Bipolar Disorder, Schizophrenia, and Uptake of Oral Anticoagulation Therapy in Patients With Atrial Fibrillation | Atrial Fibrillation | JAMA Network Open | JAMA Network
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Invited Commentary
May 17, 2021

Bipolar Disorder, Schizophrenia, and Uptake of Oral Anticoagulation Therapy in Patients With Atrial Fibrillation

Author Affiliations
  • 1Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway
  • 2Section for Epidemiology and Social Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
JAMA Netw Open. 2021;4(5):e2110116. doi:10.1001/jamanetworkopen.2021.10116

Patients with severe mental illnesses, such as schizophrenia and bipolar disorder, live 15 to 20 fewer years than the general population.1 This reduced lifespan is partly due to an increase in the relative risk of suicide or accidents, but most years of life are lost to somatic disorders, with cardiovascular diseases playing a major role in reducing life expectancy of both men and women with severe mental illness. Fenger-Grøn et al2 evaluate the use of oral anticoagulation therapy (OAT) in patients with bipolar disorder or schizophrenia who develop atrial fibrillation (AF). The aim of this extensive study was to explore whether bipolar disorder or schizophrenia is associated with a lower likelihood of OAT initiation among individuals with incident AF and lower OAT prevalence among those with prevalent AF. The study was a dynamic cohort covering all hospital-registered patients with AF discharged during 2005-2016 in Denmark, including both incident (n = 147 810) and prevalent (n = 199 219) cases with risk status defined by a CHA2DS2VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) risk score greater than or equal to 2. The data were obtained from the Danish Patient Register, Danish National Prescription Registry, and Danish Civil Registry System using the unique Danish national identity number, ensuring both quality and completeness.

The exposure variables were bipolar disorder and schizophrenia (or schizoaffective disorder) diagnosed in a general or psychiatric hospital, and outcomes were initiation and prevalence of OAT with use of vitamin K antagonists or novel oral anticoagulants (NOACs), but the patients were classified according to their latest prescription.2 The authors found that both bipolar disorder and schizophrenia were associated with lower frequency of OAT initiation after an incident AF diagnosis (bipolar disorder, −12.7% and schizophrenia, −24.5%) as well as lower use of OAT in patients with prevalent AF (bipolar disorder, −11.6% and schizophrenia, −21.6%). The associations were attenuated when adjusting for socioeconomic factors and comorbid conditions, especially for patients with bipolar disorder, but schizophrenia continued to be associated with a 15.5% lower rate of OAT initiation and 12.8% lower OAT prevalence.

The Danish study was based on hospitalized patients with AF, which represents the most seriously affected patients, and the study underestimates the total burden of this disorder in the population. It is unlikely, however, that patients with AF who have mental comorbidities treated at outpatient clinics should be receiving OAT to an extent that the observed associations should be biased.

The authors suggested that the most likely explanation for the worse outcome of cardiovascular disease in patients with severe mental illness is a lower likelihood of receiving preventive or curative treatment, in particular, with regard to individuals with schizophrenia.2 This treatment deficit can be due either to poorer treatment adherence or to inequity in prescribing and health care. The rather constant OAT deficit in prevalent cases over time is an argument against lack of adherence, suggesting that inequity and health disparity are the most important contributors to the lower treatment initiation. Disparity in OAT for patients with AF and mental comorbidity corresponds to the lower rate of cardiovascular invasive procedures, as well as disparities in treatment for cancer in patients with severe mental illness.3,4

The general population has benefited from the improved cardiovascular prevention and treatment, exemplified by, for instance, antithrombotic treatment reducing the risk of cardiovascular diseases, in particular stroke.5 Patients with severe comorbid mental disorders have not experienced the same improvement. The causes for this inequity may be found at the individual level regarding health personnel’s approach to treatment of patients with somatic disorders who have mental comorbidity and, at the organizational level, how somatic and psychiatric care can be integrated to improve physical health in patients with psychiatric illness.

Vitamin K antagonists, such as warfarin, have been the mainstay of OAT for patients with AF for more than 5 decades. The close monitoring and potential interaction of these agents with diet and other drugs is demanding both for patients and physicians and even more so in patients with mental illness comorbidity. The introduction of NOACs has simplified OAT regimens, and findings of the Danish study suggest that there has been an improvement also in the initiation of OAT in AF patients with mental illness after the introduction of these drugs.2 The message of this observation, as the authors state, is that patients with psychiatric comorbidity may face disparity in stroke prevention after development of AF, but they may benefit from increasing access to newer OAT.

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Article Information

Published: May 17, 2021. doi:10.1001/jamanetworkopen.2021.10116

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Thelle DS. JAMA Network Open.

Corresponding Author: Dag S. Thelle, MD, PhD, Institute of Basic Medical Sciences, University of Oslo, Postboks 1110 Blindern, N-0317 Oslo, Norway (

Conflict of Interest Disclosures: None reported.

Nielsen  RE, Banner  J, Jensen  SE.  Cardiovascular disease in patients with severe mental illness.   Nat Rev Cardiol. 2021;18(2):136-145. doi:10.1038/s41569-020-00463-7 PubMedGoogle ScholarCrossref
Fenger-Grøn  M, Vestergaard  CH, Ribe  AR,  et al  Association between bipolar disorder or schizophrenia and oral anticoagulation use in danish adults with incident or prevalent atrial fibrillation.   JAMA Netw Open. 2021;4(5):e2110096. Google Scholar
Laursen  TM, Munk-Olsen  T, Agerbo  E, Gasse  C, Mortensen  PB.  Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder.   Arch Gen Psychiatry. 2009;66(7):713-720. doi:10.1001/archgenpsychiatry.2009.61 PubMedGoogle ScholarCrossref
Manderbacka  K, Arffman  M, Suvisaari  J,  et al.  Effect of stage, comorbidities and treatment on survival among cancer patients with or without mental illness.   Br J Psychiatry. 2017;211(5):304-309. doi:10.1192/bjp.bp.117.198952 PubMedGoogle ScholarCrossref
Hart  RG, Pearce  LA, Aguilar  MI.  Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.   Ann Intern Med. 2007;146(12):857-867. doi:10.7326/0003-4819-146-12-200706190-00007 PubMedGoogle ScholarCrossref
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