Clinical Drug Investigation

, Volume 38, Issue 7, pp 593–602 | Cite as

Adherence to Antidepressants and Mortality in Elderly Patients with Cardiovascular Disease

  • Annalisa Biffi
  • Lorenza Scotti
  • Federico Rea
  • Ersilia Lucenteforte
  • Alessandro Chinellato
  • Davide L. Vetrano
  • Cristiana Vitale
  • Nera Agabiti
  • Janet Sultana
  • Giuseppe Roberto
  • Alessandro Mugelli
  • Giovanni Corrao
  • on behalf of the Italian Group for Appropriate Drug prescription in the Elderly (I-GrADE)
Original Research Article


Background and Objective

Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality.


The cohort included 29,845 individuals aged ≥ 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008–2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012–2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered ≥ 75%) and outcome, by adjusting and stratifying for several covariates.


Patients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3–14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (− 1–38), 14% (7–20), 20% (13–26) and 13% (7–19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively.


Better adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.



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.

Compliance with ethical standards


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, University of Milano-Bicocca with grants from the Italian Ministry of Education, University and Research (’Fondo d’Ateneo per la Ricerca’ portion, year 2015).

Conflicts of interests

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 two years he received personal fees as speaker/consultant from Menarini Group, IBSA, Molteni, Angelini and Pfizer Alliance. GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA), and the Italian Ministry for 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 member of Advisory Board from Roche. AC received support for participation at pharmacological meetings (SIF) and honoraria as member of Advisory board on biological drugs. Other authors declare that they have no conflict of interest to disclose.

Supplementary material

40261_2018_642_MOESM1_ESM.pdf (17 kb)
Supplementary material 1 (PDF 16 kb)
40261_2018_642_MOESM2_ESM.pdf (21 kb)
Supplementary material 2 (PDF 21 kb)
40261_2018_642_MOESM3_ESM.pdf (263 kb)
Supplementary material 3 (PDF 263 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Annalisa Biffi
    • 1
  • Lorenza Scotti
    • 1
  • Federico Rea
    • 1
  • Ersilia Lucenteforte
    • 2
  • Alessandro Chinellato
    • 3
  • Davide L. Vetrano
    • 4
    • 5
  • Cristiana Vitale
    • 6
  • Nera Agabiti
    • 7
  • Janet Sultana
    • 8
  • Giuseppe Roberto
    • 9
  • Alessandro Mugelli
    • 2
  • Giovanni Corrao
    • 1
  • on behalf of the Italian Group for Appropriate Drug prescription in the Elderly (I-GrADE)
  1. 1.Laboratory of Healthcare Research and Pharmacoepidemiology, Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative MethodsUniversity of Milano-BicoccaMilanItaly
  2. 2.Department of Neurosciences, PsychologyDrug Research and Children’s Health, University of FlorenceFlorenceItaly
  3. 3.Treviso Local Health UnitTrevisoItaly
  4. 4.Department of Geriatrics, Neurosciences and Orthopaedics, A. Gemelli University HospitalUniversità Cattolica del Sacro CuoreRomeItaly
  5. 5.Aging Research Center, Department of Neurobiology, Health Care Sciences and SocietyKarolinska Institutet and Stockholm UniversityStockholmSweden
  6. 6.Department of Medical SciencesIRCCS San Raffaele PisanaRomeItaly
  7. 7.Department of EpidemiologyLazio Regional Health ServiceRomaItaly
  8. 8.Department of Biomedical and Dental Sciences and Morphofunctional ImagingUniversity of MessinaMessinaItaly
  9. 9.Epidemiology UnitRegional Agency for Healthcare Services of TuscanyFlorenceItaly

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