Analysis of the Effects of Selective Serotonin (and Noradrenaline) Reuptake Inhibitors on the Risk of Dementia in Patients with Depression

Background: Previous studies focusing on the association between antidepressant use and dementia have reported controversial findings. Objective: This study aimed to compare the associations between the prescription of selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs) and the occurrence of dementia in patients with depression followed in Germany. Methods: This study included 20,215 patients aged 70-90 diagnosed with depression and treated in general or neuropsychiatric practices in Germany between 2010 and 2015 (index date). The main outcome of the study was the rate of dementia within 10 years after the first prescription of SSRIs or SNRIs. For the first set of survival analyses, patients were followed until they received a dementia diagnosis or until the end of their antidepressant therapy, whereas for the second set of survival analyses, patients were followed until they received a dementia diagnosis or had their last documented visit to the practice. Results: Ten years after the index date, the rate of dementia ranged from 17.3% in escitalopram users to 36.0% in citalopram users in the first analysis, and from 30.8% in fluoxetine users to 40.4% in citalopram users in the second analysis. In the first regression model, fluoxetine (hazard ratio [HR] = 0.58), venlafaxine (HR = 0.74), and duloxetine (HR = 0.74) were associated with a decreased dementia risk compared with citalopram. In the second model, only venlafaxine significantly decreased the odds of developing dementia (HR = 0.81). Conclusion: SSRIs and SNRIs were differentially associated with the risk of dementia in patients with depression in Germany.