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Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

The study aimed to fill existing knowledge gaps on the safety of antidepressant drugs (ADs) by estimating the risk of hospitalization for arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs) and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV) events.

Methods

The cohort was composed by 199,569 individuals aged ≥ 65 years from five Italian healthcare territorial units who were discharged for cardiovascular outcomes in the years 2008–2010. The 17,277 patients who experienced hospital admission for arrhythmia during follow-up were included as cases. Odds of current ADs use among cases (i.e., 14 days before hospital admission) was compared with (i) odds of current use of 1:5 matched controls (between-patients case-control) and with (ii) odds of previous use during 1:5 matched control periods (within-patient case-crossover). The risk of arrhythmia associated with ADs current use was modelled fitting a conditional logistic regression. A set of sensitivity analyses was performed to account for sources of systematic uncertainty.

Results

Current users of SSRIs and NAAs were at increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95% confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of arrhythmia was associated with current use of trazodone (NAA) consistently in case-control and case-crossover designs.

Conclusions

Evidence that current use of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly with CV disease was consistently supplied by two observational approaches.

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Acknowledgements

This study was funded by a research grant from the AIFA—the Italian Medicines Agency (AIFA, project AIFA-FARM9LBBBL), Rome, Italy. Data analyses were performed at the Laboratory of Healthcare Research & Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano-Bicocca with grants from the Italian Ministry of Education, University and Research (“Fondo d’Ateneo per la Ricerca” portion, year 2015).

I-GrADE members: Nera Agabiti, Claudia Bartolini, Roberto Bernabei, Alessandra Bettiol, Stefano Bonassi, Achille Patrizio Caputi, Silvia Cascini, Alessandro Chinellato, Francesco Cipriani, Giovanni Corrao, Marina Davoli, Massimo Fini, Rosa Gini, Francesco Giorgianni, Ursula Kirchmayer, Francesco Lapi, Niccolò Lombardi, Ersilia Lucenteforte, Alessandro Mugelli, Graziano Onder, Federico Rea, Giuseppe Roberto, Chiara Sorge, Michele Tari, Gianluca Trifirò, Alfredo Vannacci, Davide Liborio Vetrano, Cristiana Vitale

Author Contributions

GC generated the study idea and wrote the final manuscript. AB performed all statistical analyses. All authors abstracted the data, authorized their utilization, and contributed to their interpretation and to the final manuscript by approving the final version.

Author information

Authors and Affiliations

  1. Laboratory of Healthcare Research & Pharmacoepidemiology, Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy

    A. Biffi, F. Rea, L. Scotti & G. Corrao

  2. Department of Neurosciences, Psychology, Drug Research and Children’s Health, University of Florence, Florence, Italy

    A. Mugelli, E. Lucenteforte & A. Bettiol

  3. Treviso Local Health Unit, Treviso, Italy

    A. Bettiol & A. Chinellato

  4. Department of Geriatrics, Neurosciences and Orthopaedics, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore, Rome, Italy

    G. Onder

  5. Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy

    C. Vitale

  6. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy

    N. Agabiti

  7. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy

    G. Trifirò

  8. Epidemiology Unit, Regional Agency for Healthcare Services of Tuscany, Florence, Italy

    G. Roberto

Authors
  1. A. Biffi
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  7. A. Chinellato
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  8. G. Onder
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  9. C. Vitale
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  12. G. Roberto
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Consortia

on behalf of the Italian Group for Appropriate Drug prescription in the Elderly (I-GrADE)

Corresponding author

Correspondence to A. Biffi.

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Conflict of interest

EL received research support from the Italian Agency of Drug (AIFA).

AM received research support from the Italian Agency of Drug (AIFA), the Italian Ministry for University and Research (MIUR), Gilead, and Menarini. In the last 2 years, he received personal fees as speaker/consultant from Menarini Group, IBSA, Molteni, Angelini, and Pfizer Alliance. None of these are related to this study.

GT leads an academic pharmacoepidemiology team which runs project that are sponsored by pharmaceutical companies and that are not related to the topic of the paper.

GC received research support from European Community (EC), European Medicine Agency (EMA), Italian Agency of Drug (AIFA), Italian Ministry of Health, and Ministry of Education, University and Research (MIUR). He took part to a variety of projects that were funded by pharmaceutical companies (i.e., Novartis, GSK, Roche, AMGEN, and BMS). He also received honoraria as a member of the Advisory Board from Roche. None of these are related to this study. All other authors declare that they have no conflict of interest.

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Biffi, A., Rea, F., Scotti, L. et al. Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy. Eur J Clin Pharmacol 74, 119–129 (2018). https://doi.org/10.1007/s00228-017-2352-x

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  • DOI: https://doi.org/10.1007/s00228-017-2352-x

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