Atypical Antipsychotics Augmentation In Patients With Depressive Disorder And Risk Of Subsequent Dementia: A Nationwide Population-Based Cohort Study

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.