Risk of adverse outcomes associated with mirtazapine compared to sertraline use among older people living in long-term care facilities

Abstract

Background Antidepressants are used by 60% of residents of long-term care facilities (LTCFs). Mirtazapine and sertraline are the most commonly used antidepressants, despite little safety information for their use in LTCFs. Objective To investigate risk of adverse outcomes (falls, fractures, cardiovascular-, dementia-, and delirium-related hospitalisations, all-cause mortality) associated with mirtazapine compared to sertraline use post-LTCF entry. Design Active new user retrospective cohort study. Subjects Individuals aged 65–105 years entering LTCFs in three Australian states during 1 January 2015 to 31 October 2018, who initiated mirtazapine or sertraline ≤60 days post-LTCF entry, with follow-up to 31 December 2019. Methods The inverse probability of treatment weighting of individuals’ propensity scores was used to adjust Cox and Fine–Gray regression models to estimate the risk of outcomes of interest associated with mirtazapine compared to sertraline use in LTCFs. Weighted (adjusted) hazard ratios (aHRs), subdistribution hazard ratios and 95% confidence intervals (95% CIs) are presented. Results A total of 5409 residents initiated mirtazapine (71%, n = 3837) or sertraline (29%, n = 1572) post-LTCF entry. After weighting, mirtazapine was associated with a higher risk of mortality (aHR 1.16, 95% CI 1.05–1.29) compared to sertraline. The risk of falls and fractures within 90 days was not statistically significantly different between the groups but was lower in mirtazapine users thereafter. No differences in risk of cardiovascular-, dementia- or delirium-related hospitalisations were observed. Conclusions Compared to sertraline, mirtazapine use is associated with a higher risk of mortality and, after 90 days of use, a lower risk of falls and fractures. This risk of harm should be balanced with limited evidence for effectiveness when considering antidepressant therapy in LTCFs.