Arad Kodesh1, Sven Sandin2, Abraham Reichenberg3, Anat Rotstein4, Nancy L Pedersen5, Malin Ericsson5, Ida K Karlsson6, Michael Davidson7, Stephen Z Levine8. 1. Department of Community Mental Health, University of Haifa, Haifa, Israel; Meuhedet Health Services, Mental Health, Tel Aviv, Israel. 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; The Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY. 3. The Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY. 4. Department of Community Mental Health, University of Haifa, Haifa, Israel. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Institute of Gerontology and Aging Research Network - Jönköping (ARN-J), School of Health and Welfare, Jönköping University, Jönköping, Sweden. 7. Sackler Medical School, Tel Aviv University, Tel Aviv, Israel; Nicosia Medical School Nicosia, Cyprus. 8. Department of Community Mental Health, University of Haifa, Haifa, Israel. Electronic address: slevine@univ.haifa.ac.il.
Abstract
OBJECTIVE: To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia. METHODS: A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002-2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes. RESULTS: In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47. CONCLUSION: In this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment.
OBJECTIVE: To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia. METHODS: A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002-2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes. RESULTS: In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47. CONCLUSION: In this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment.
Authors: Mitzi M Gonzales; Jasmeet Samra; Adrienne O'Donnell; R Scott Mackin; Joel Salinas; Mini E Jacob; Claudia L Satizabal; Hugo J Aparicio; Emma G Thibault; Justin S Sanchez; Rebecca Finney; Zoe B Rubinstein; Danielle V Mayblyum; Ron J Killiany; Charlie S Decarli; Keith A Johnson; Alexa S Beiser; Sudha Seshadri Journal: J Alzheimers Dis Date: 2021 Impact factor: 4.472
Authors: Yun Freudenberg-Hua; Alexander Makhnevich; Wentian Li; Yan Liu; Michael Qiu; Allison Marziliano; Maria Carney; Blaine Greenwald; John M Kane; Michael Diefenbach; Edith Burns; Jeremy Koppel; Liron Sinvani Journal: Front Med (Lausanne) Date: 2022-03-18
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