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Management of agitation and aggression associated with Alzheimer disease

Abstract

Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms—atypical antipsychotics—have a modest but significant beneficial effect in the short-term treatment (over 6–12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics—preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

Key Points

  • Agitation and aggression are frequent and distressing symptoms that present major management problems in people with Alzheimer disease (AD)

  • Atypical antipsychotics are widely used in the pharmacological treatment of agitation and aggression, but their benefit is primarily limited to short-term management of aggression

  • Serious adverse events are associated with atypical antipsychotics in AD, including increased risk of stroke and death

  • An evidence base is emerging to support a variety of practical and easy-to-implement nonpharmacological treatments for the first-line treatment of agitation and aggression in AD

  • Further clinical trials of pharmacotherapy for agitation and aggression in AD are urgently needed, but preliminary data indicate that memantine, citalopram and carbamazepine could be promising alternatives to atypical antipsychotics

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Figure 1: Peak frequency of behavioral symptoms as Alzheimer disease progresses.

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We thank Cambridge Medical Communication Ltd for expert editorial assistance and Dr. Florinda Rosa for advice on content.

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Correspondence to Clive G. Ballard.

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C. G. Ballard has acted as a consultant for Arcadia, Esai, Lundbeck A/S, Novartis and Shire, has received honoraria from Esai, Lundbeck A/S, Novartis and Shire, and has received research support from Lundbeck A/S, Novartis, Shire and Wyeth. S. Gauthier has acted a consultant for and has received grants from Lundbeck and has acted as a consultant for Merz Pharmaceuticals. J. L. Cummings has acted as a consultant for and received honoraria from Forest, Lundbeck, Merz Pharmaceuticals, Pfizer, Janssen and Novartis and holds the copyright for the Neuropsychiatric Inventory (NPI). H. Brodaty has acted as a consultant for and received honoraria and grants from Lundbeck. G. T. Grossberg has acted as a consultant for Forest, Pfizer, Novartis, Medivation and PAM Labs and received grants from Elan and Wyeth. P. Robert has acted as a consultant for and received honoraria and grants from Lundbeck AIS, acted as a consultant for and received grants from Wyeth, received honoraria and grants from Esai Pharma, and received honoraria from Novartis and Janssen. C. G. Lyketsos has acted as a consultant for and received grants from Forest, Wyeth, Novartis and Lilly and has received grants from Pfizer.

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Ballard, C., Gauthier, S., Cummings, J. et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol 5, 245–255 (2009). https://doi.org/10.1038/nrneurol.2009.39

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