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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
Abstract
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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“Novel analytical methods such as propensity score weighting using generalized boosted modeling may help to overcome the limitations of traditional analysis (e.g., Kemp et al., 2014), but are yet to be applied to associations between HRV and wellbeing.”
From The Complex Construct of Wellbeing and the Role of Vagal Function (2022) · cites this paper as Kemp et al., 2014
In the citing paper
“Interestingly, the basal heart rate was lower in patients taking SSRIs (mean=65.40 bpm, p=0.003, d=0.161) than in patients taking the placebo (Table 1).”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [28]
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“…with previous studies, which reported higher HR and reduced HRV in the context of clinical anxiety (for meta-analysis, see Chalmers et al., 2014; Hsin-An et al., 2020; Kemp et al., 2014; Melzig et al., 2009) and depressive disorders (Agelink et al., 2002; Kemp et al., 2010; Koenig et al., 2016).”
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“, 2013) and generalized anxiety disorder (Chalmers et al., 2014; Kemp et al., 2014).”
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“both selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are associated with decreased HRV [12] and an elevated inflammatory marker [13].”
BackgroundHistorical Development of HRV Analysis
Voss, A. (2017) · CRC Press eBooks · doi:10.4324/9781315372921-2
“Similar reductions in HRV have been found in depression (Thayer et al. 1998), generalized anxiety disorder (Thayer et al. 1996; Kemp et al. 2014), and posttraumatic stress disorder (Cohen et al. 1999).”
BackgroundLa funzione vagale: un link fra psiche, cervello e corpo
Minelli, A., & Palma, M. D. (2022) · PNEI REVIEW · doi:10.3280/pnei2022-001003
Antidepressants: Indications, Contraindications, Interactions, and Side Effects
Corponi, F., Fabbri, C., & Serretti, A. (2022) · Springer eBooks · doi:10.1007/978-3-030-62059-2_29
Cardiovascular eff ects of psychotropic drugs
Vardanyan, Y. Т. (2023) · Clinical Medicine (Russian Journal) · doi:10.30629/0023-2149-2023-101-9-10-467-473
Agorastos, A. (2023) · Research Publications (Maastricht University) · doi:10.26481/dis.20231211aa
Kapfhammer, H. (2023) · Springer eBooks · doi:10.1007/978-3-662-68309-5_1
Ma, C.-C., Yang, C.-Y., Chang, W., Sack, A. T., Chang, C.-C., & Chang, H. (2025) · Medicina · doi:10.3390/medicina61091522
“Moreover, in our sample, HRV nearly returned to normal levels after agome-latine treatment—an outcome rarely seen with other antidepressants [20,45,46].”
Kita, E., Nakayama, N., Niihara, M., Moriwaki, Y., Kono, A., Ookabe, S., Iwata, C., & Kurita, M. (2025) · BioPsychoSocial Medicine · doi:10.1186/s13030-025-00344-w
Bucurica, S., Toader, I., Pistol, C., Maniu, I., & Săvulescu-Fiedler, I. (2026) · Biology · doi:10.3390/biology15030266 · Cited by 1
Jiang, D., Chen, W., Qin, N., Li, L., Wang, S. W., Zhang, N., Huang, J., He, J., & Wang, C. (2026) · Frontiers in Psychology · doi:10.3389/fpsyg.2026.1833260
“HRV has been proposed as a marker of autonomic regulation in depression, although findings have been heterogeneous across studies (Huang et al., 2018; Kemp et al., 2014).”
Burkart, M., Scheer, S. P., Backhausen, L. L., Wekenborg, M., Beyer, N., McDonald, M., Roessner, V., & Vetter, N. C. (2026) · Clinical Neurophysiology Practice · doi:10.1016/j.cnp.2026.08.002
“…results were reported in other research designs (Alvares et al., 2016; Fiani et al., 2023), several large longitudinal studies and a general population-based study reported adverse effects, i.e. reductions, on HRV (Hu et al., 2019; Kemp et al., 2014; Licht et al., 2010; Tegegne et al., 2018).”
Tomasi, J., Tiwari, A., Zai, C., Zai, G., Richter, M., Sanches, M., Lachman, R., Gaspar, C., Cella, M., Greer, B., et al. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.122508
Metadata
- Authors
- Kemp, A. H., Brunoni, A. R., Santos, I. S., Nunes, M. A., Dantas, E. M., Carvalho de Figueiredo, R., Pereira, A. C., Ribeiro, A. L. P., Mill, J. G., Andreão, R. V., Thayer, J. F., Benseñor, I. M., & Lotufo, P. A.
- Affiliations
- The University of Sydney (AU)
- 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...
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2014-12-01
- Volume
- 171
- Issue
- 12
- Pages
- 1328-1334
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2119976990
- Cited by
- 189
- References
- 41
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 17 · 2022: 13 · 2021: 18 · 2020: 15 · 2019: 18 · 2018: 14 · 2017: 16 · 2016: 27 · 2015: 24 · 2014: 2
- FWCI
- 15.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- resting heart rate, heart rate variability, depression, anxiety disorders, antidepressants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, generalized anxiety disorder, cardiovascular risk, mood disorders, ELSA-Brasil
- MeSH terms
- Adult, Aged, Antidepressive Agents, Antidepressive Agents, Tricyclic, Anxiety, Anxiety Disorders, Brazil, Cardiovascular Diseases, Depression, Major Depressive Disorder, Female, Heart Rate, Humans, Interview, Psychological, Longitudinal Studies, Male, Middle Aged, Vagus Nerve, Comorbidity, Selective Serotonin Reuptake Inhibitors, Adrenergic Uptake Inhibitors, Mood Disorders, Propensity Score
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