Abstract
Background: Antipsychotics are commonly used in the elderly to treat the behavioural symptoms of dementia. Randomized controlled trial data on the safety of antipsychotics are limited and little is known about the long-term effects of these medicines. Observational studies have investigated the risk of hip fracture and pneumonia associated with the use of antipsychotics, but varying results may be due to lack of control for unmeasured confounding.
Objective: The aim of the study was to investigate the risk of hospitalization for hip fracture and pneumonia in elderly subjects exposed to antipsychotic medication using the self-controlled case-series design to control for unmeasured confounding.
Methods: The source of data for this study was the Australian Government Department of Veterans’ Affairs Health Care Claims Database. A self-controlled case-series design was used to measure the excess risk of hospitalization for hip fracture and pneumonia after antipsychotic exposure compared with no-exposure over the 4-year period from 2005 to 2008.
Results: There was a significantly increased risk of hip fracture 1 week after exposure to typical antipsychotics, and the risk remained significantly raised with >12 weeks of continuous exposure (incidence rate ratio [IRR] 2.19; 95% CI 1.62, 2.95). The risk of hip fracture was highest in the first week after initiation of atypical antipsychotics (IRR 2.17; 95% CI 1.54, 3.06). The risk then declined with longer-term treatment; however, it remained significantly raised with >12 weeks of continuous exposure (IRR 1.43; 95% CI 1.23, 1.66). The risk of hospitalization for pneumonia was raised in all post-exposure periods for both typical and atypical antipsychotics.
Conclusions: Antipsychotic use in the elderly is associated with an increased risk of hospitalization for hip fracture and pneumonia. Given the increased risks of morbidity and mortality associated with these outcomes, practitioners should consider these additional risks when prescribing antipsychotics to treat behavioural symptoms of dementia in the elderly.
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References
Ballard C, Fossey J, Sharp S. Antipsychotics in patients with Alzheimer’s disease: what is their clinical value? Nat Clin Pract Neurol 2007; 3(5): 248–9
De Deyn PP, Katz IR, Brodaty H, et al. Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone. Clin Neurol Neurosurg 2005; 107(6): 497–508
Katz I, de Deyn PP, Mintzer J, et al. The efficacy and safety of risperidone in the treatment of psychosis of Alzheimer’s disease and mixed dementia: a meta-analysis of 4 placebo-controlled clinical trials. Int J Geriatr Psychiatry 2007; 22(5): 475–84
Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006; 14(3): 191–210
Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006; 355(15): 1525–38
Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev 2006; (1): CD003476
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: metaanalysis of randomized placebo-controlled trials. JAMA 2005; 294(15): 1934–43
Haupt M, Cruz-Jentoft A, Jeste D. Mortality in elderly dementia patients treated with risperidone. J Clin Psychopharmacol 2006; 26(6): 566–70
Normand SL, Sykora K, Li P, et al. Readers guide to critical appraisal of cohort studies: 3. Analytical strategies to reduce confounding. BMJ 2005; 330(7498): 1021–3
Liperoti R, Onder G, Lapane KL, et al. Conventional or atypical antipsychotics and the risk of femur fracture among elderly patients: results of a case-control study. J Clin Psychiatry 2007; 68(6): 929–34
Kolanowski A, Fick D, Waller JL, et al. Outcomes of antipsychotic drug use in community-dwelling elders with dementia. Arch Psychiatr Nurs 2006; 20(5): 217–25
Hugenholtz GW, Heerdink ER, van Staa TP, et al. Risk of hip/femur fractures in patients using antipsychotics. Bone 2005; 37(6): 864–70
Pouwels S, van Staa TP, Egberts AC, et al. Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study. Osteoporos Int 2009; 20: 1499–506
Cumming RG. Epidemiology of medication-related falls and fractures in the elderly. Drugs Aging 1998; 12(1): 43–53
Kishimoto T, Watanabe K, Shimada N, et al. Antipsychoticinduced hyperprolactinemia inhibits the hypothalamopituitary-gonadal axis and reduces bone mineral density in male patients with schizophrenia. J Clin Psychiatry 2008; 69(3): 385–91
Bostwick JR, Guthrie SK, Ellingrod VL. Antipsychoticinduced hyperprolactinemia. Pharmacotherapy 2009; 29(1): 64–73
Wada H, Nakajoh K, Satoh-Nakagawa T, et al. Risk factors of aspiration pneumonia in Alzheimer’s disease patients. Gerontology 2001; 47(5): 271–6
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(4): 661–6
Horwitz RI, Feinstein AR. The problem of “protopathic bias” in case-control studies. Am J Med 1980; 68(2): 255–8
Byrne GJ. Pharmacological treatment of behavioural problems in dementia. Aust Prescr 2005; 28: 67–70
Oldenbeuving AW, de Kort PL, Jansen BP, et al. Delirium in acute stroke: a review. Int J Stroke 2007; 2(4): 270–5
Kleijer BC, van Marum RJ, Egberts AC, et al. Risk of cerebrovascular events in elderly users of antipsychotics. J Psychopharmacol 2009; 23: 909–14
Whitaker HJ, Farrington CP, Spiessens B, et al. Tutorial in biostatistics: the self-controlled case series method. Stat Med 2006; 25(10): 1768–97
World Health Organization Collaborating Centre for Drug Statistics Methodology. Anatomical therapeutic chemical code classification index with defined daily doses [online]. Available from URL: http://www.whocc.no/atcddd/ [Accessed 2011 Apr 18]
Australian Government Department of Health and Ageing. Schedule of pharmaceutical benefits. PBS for health professionals [online]. Available from URL: http://www.pbs.gov.au/pbs/home [Accessed 2011 May 2]
National Centre for Classification in Health. The international statistical classification of diseases and related health problems, 10th revision, Australian modification (ICD-10-AM). 6th ed. National Centre for Classification in Health, Faculty of Health Sciences, University of Sydney, 2005
Whitaker HJ, Hocine MN, Farrington CP. The methodology of self-controlled case series studies. Stat Methods Med Res 2009; 18: 7–26
Wang PS, Bohn RL, Glynn RJ, et al. Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 2001; 158(6): 892–8
Hubbard R, Tattersfield A, Smith C, et al. Use of inhaled corticosteroids and the risk of fracture. Chest 2006; 130(4): 1082–8
Robertson BD, Robertson TJ. Postoperative delirium after hip fracture. J Bone Joint Surg Am 2006; 88(9): 2060–8
eTG Complete. West Melbourne (VIC): therapeutic guidelines, 2010 [online]. Available from URL: http://www.tg.org.au/index.php?sectionid=71 [Accessed 2001 May 2]
Gibson JE, Hubbard RB, Smith CJ, et al. Use of self-controlled analytical techniques to assess the association between use of prescription medications and the risk of motor vehicle crashes. Am J Epidemiol 2009; 169(6): 761–8
Hubbard R, Lewis S, Smith C, et al. Use of nicotine replacement therapy and the risk of acute myocardial infarction, stroke, and death. Tob Control 2005; 14(6): 416–21
Pratt NL, Roughead EE, Ramsay E, et al. Risk of hospitalisation for stroke associated with antipsychotic use in the elderly: self controlled case-series results. Drugs Aging. 2010; 27: 885–93
Farrington CP, Whitaker HJ. Semiparametric analysis of case series data. Appl Stat 2006; 55 (Pt 5): 553–94
Acknowledgements
The Veterans’ Medicines Advice and Therapeutics Education Service (MATES) project team and this study were supported by funding from the Australian Government, DVA, for the establishment of the Veterans’ MATES programme. The authors have no conflicts of interest to declare that are directly relevant to the content of this study.
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Pratt, N., Roughead, E.E., Ramsay, E. et al. Risk of Hospitalization for Hip Fracture and Pneumonia Associated with Antipsychotic Prescribing in the Elderly. Drug-Safety 34, 567–575 (2011). https://doi.org/10.2165/11588470-000000000-00000
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DOI: https://doi.org/10.2165/11588470-000000000-00000