Comparative Safety of Haloperidol, Quetiapine and Risperidone in Elderly Patients with Stroke: Using Stroke Registry for External Adjustment

Background: Antipsychotics remain the first choice of treatment for post-stroke psychosis, despite an increased risk of mortality reported in elderly patients. We aimed to compare the mortality risk among antipsychotics in elderly patients with stroke using the stroke registry for external adjustment. Methods: We conducted a retrospective cohort study to identify patients aged above 65 years who were admitted for stroke in the National Health Insurance Database (NHID) from 2002 to 2014. The first date of antipsychotic use after the stroke hospitalization was defined as the index date. Covariates including diseases, medications and external information on smoking, BMI, stroke severity and disability, that were unavailable in the NHID were obtained from the linked Multicenter Stroke Registry (MSR) and used for propensity score calibration (PSC). The main outcome was one-year all-cause mortality Findings: Stroke patients in the NHID prescribed with haloperidol, quetiapine and risperidone numbered 22 235, 28 702 and 8 663, respectively. In the PSC-adjusted analyses, haloperidol [adjusted hazard ratio (aHR) = 1.22; 95% CI 1.18–1.27] and risperidone (aHR = 1.31; 95% CI 1.24–1.38) users had a higher mortality risk than quetiapine users. Haloperidol and risperidone exhibited a dose-response relationship with mortality risk after controlling for confounders. When the dosage was higher than 0.5 defined daily dose (DDD), haloperidol and risperidone users had a significant mortality risk as compared with those taking a lower dose. The sensitivity analyses showed similar patterns. Interpretation: In post-stroke elderly patients, quetiapine would be favored over risperidone and haloperidol at doses higher than 0.5 DDD. When haloperidol or risperidone is indicated, starting with a lower dose is suggested to avoid excess risk. Funding Statement: This research was supported in part by the Ministry of Science and Technology, Taiwan [grant number MOST 107-2320-B-006-035]. Declaration of Interests: The authors declare they have no conflict of interest with respect to this research study and paper. Ethics Approval Statement: The research protocol was approved by the Institutional Review Board of National Cheng Kung University Hospital (IRB No. A-EX-106-016).