Long-Term Antipsychotic Use and Major Cardiovascular Events: A Retrospective Cohort Study
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OBJECTIVE: Chronic treatment with antipsychotics may result in both metabolic side effects and cardiovascular disease. Our aim was to evaluate the effect of antipsychotic medications categorized by their metabolic side effect profiles as low, intermediate, or high risk on major cardiovascular events. METHODS: A retrospective cohort study was conducted in adult outpatients aged 30 years or older initiating antipsychotic treatment from 2002 to 2007. Antipsychotic medications were divided into 3 groups (low-, intermediate-, and high-risk) according to the severity of their side-effect profiles in developing metabolic abnormalities associated with cardiovascular disease. The primary outcome measure was the time to the composite of acute myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral artery disease, or a new revascularization procedure. Inverse probability weighting of a marginal structural Cox model was used to adjust for confounding. RESULTS: A total of 1,008 patients were included (mean age = 72.4 years, median follow-up = 36.5 months), and 19.6% of patients experienced the primary outcome. The adjusted hazard ratios of a major cardiovascular event for patients in the high- or intermediate-risk medication groups compared to the low-risk group were 2.82 (95% CI, 1.57-5.05) and 2.57 (95% CI, 1.43-4.63), respectively. CONCLUSIONS: Older adult patients under antipsychotic regimens with high or intermediate risk of metabolic side effects may face a higher incidence of major cardiovascular events than those under a low-risk regimen during long-term follow-up.
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In older adults, psychotropic use has been associated with risk of severe adverse effects such as falls, stroke and mortality.
“In older adults, psychotropic use has been associated with the risk of severe adverse effects such as falls [13–18], stroke [17, 19–22] and mortality [13, 23–25].”
From Stakeholders' views on the use of psychotropic medication in older people: a systematic review (2022) · cites this paper as [22]
The Clinical Points section associates antipsychotic treatment with higher all-cause mortality in older adults, and the Discussion reports an enhanced risk of stroke in the study population. The paper does not establish a risk of falls, and its findings concern antipsychotics rather than psychotropic drugs generally. (LLM, conf=0.86)
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References 21 · Cited by 24
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- Frayne SM, Halanych JH, Miller DR, et al. Disparities in diabetes care: impact of mental illness. Arch Intern Med. 2005;165(22):2631-2638.
- Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. 2007;64(10):1123-1131.
- Wooltorton E. Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials. CMAJ. 2004;170(9):1395. P u b M e d d o i : 1 0 . 1 5 0 3 / c m a j . 1 0 4 0 5 3 9
- P u b M e d 12. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry. 2004;65(2):267-272.
- You are prohibited from making this PDF publicly available. , @psychiatrist.2017 Copyright Physicians Postgraduate Press, Inc. It is illegal to post this copyrighted PDF on any website. e8 J Clin Psychiatry 78:0, Month 2017 Szmulewicz et al 25. Bodén R, Edman G, Reutfors J, et al. A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice. Neuropsychiatr Dis Treat. 2013;9:371-377.
- Newcomer JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007;68(suppl 4):8-13. P u b M e d 27. Tschoner A, Engl J, Laimer M, et al. Metabolic side effects of antipsychotic medication. Int J Clin Pract. 2007;61(8):1356-1370.
- Ventriglio A, Gentile A, Stella E, et al. Metabolic issues in patients affected by schizophrenia: clinical characteristics and medical management. Front Neurosci. 2015;9:297. P u b M e d d o i : 1 0 . 3 3 8 9 / f n i n s . 2 0 1 5 . 0 0 2 9 7
- Wimmer BC, Bell JS, Fastbom J, et al. Medication regimen complexity and polypharmacy as factors associated with all- cause mortality in older people: a population-based cohort study. Ann Pharmacother. 2016;50(2):89-95. P u b M e d d o i : 1 0 . 1 1 7 7 / 1 0 6 0 0 2 8 0 1 5 6 2 1 0 7 1
- Woods SW. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry. 2003;64(6):663-667.
- Huybrechts KF, Rothman KJ, Silliman RA, et al. Risk of death and hospital admission for major medical events after initiation of psychotropic medications in older adults admitted to nursing homes. CMAJ. 2011;183(7):E411-E419.
- Valeri L, VanderWeele TJ. SAS macro for causal mediation analysis with survival data. Epidemiology. 2015;26(2):e23-e24. P u b M e d d o i : 1 0 . 1 0 9 7 / E D E . 0 0 0 0 0 0 0 0 0 0 0 0 0 2 5 3
- VanderWeele TJ. Mediation analysis: a practitioner's guide. Annu Rev Public Health. 2016;37:17-32. P u b M e d d o i : 1 0 . 1 1 4 6 / a n n u r e v -p u b l h e a l t -0 3 1 5 -0 2 1 4 0 2
- Douglas IJ, Smeeth L. Exposure to antipsychotics and risk of stroke: self controlled case series study. BMJ. 2008;337:a1227. P u b M e d d o i : 1 0 . 1 1 3 6 / b m j . a 1 2 2 7
- Layton D, Harris S, Wilton LV, et al. Comparison of incidence rates of cerebrovascular accidents and transient ischaemic attacks in observational cohort studies of patients prescribed risperidone, quetiapine or olanzapine in general practice in England including patients with dementia. J Psychopharmacol. 2005;19(5):473-482. P u b M e d d o i : 1 0 . 1 1 7 7 / 0 2 6 9 8 8 1 1 0 5 0 5 6 5 2 4
- Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360(3):225-235.
- Trifirò G, Spina E, Gambassi G. Use of antipsychotics in elderly patients with dementia: do atypical and conventional agents have a similar safety profile? Pharmacol Res. 2009;59(1):1-12. P u b M e d d o i : 1 0 . 1 0 1 6 / j . p h r s . 2 0 0 8 . 0 9 . 0 1 7
- Wu C-S, Chang C-M, Tsai Y-T, et al. Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study. J Clin Psychiatry. 2015;76(9):1216-1223.
- Trollor JN, Chen X, Chitty K, et al. Comparison of neuroleptic malignant syndrome induced by first-and second-generation antipsychotics. Br J Psychiatry. 2012;201(1):52-56. P u b M e d d o i : 1 0 . 1 1 9 2 / b j p . b p . 1 1 1 . 1 0 5 1 8 9 Editor's Note: We encourage authors to submit papers for consideration as a part of our Early Career Psychiatrists section.
- Erika F. H. Saunders, MD, at esaunders@psychiatrist.com.
- Authors
- Szmulewicz, A. G., Angriman, F., Pedroso, F. E., Vazquez, C., & Martino, D. J.
- Affiliations
- Favaloro University (AR)
- Harvard University (US)
- NewYork–Presbyterian Hospital (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2017-10-25
- Volume
- 78
- Issue
- 8
- Pages
- e905-e912
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2606959399
- Cited by
- 24
- References
- 21
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 2 · 2017: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Keywords
- antipsychotic drugs, cardiovascular events, metabolic side effects, cardiovascular risk, myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral arterial disease, revascularization, older adults, long-term antipsychotic use
- MeSH terms
- Long Term Adverse Effects, Adult, Aged, Argentina, Mental Disorders, Cardiovascular Diseases, Delayed-Action Preparations, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Antipsychotic Agents, Incidence, Proportional Hazards Models, Risk Assessment
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