Risk of hospitalization for stroke associated with antipsychotic use in the elderly: A self-controlled case series

Abstract

Background: Antipsychotics are commonly used in the elderly despite a lack of safety data from randomized trials, particularly for the typical antipsychotics. Observational studies have investigated the association between antipsychotics and stroke but results vary, which may be due to lack of control for unmeasured confounding. Objective: To estimate the risk of hospitalization for stroke in elderly users of antipsychotics. Study Design and Setting: Using the Australian Government Department of Veterans' Affairs administrative claims dataset we utilized a self-controlled case series design to risk-adjust for potential unmeasured confounding. Risk periods prior to antipsychotic initiation were also included to search for evidence of confounding by indication. Unexposed patients were included to adjust for the increasing incidence of hospitalization for stroke with age. Results: There were 10638 patients aged ≥65 years with at least one hospitalization for stroke identified during the 4-year period from 1 January 2003 to 31 December 2006. Of these, 514 patients were initiated on typical anti-psychotics and 564 patients were initiated on atypical antipsychotics. Hospitalization for stroke was increased in the first week after initiation of a typical antipsychotic (incidence rate ratio [IRR] 2.3; 95% CI 1.3, 3.8). There was no evidence of an increased risk of hospitalization for stroke after initiation of atypical antipsychotics. The risk of hospitalization for stroke progressively increased in the weeks leading up to first-time antipsychotic treatment. However, while the risk of hospitalization for stroke in the week prior to initiating antipsychotic therapy was significantly increased for patients initiated on typical antipsychotics (IRR 7.2; 95% CI 5.3, 9.8), patients initiated on atypical antipsychotics had no excess risk in the same period (IRR 1.2; 95% CI 0.7, 2.3). Conclusions: The results of this study are consistent with randomized controlled trial evidence indicating that there is no increased risk of serious cerebrovascular events requiring hospitalization in patients taking atypical antipsychotics. No randomized controlled trial evidence is available on the risk of hospitalization for stroke with use of typical antipsychotics in the elderly. This study found a small but significantly increased risk of hospitalization for stroke immediately following the initiation of typical antipsychotics. Antipsychotics are likely to be initiated after hospitalization for stroke. This practice is likely to reflect the prescribing of antipsychotics during hospital admission for post-stroke complications such as delirium; however, the long-term effects of this practice are unknown.