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

Chee-Kin Then; Nai-Fang Chi; Kuo-Hsuan Chung; Lynn Kuo; Kao-Hui Liu; Chaur-Jong Hu; Shing-Chuan Shen; Yen-Kuang Lin

doi:10.1371/journal.pone.0175187

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

PLoS One. 2017 Apr 6;12(4):e0175187. doi: 10.1371/journal.pone.0175187. eCollection 2017.

Authors

Chee-Kin Then^{1

2}, Nai-Fang Chi^{3

4}, Kuo-Hsuan Chung^{5

6}, Lynn Kuo⁷, Kao-Hui Liu^{8

9}, Chaur-Jong Hu^{3

4}, Shing-Chuan Shen², Yen-Kuang Lin¹⁰

Affiliations

¹ School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Department of Neurology, Shuang Ho Hospital, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
⁶ Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Department of Statistics, University of Connecticut, Storrs, Connecticut, USA.
⁸ Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
⁹ Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹⁰ Biostatistics Center, Taipei Medical University, Taipei, 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.

MeSH terms

Adult
Antidepressive Agents / therapeutic use*
Case-Control Studies
Dementia / drug therapy*
Female
Humans
Male
Middle Aged
Risk Assessment
Taiwan

Substances

Antidepressive Agents

Grants and funding

This work was supported by the Ministry of Science and Technology (MOST), Taiwan [grant numbers MOST 103-2320-B-038-024, MOST 105-2314-B-038-013-MY3]; the National Science Council (NSC), Taiwan [grant number NSC 102-2314-B-038-042, NSC 101-2314-B-038-013]; and Taipei Medical University (TMU) [grant number TMU104-F-004, TMU104-AE1-B09]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.