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Effects of Depression, Anxiety, Comorbidity, and Antidepressants on Resting-State Heart Rate and Its Variability: An ELSA-Brasil Cohort Baseline Study
Andrew H. Kemp, Ph.D.; Andre R. Brunoni, M.D., Ph.D.; Itamar S. Santos, M.D., Ph.D.; Maria A. Nunes, M.D., Ph.D.; Eduardo M. Dantas, Ph.D.; Roberta Carvalho de Figueiredo, Ph.D.; Alexandre C. Pereira, M.D., Ph.D.; Antonio L.P. Ribeiro, M.D., Ph.D.; José G. Mill, M.D., Ph.D.; Rodrigo V. Andreão, Ph.D.; Julian F. Thayer, Ph.D.; Isabela M. Benseñor, M.D., Ph.D.; Paulo A. Lotufo, M.D., Dr.P.H.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.13121605
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The authors report no financial relationships with commercial interests.

Dr. Kemp is supported by an International Research Professorship from the University of São Paulo, Brazil. Dr. Ribeiro is supported by a research grant (Pesquisador Mineiro) from the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), the research agency of the state of Minas Gerais, Brazil. Dr. Brunoni is a recipient of a young investigator award from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), the research agency of the state of São Paulo, Brazil. The ELSA-Brasil baseline study was supported by the Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science and Technology (Financiadora de Estudos e Projetos and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, the national research council of Brazil) (grants 01 06 0010.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ). Drs. Kemp and Bensenor are recipients of funding from FAPESP and Ohio State University (2013/50327-6).

From University Hospital and the Faculty of Medicine, University of São Paulo, São Paulo, Brazil; the School of Psychology and Discipline of Psychiatry, University of Sydney, Sydney, Australia; the Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; the Collegiate of Biological Sciences, Federal University of Vale do São Francisco, Petrolina, Pernambuco, Brazil; Campus Centro Oeste Dona Lindu, Federal University of São João Del-Rei, Brazil; the Laboratory of Genetics and Molecular Cardiology, Heart Institute/InCor, University of São Paulo Medical School, São Paulo; Hospital das Clínicas and Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil; the Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil; and the Department of Psychology, Ohio State University, Columbus.

Presented in part at the annual meeting of the American Heart Association, Dallas, Nov. 16–20, 2013.

Address correspondence to Dr. Kemp (andrew.kemp@hu.usp.br or andrew.kemp@sydney.edu.au).

Copyright © 2014 by the American Psychiatric Association

Received December 09, 2013; Revised March 27, 2014; Revised May 29, 2014; Accepted June 16, 2014.


Objective  Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders.

Method  A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule–Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability.

Results  Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen’s d, 0.72–0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen’s d, 0.42–0.95) and other antidepressants (Cohen’s d, 0.37–0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting.

Conclusions  The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

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FIGURE 1. Key Findings Associated With the Impact of Antidepressants on Heart Rate and Its Variability After Propensity Score Weightinga

a lnRMSSD=log-transformed root mean square of successive difference; lnHF=log-transformed high-frequency component; SSRI=selective serotonin reuptake inhibitor; SNRI=serotonin and norepinephrine reuptake inhibitor. Error bars indicate 95% confidence intervals corresponding to the propensity score weighted regression. Antidepressant group sizes are follows: no antidepressant, N=14,069; SSRI, N=356; SNRI, N=52; tricyclic antidepressant, N=84; other antidepressant, N=75.



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