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Study Findings Hard to Interpret

Study Findings Hard to Interpret Given the growing prevalence of dementia, it is essential to assess the adverse effects of common treatments for behavioral problems. We welcome the study by Pariente et al1 addressing the role of antipsychotic agents (APs) in causing myocardial infarction. However, there are several issues that warrant more attention. Our main concern is the possible bias in the selection of persons using APs because of behavioral problems. These problems may be related to myocardial infarction and unfavorable medications. Baseline characteristics show that people using APs had by far more antidepressant and anxiolytic medications. Second, as the authors state themselves, it is important to distinguish between the different classes of APs, since, for instance, atypical APs are known to increase the risk of (vascular-related) death and may do so through different pathways.2 Third, external validity may be a problem. The study sample was selected from patients with a cholinesterase inhibitor prescription. Tolerance to these drugs is limited to only 30% to 50% of initial users.3 Fourth, a limitation common to studies based on claims databases is that we only know whether certain drugs were dispensed, but not to what extent they were actually taken. Prescribed duration may thus differ from actual exposure. Medication adherence in community-dwelling patients with dementia is far from optimal.4 Fifth, there is a general lack of clarity about the theoretical underpinnings of such a relationship. Recent studies have suggested a common genetic basis for Alzheimer disease and myocardial infarction.5 Atypical APs work on several neurotransmitters, such as serotonin, which may also have effects on blood vessels. More work on unraveling the mechanisms is definitely needed. Finally, the authors report that they included dementia severity as a covariate in their analysis, but it is unclear how severity was operationalized. All these issues jeopardize the interpretability of the study findings. We look forward to the authors' response. Back to top Article Information Correspondence: Dr van der Wouden, Department of General Practice and Elderly Health Care, EMGO Institute of Health and Care Research, VU University Medical Center Amsterdam, PO Box 7057, Room D-543, 1007 MB Amsterdam, the Netherlands (j.vanderwouden@vumc.nl). Financial Disclosure: None reported. References 1. Pariente A, Fourrier-Réglat A, Ducruet T, et al. Antipsychotic use and myocardial infarction in older patients with treated dementia. Arch Intern Med. 2012;172(8):648-65322450214PubMedGoogle ScholarCrossref 2. Gisev N, Hartikainen S, Chen TF, Korhonen M, Bell JS. Effect of comorbidity on the risk of death associated with antipsychotic use among community-dwelling older adults. Int Psychogeriatr. 2012;24(7):1058-106422364618PubMedGoogle Scholar 3. van den Bussche H, Kaduszkiewicz H, Koller D, et al. Antidementia drug prescription sources and patterns after the diagnosis of dementia in Germany: results of a claims data-based 1-year follow-up. Int Clin Psychopharmacol. 2011;26(4):225-23121394033PubMedGoogle Scholar 4. Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry. 2003;11(2):131-14512611743PubMedGoogle Scholar 5. Licastro F, Chiappelli M, Caldarera CM, et al. Sharing pathogenetic mechanisms between acute myocardial infarction and Alzheimer's disease as shown by partially overlapping of gene variant profiles. J Alzheimers Dis. 2011;23(3):421-43121098980PubMedGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2012.3764
Publisher site
See Article on Publisher Site

Abstract

Given the growing prevalence of dementia, it is essential to assess the adverse effects of common treatments for behavioral problems. We welcome the study by Pariente et al1 addressing the role of antipsychotic agents (APs) in causing myocardial infarction. However, there are several issues that warrant more attention. Our main concern is the possible bias in the selection of persons using APs because of behavioral problems. These problems may be related to myocardial infarction and unfavorable medications. Baseline characteristics show that people using APs had by far more antidepressant and anxiolytic medications. Second, as the authors state themselves, it is important to distinguish between the different classes of APs, since, for instance, atypical APs are known to increase the risk of (vascular-related) death and may do so through different pathways.2 Third, external validity may be a problem. The study sample was selected from patients with a cholinesterase inhibitor prescription. Tolerance to these drugs is limited to only 30% to 50% of initial users.3 Fourth, a limitation common to studies based on claims databases is that we only know whether certain drugs were dispensed, but not to what extent they were actually taken. Prescribed duration may thus differ from actual exposure. Medication adherence in community-dwelling patients with dementia is far from optimal.4 Fifth, there is a general lack of clarity about the theoretical underpinnings of such a relationship. Recent studies have suggested a common genetic basis for Alzheimer disease and myocardial infarction.5 Atypical APs work on several neurotransmitters, such as serotonin, which may also have effects on blood vessels. More work on unraveling the mechanisms is definitely needed. Finally, the authors report that they included dementia severity as a covariate in their analysis, but it is unclear how severity was operationalized. All these issues jeopardize the interpretability of the study findings. We look forward to the authors' response. Back to top Article Information Correspondence: Dr van der Wouden, Department of General Practice and Elderly Health Care, EMGO Institute of Health and Care Research, VU University Medical Center Amsterdam, PO Box 7057, Room D-543, 1007 MB Amsterdam, the Netherlands (j.vanderwouden@vumc.nl). Financial Disclosure: None reported. References 1. Pariente A, Fourrier-Réglat A, Ducruet T, et al. Antipsychotic use and myocardial infarction in older patients with treated dementia. Arch Intern Med. 2012;172(8):648-65322450214PubMedGoogle ScholarCrossref 2. Gisev N, Hartikainen S, Chen TF, Korhonen M, Bell JS. Effect of comorbidity on the risk of death associated with antipsychotic use among community-dwelling older adults. Int Psychogeriatr. 2012;24(7):1058-106422364618PubMedGoogle Scholar 3. van den Bussche H, Kaduszkiewicz H, Koller D, et al. Antidementia drug prescription sources and patterns after the diagnosis of dementia in Germany: results of a claims data-based 1-year follow-up. Int Clin Psychopharmacol. 2011;26(4):225-23121394033PubMedGoogle Scholar 4. Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry. 2003;11(2):131-14512611743PubMedGoogle Scholar 5. Licastro F, Chiappelli M, Caldarera CM, et al. Sharing pathogenetic mechanisms between acute myocardial infarction and Alzheimer's disease as shown by partially overlapping of gene variant profiles. J Alzheimers Dis. 2011;23(3):421-43121098980PubMedGoogle Scholar

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Oct 8, 2012

Keywords: myocardial infarction,dementia,polyendocrinopathies, autoimmune,behavioral problems

References