Atypical Antipsychotics Augmentation in Patients with Depressive Disorder and Risk of Subsequent Dementia: A Nationwide Population-Based Cohort Study

Article type: Research Article

Authors: Kim, Jaehyun^a | Ha, Tae Hyon^b | Kim, Kiwon^c | Lee, Eun-Mi^d | Kim, Hyekyeong^e | Kim, Doh Kwan^f | Won, Hong-Hee^g | Lewis, Matthew^h | Lee, Hyewon^{i; j; 1; *} | Myung, Woojae^{b; 1; *}

Affiliations: [a] Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea | [b] Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea | [c] Department of Psychiatry, Veteran Health Service Medical Center, Seoul, South Korea | [d] Department of Health Science, Dongduk Women’s University, Seoul, South Korea | [e] Department of Health Convergence, College of Science and Industry Convergence, Ewha Womans University, Seoul, Republic of Korea | [f] Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea | [g] Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Gangnam-gu, Seoul, Republic of Korea | [h] The Department of General Practice, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia | [i] Department of Health Administration and Management, College of Medical Sciences, Soonchunhyang University, Asan, South Korea | [j] Department of Software Convergence, Soonchunhyang University Graduate School, Asan, South Korea

Correspondence: [*] Correspondence to: Woojae Myung, MD, PhD, Department of Neuropsychiatry, Seoul National University Bundang Hospital 29, Gumi-ro 173 beon-gil Bundang-gu, Seongnam-si, Gyeonggi-do 13619, South Korea. Tel.:+82 31 787 7430; Fax:+82 31 787 4058; E-mail: wjmyung@snubh.org and Hyewon Lee, PhD, Department of Health Administration and Management, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Asan 31538, South Korea. Tel.:+82 41 530 3045; Fax:+82 41 530 3085; E-mail: hwlee@sch.ac.kr.

Note: [1] These authors contributed equally to this work

Abstract: Background:While atypical antipsychotic medications are widely used for treating depressive disorders, their long-term effects on the risk of subsequent dementia have not been studied adequately. Objective:To investigate whether the risk of dementia differs according to the use of atypical antipsychotic drugs, and compare the effects of antipsychotic agents on dementia risk in individuals with late-life depressive disorders. Methods:A nationwide population-based retrospective cohort study was conducted using data from the National Health Insurance Service—Senior Cohort of South Korea. Atypical antipsychotic dosages were standardized using a defined daily dose, and the cumulative dosage was calculated. Participants were observed from January 2008 to December 2015. Cox proportional hazard regression analysis was used to estimate the hazard ratios. Results:The cohort included 43,788 elderly adults with depressive disorders: 9,901 participants (22.6%) were diagnosed with dementia. Findings showed that atypical antipsychotics were prescribed to 1,967 participants (4.5%). Compared with non-users, users of atypical antipsychotics experienced a significantly higher risk for dementia with an adjusted hazard ratio (aHR) of 1.541 (95% confidence interval [CI], 1.415–1.678). A cumulative dose-response relationship was observed (test for trend, p < 0.0001). Among atypical antipsychotics, risperidone displayed the highest risk for dementia (aHR 1.767, [95% CI, 1.555–2.009]). Conclusion:In this study of elderly individuals with depressive disorders, atypical antipsychotic use was associated with a significantly higher risk of subsequent dementia. Healthcare professionals should be aware of this potential long-term risk. A limitation that should be mentioned is that we could not exclude patients with bipolar depression.

Keywords: Antipsychotic agents, dementia, depression, mood disorders

DOI: 10.3233/JAD-200994

Journal: Journal of Alzheimer's Disease, vol. 80, no. 1, pp. 197-207, 2021