A Post-Authorization Safety Study of Quetiapine as Antidepressant Treatment in Sweden: Nested Case–Control Analyses of Select Outcomes

Introduction This post-authorization safety study (PASS) was a commitment to the European Medicines Agency. Objective This PASS investigated quetiapine as antidepressant treatment in Swedish registers with regard to the risk for all-cause mortality, self-harm and suicide, acute myocardial infarction, stroke, diabetes mellitus, extrapyramidal disorders, and somnolence. Methods Users of quetiapine and antidepressants (2011‒2014) who had changed treatment in the past year were included. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for each outcome in nested case–control studies for quetiapine as combination therapy and monotherapy, monotherapy with antidepressants, and no medication, versus the use of combinations of antidepressants (reference group). Results Overall, 7421 quetiapine users and 281,303 antidepressant users were included. For quetiapine in combination, risks were increased for all-cause mortality [adjusted OR (aOR) 1.31, 95% CI 1.12–1.54] compared with combinations of antidepressants; however, when stratified by age, only patients ≥ 65 years of age had an increased mortality, and, in a post hoc analysis excluding patients with Parkinson’s disease, no mortality increase remained. Furthermore, the risk for self-harm and suicide was increased (aOR 1.53, 95% CI 1.31–1.79), but when stratified by age, the risk increase was found only among patients aged 18–64 years. Risks were also increased for stroke among patients ≥ 65 years of age (aOR 1.47, 95% CI 1.01–2.12), for extrapyramidal disorder (aOR 6.15, 95% CI 3.57–10.58), and for somnolence (aOR 2.41, 95% CI 1.42–4.11). Conclusion Risks for all-cause mortality, self-harm and suicide, and stroke in older patients may be higher among patients treated with quetiapine and antidepressant combination therapy.