Antidepressants and the risk of death in older patients with depression: A population-based cohort study

PLoS One. 2019 Apr 15;14(4):e0215289. doi: 10.1371/journal.pone.0215289. eCollection 2019.

Abstract

Background: Antidepressants are frequently used in older patients with depression, but little is known about the comparative safety of individual agents. The objective of the study was to determine the comparative risk of death of antidepressants in older patients with depression.

Methods and findings: We carried out a cohort study from 2004 to 2015 utilizing the German Pharmacoepidemiological Research Database, a population-based database supplied by statutory health insurance providers covering approximately 17% of the general population and all geographical regions. We included 376,846 patients aged 65+ years with a diagnosis of depression who initiated treatment with one of 13 antidepressants (ADs). In total 27,019 patients died during follow-up corresponding to a rate of 119.7 per 1,000 person years. We used proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of death for twelve ADs compared to citalopram. In the primary analysis, we found an increased risk of death associated with the use of amitriptyline (HR 1.15, 95%CI: 1.10-1.20). However, opipramol, trimipramine, doxepin, mirtazapine, fluoxetine, paroxetine, duloxetine, venlafaxine, and St. John's wort were found to be associated with a lower risk of death. The increased risk of amitriptyline diminished after exclusion of patients with a history of cancer (HR 0.88, 95%CI: 0.82-0.94) and after high-dimensional propensity score (HdPS) adjustment (HR 1.04, 95%CI: 0.95-1.14). In older patients and in those with dementia, differences in risk between most individual ADs and citalopram were smaller. After adjustment by HdPS, the decreased risks for fluoxetine, paroxetine, venlafaxine and mirtazapine compared to citalopram disappeared.

Conclusions: This study suggests that ADs recommended as first-line treatment in patients with depression have a similar safety profile with regard to the risk of death, especially in very old patients and in those with dementia. Further research is needed to investigate the risk of death for individual ADs in specific subgroups such as patients with cancer or cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects*
  • Cohort Studies
  • Depression / drug therapy*
  • Depression / mortality*
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Risk Factors

Substances

  • Antidepressive Agents

Grants and funding

This study was funded by the German Federal Institute for Drugs and Medical Devices (BfArM): https://www.bfarm.de/DE/Home/home_node.html. Fund number: 73.05/3832-219949/12. The fund was received by the Leibniz Institute for Prevention Research and Epidemiology - BIPS. BK and TS are working and KJ, EG and NS were working at BIPS. JK is an employee of BfArM. The BfArM had no further role in study design; in the collection and analysis of the data; and in the decision to submit the paper for publication. The publication of this article was funded by the Open Access Fund of the Leibniz Association.