Date Published: April 15, 2019
Publisher: Public Library of Science
Author(s): Bianca Kollhorst, Kathrin Jobski, Jutta Krappweis, Tania Schink, Edeltraut Garbe, Niklas Schmedt, Kenji Hashimoto.
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.
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.
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.
Depression is a common condition in older people with a reported prevalence of 1–4% for major depression and 4–13% for minor depression . Besides non-pharmacological interventions, e.g., cognitive-behavioral therapy, clinical guidelines recommend pharmacological treatment with antidepressants (ADs) [2, 3]. The choice of AD should be guided by the tolerability and safety of the medication as well as the patient’s preference and consideration of side effects such as constipation, sedation, dizziness, and weight gain .
In this large observational study, similar safety profiles were observed for several individual antidepressants and citalopram. When compared to citalopram, opipramol, trimipramine, doxepin, mirtazapine, fluoxetine, paroxetine, duloxetine, venlafaxine, and St. John’s wort were associated with a lower risks, but are most likely a result of confounding as differential risks tended toward a null effect in more homogenous subgroups, such as in older patients and in those with dementia, and after additional confounder adjustment by HdPS. The use of amitriptyline was associated with a 15% increased risk of death compared to citalopram, that diminished after exclusion of cancer patients, in patients ≥ 80 years and after additional confounder adjustment by HdPS.