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Antipsychotic treatment effects on cardiovascular, cancer, infection, and intentional self-harm as cause of death in patients with Alzheimer's dementia

Published online by Cambridge University Press:  23 March 2020

R.-E. Nielsen ,
A. Lolk ,
M. Rodrigo-Domingo ,
J.-B. Valentin  and
K. Andersen
R.-E. Nielsen*
Affiliation:
Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Mølleparkvej 10, 9000Aalborg, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
A. Lolk
Affiliation:
Institute of Clinical Health, University of Southern Denmark, Department of Psychiatry, Odense, Region of Southern Denmark, Denmark
M. Rodrigo-Domingo
Affiliation:
Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Mølleparkvej 10, 9000Aalborg, Denmark
J.-B. Valentin
Affiliation:
Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Mølleparkvej 10, 9000Aalborg, Denmark
K. Andersen
Affiliation:
Institute of Clinical Health, University of Southern Denmark, Department of Psychiatry, Odense, Region of Southern Denmark, Denmark
*
*Corresponding author. Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Mølleparkvej 10, 9000 Aalborg, Denmark. E-mail address:ren@rn.dk (R.-E. Nielsen).
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Abstract

Background

Alzheimer's disease (AD), the most common disease causing dementia, is linked to increased mortality. However, the effect of antipsychotic use on specific causes of mortality has not yet been investigated thoroughly.

Methods

Utilizing the Danish nationwide registers, we defined a cohort of patients diagnosed with AD. Utilizing separate Cox regressions for specific causes of mortality, we investigated the effects of cumulative antipsychotic dosage after diagnosis and current antipsychotic exposure in the time period 2000–2011.

Results

In total, 45,894 patients were followed for 3,803,996 person-years. A total of 6129 cardiovascular related deaths, 2088 cancer related deaths, 1620 infection related deaths, and 28 intentional self-harm related deaths are presented. Current antipsychotic exposure increased mortality rate with HR between 1.92 and 2.31 for cardiovascular, cancer, and infection related death. Cumulative antipsychotic dosages were most commonly associated with increased rates of mortality for cardiovascular and infection as cause of death, whereas the associations were less clear with cancer and intentional self-harm as cause of death.

Conclusions

We showed that cumulative antipsychotic drug dosages increased mortality rates for cardiovascular and infection as cause of death. These findings highlight the need for further investigations of long-term effects of treatment and of possible sub-groups who could benefit from treatment.

Keywords

DementiaPsychopharmacologyMortalityEpidemiology
Type
Original article
Information
European Psychiatry , Volume 42 , May 2017 , pp. 14 - 23
Copyright
Copyright © European Psychiatric Association 2017

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References

Brodaty, H., Seeher, K., Gibson, L.Dementia time to death: a systematic literature review on survival time and years of life lost in people with dementia. Int Psychogeriatr 2012;24(7):1034–1045.CrossRefGoogle ScholarPubMed
Magaki, S., Yong, W.H., Khanlou, N., Tung, S., Vinters, H.V.Comorbidity in dementia: update of an ongoing autopsy study. J Am Geriatr Soc 2014;62(9):1722–1728.CrossRefGoogle ScholarPubMed
Brunnstrom, H.R., Englund, E.M.Cause of death in patients with dementia disorders. Eur J Neurol 2009;16(4):488–492.CrossRefGoogle ScholarPubMed
Romero, J.P., Benito-Leon, J., Louis, E.D., Bermejo-Pareja, F.Alzheimer's disease is associated with decreased risk of cancer-specific mortality: a prospective study (NEDICES). J Alzheimers Dis 2014;40(2):465–473.CrossRefGoogle Scholar
Erlangsen, A., Zarit, S.H., Conwell, Y.Hospital-diagnosed dementia and suicide: a longitudinal study using prospective, nationwide register data. Am J Geriatr Psychiatry 2008;16(3):220–228.CrossRefGoogle ScholarPubMed
Draper, B., Brodaty, H., Low, L.F., Richards, V.Prediction of mortality in nursing home residents: impact of passive self-harm behaviors. Int Psychogeriatr 2003;15(2):187–196.CrossRefGoogle ScholarPubMed
Schneider, L.S., Dagerman, K.S., Insel, P.Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294(15):1934–1943.CrossRefGoogle ScholarPubMed
Corbett, A., Burns, A., Ballard, C.Don’t use antipsychotics routinely to treat agitation and aggression in people with dementia. BMJ 2014;349:g6420.CrossRefGoogle ScholarPubMed
Ma, H., Huang, Y., Cong, Z., Wang, Y., Jiang, W., Gao, S.et al.The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimers Dis 2014;42(3):915–937.CrossRefGoogle ScholarPubMed
Nielsen, R.E., Lolk, A., Valentin, J.B., Andersen, K.Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with alzheimer's dementia. Acta Psychiatr Scand 2016;134(4):314–320. http://dx.doi.org/10.1111/acps.12614 [Epub 2016 Jun 30].CrossRefGoogle ScholarPubMed
Maust, D.T., Kim, H.M., Seyfried, L.S., Chiang, C., Kavanagh, J., Schneider, L.S.et al.Antipsychotics, other psychotropics and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry 2015;72(5):438–445.CrossRefGoogle ScholarPubMed
Jeste, D.V., Blazer, D., Casey, D., Meeks, T., Salzman, C., Schneider, L.et al.ACNP white paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33(5):957–970.CrossRefGoogle ScholarPubMed
Ballard, C., Hanney, M.L., Theodoulou, M., Douglas, S., McShane, R., Kossakowski, K.et al.The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 2009;8(2):151–157.CrossRefGoogle ScholarPubMed
Wang, P.S., Walker, A.M., Tsuang, M.T., Orav, E.J., Glynn, R.J., Levin, R.et al.Dopamine antagonists and the development of breast cancer. Arch Gen Psychiatry 2002;12(59):1147–1154. [0003-990; 12]CrossRefGoogle Scholar
Fond, G., Macgregor, A., Attal, J., Larue, A., Brittner, M., Ducasse, D.et al.Antipsychotic drugs: pro-cancer or anti-cancer? A systematic review. Med Hypotheses 2012;79(1):38–42.CrossRefGoogle ScholarPubMed
Emul, M., Kalelioglu, T.Etiology of cardiovascular disease in patients with schizophrenia: current perspectives. Neuropsychiatr Dis Treat 2015;11:2493–2503.CrossRefGoogle ScholarPubMed
Stahl, S.M., Mignon, L., Meyer, J.M.Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand 2009 03;119(3):171–179.CrossRefGoogle ScholarPubMed
Nielsen, R.E., Nielsen, J.Antipsychotic drug treatment for patients with schizophrenia. Clin Med Therap 2009;1:1053–1068.Google Scholar
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(1):CD003476.Google Scholar
Tiihonen, J., Lonnqvist, J., Wahlbeck, K., Klaukka, T., Niskanen, L., Tanskanen, A.et al.11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2016;620–627 [08/22;374(1474–547); 9690].Google Scholar
Kessing, L.V., Gerds, T.A., Feldt-Rasmussen, B., Andersen, P.K., Licht, R.W.Use of lithium and anticonvulsants and the rate of chronic kidney disease: a nationwide population-based study. JAMA Psychiatry 2015;4:1–10.Google Scholar
Vilalta-Franch, J., Lopez-Pousa, S., Calvo-Perxas, L., Garre-Olmo, J.Psychosis of alzheimer disease: prevalence, incidence, persistence, risk factors, and mortality. Am J Geriatr Psychiatry 2013;21(11):1135–1143.CrossRefGoogle ScholarPubMed
Garcez, M.L., Falchetti, A.C., Mina, F., Budni, J.Alzheimer s disease associated with psychiatric comorbidities. An Acad Bras Cienc 2015;87(Suppl. 2):1461–1473.CrossRefGoogle Scholar
Larson, E.B., Shadlen, M.F., Wang, L., McCormick, W.C., Bowen, J.D., Teri, L.et al.Survival after initial diagnosis of alzheimer disease. Ann Intern Med 2004;140(7):501–509.CrossRefGoogle ScholarPubMed
Nielsen, R.E., Uggerby, A.S., Jensen, S.O., McGrath, J.J.Increasing mortality gap for patients diagnosed with schizophrenia over the last three decades: a Danish nationwide study from 1980 to 2010. Schizophr Res 2013;146(1–3):22–27.CrossRefGoogle ScholarPubMed
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