Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan

Abstract

Depression and dementia are common mental health problems and are associated in several ways. Early-life depression is associated with increased risk of later life dementia, and depression can present as a preclinical symptom or consequence of dementia. Despite the plausible relationship between these two clinical entities, the potential association between antidepressant medication and dementia has rarely been investigated. We conducted a 9-year retrospective analysis of Taiwan’s National Health Insurance Research Database (NHIRD), enrolling 5819 cases who had received prescriptions of antidepressants between 2003 and 2006, and 23,276 (with ratio of 1:4) age, sex, and index date-matched controls. The hazard ratio (HR) of dementia among antidepressant users with depression was 2.42 (95% confidence interval (CI): 1.15–5.10), for those without depression was 4.05 (95% CI: 3.19–5.15), compared to antidepressant non-users respectively. Among the 6 classes of common antidepressants used in Taiwan, the adjusted HRs were 3.66 (95% CI: 2.62–5.09) for SSRIs, 4.73 (95% CI: 2.54–8.80) for SNRI, 3.26 (95% CI: 2.30–4.63) for TCAs, 6.62 (95% CI: 3.34–13.13) for TeCA, 4.94 (95% CI: 2.17–11.24) for MAOI, and 4.48 (95% CI: 3.13–6.40) for SARI. Furthermore, the multivariate analysis result showed that the adjusted HRs of cumulative defined daily doses (cDDDs) were 3.74 (95% CI: 2.91–4.82), 3.73 (95% CI: 2.39–5.80) and 5.22 (95% CI: 3.35–8.14) for those who had cDDDs of <90, 90–180 and >180 compared to those who had taken no antidepressant medication. This is a retrospective study based on secondary data, hence, we could not claim causality between antidepressant medication and dementia. However, a potential association between antidepressant and occurrence of dementia after controlling for the status of depression was observed. Lack of patients’ data about smoking status and body mass index in NHIRD, which are considered related to dementia, was also a limitation in this study. In this study, we concluded that antidepressant medication is a potential risk factor for dementia, independent from any effect of depression itself.

Antidepressants, sertraline and paroxetine, increase calcium influx and induce mitochondrial damage-mediated apoptosis of astrocytes

“…Furthermore, a meta-analysis by Moraros et al revealed that antidepressant medication was associated with a 2-fold increase in odds of several cognitive impairments [ 25 ]. We also obtained consistent results of antidepressant medication being associated with an increased risk of dementia in our previous study [ 26 ]. According to those studies and integrating the idea of an astroglio-centric perspective of neurodegenerative diseases [ 6 ], we proposed to determine the effects of antidepressant on astrocytes in this study.…”

“…To the present, this is the first study to illustrate the possible mechanism of cytotoxicity of sertraline and paroxetine on astrocytes via calcium overload. This study is an extension of our previously published article on the potential risk of antidepressant medication [ 26 ]. Based on the fact that astrocyte dysfunction threatening the survival of neurons, we conclude that antidepressant-induced astrocyte apoptosis might be involved in the development of neurodegenerative diseases.…”

“…Our previous article suggested that several antidepressant users were more likely to develop dementia, regardless their depression status [ 26 ]. Several studies showed consistent results with our observation and will be further discussed.…”

Are Anticholinergic Medications Associated With Increased Risk of Dementia and Behavioral and Psychological Symptoms of Dementia? A Nationwide 15-Year Follow-Up Cohort Study in Taiwan

“…Therefore, this finding might also be related to the fact that Parkinson's disease and psychotic disorders have been associated with the risk of dementia as aforementioned. Several previous studies have reported the association between antidepressant usage and the risk factor for dementia (Lee et al, 2016;Then et al, 2017); nevertheless, our study revealed no such association between antidepressants with anticholinergic effects (most tricyclic antidepressants) and the risk of dementia. In addition, one study using the NHIRD database reported the association between antimuscarinics for an overactive bladder (OAB) and the subsequent dementia risk in patients with diabetes mellitus (Yang et al, 2017).…”

Increased Risk of Dementia in Patients with Antidepressants: A Meta-Analysis of Observational Studies

“…The characteristics of the selected studies are presented in Table 1 . The five included observational studies [ 15 – 19 ] were published between 2012 [ 19 ] and 2017 [ 18 ]. Among these studies, 3 were from Asia and 2 were from North America.…”