley

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  1. Matthew J. Byerly
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Correspondence to Matthew J. Byerly.

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Byerly, M.J., Weber, M.T., Brooks, D.L. et al. Antipsychotic Medications and the Elderly. Drugs & Aging 18, 45–61 (2001). https://doi.org/10.2165/00002512-200118010-00004

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