Drug Safety

pp 1–9 | Cite as

Antidepressants and the Risk of Hemorrhagic Stroke in the Elderly: a Nested Case–Control Study

  • Wiebke Schäfer
  • Christina Princk
  • Bianca Kollhorst
  • Tania SchinkEmail author
Original Research Article


Background and Purpose

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed in the elderly due to a more favorable risk profile than other antidepressants (ADs). However, SSRIs are associated with an increased risk of gastrointestinal bleeding, while evidence on the risk of hemorrhagic stroke (HS) is limited. Therefore, we compared the risk of HS associated with the use of ADs in the elderly.


Based on data from the German Pharmacoepidemiological Research Database (GePaRD), a case–control study matched on age, sex, and health insurance provider, nested in a cohort of incident users of ADs ≥ 65 years of age was performed. Cases were identified from hospital discharge diagnoses, and exposure was identified from outpatient prescriptions. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs).


Based on 4059 cases and 40,590 controls, an increased risk of HS was found in current use of SSRIs (OR 1.39, 95% CI 1.22–1.58), selective serotonin and noradrenaline reuptake inhibitors (1.69, 1.35–2.11), noradrenergic and specific serotonergic ADs (1.44, 1.22–1.69), and noradrenaline reuptake inhibitors (3.81, 1.54–9.43) compared with tri- and tetracyclic antidepressants. An increased risk of HS was seen in patients with a high baseline risk of bleeding and in patients with depression. The risk of HS varied between individual ADs.


Our study shows that the use of medications inhibiting serotonin and/or noradrenaline reuptake increases the risk of HS in patients aged 65 years and older and that the risk varies across individual ADs.



The authors would like to thank all SHIs who provided data for this study, namely AOK Bremen/Bremerhaven, DAK-Gesundheit, hkk Krankenkasse, and Die Techniker (TK). The authors would further would like to thank Franziska von Mandelsloh and Nadine Schlie for their help in developing the outcome definitions and defining potential confounding factors, as well as Marieke Niemeyer and Inga Schaffer for statistical programming of the matched cohort.

Compliance with Ethical Standards

Conflicts of Interest

Wiebke Schäfer, Bianca Kollhorst, and Tania Schink are employees of the Leibniz Institute for Prevention Research and Epidemiology – BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post-authorization safety studies (PASS) requested by health authorities. The studies and the resulting publications are not influenced by the pharmaceutical industry. Christina Princk is currently an employee at the Governmental Institute of Public Health of Lower Saxony, Hanover, Germany, and has no conflicts of interest that are directly relevant to the content of this study.

Ethical Approval

In Germany, the utilization of health insurance data for scientific research is regulated by the Code of Social Law. All involved SHIs, the German Federal (Social) Insurance, and the Senator for Science, Health and Consumer Protection in Bremen as their responsible authorities approved the use of the data for this study. Informed consent for studies based on the GePaRD is not required by law, and, according to the Ethics Committee of the University of Bremen, these studies are exempt from Institutional Review Board review.


No sources of funding were used to assist in the preparation of this study.

Supplementary material

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Supplementary material 1 (DOCX 21 kb)
40264_2019_837_MOESM2_ESM.docx (18 kb)
Supplementary material 2 (DOCX 19 kb)
40264_2019_837_MOESM3_ESM.docx (18 kb)
Supplementary material 3 (DOCX 18 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Leibniz Institute for Prevention Research and EpidemiologyBremenGermany

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