Mortality risk associated with haloperidol use compared to other antipsychotics: An 11-year population-based propensity-score-matched cohort study

Abstract

Background: Haloperidol is a frequently prescribed antipsychotic worldwide. However, the mortality risk of all‐cause, cardiovascular disease (CVD), and pneumonia associated with haloperidol compared with other antipsychotics is unknown. Objectives: This study is to investigate the risk of mortality associated with long‐term haloperidol treatment as compared with other antipsychotics. Methods: This is a cohort study using a population‐based electronic health record database. Patients on haloperidol or other antipsychotics (amisulpride, aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, sulpiride, and trifluoperazine) from 2004 to 2014 were matched on propensity score. The outcome was mortality of all‐cause, CVD, and pneumonia. Absolute rates of outcome were calculated in the number of deaths per 1000 person‐year follow‐ups. Relative risks of outcome were calculated in hazard ratios (HR) with 95% confidence intervals (95% CI) using the Cox proportional hazards model. Results: A total of 136 593 incident users of antipsychotic (44.7% male) were included with a mean age of 68 years (SD 22.3). Patients on haloperidol (n = 65 510 [48.0%]) were matched to patients on other antipsychotics. During a mean follow‐up of 3.2 person‐years, mortality rates by drug varied from 186.8 (per 1000 person‐year [haloperidol]) to 10.4 (per 1000 person‐year [trifluoperazine]). Compared with haloperidol, a lower risk of all‐cause mortality was shown in all non‐haloperidol antipsychotic drugs, with HRs by drug ranging from 0.68 (95% CI 0.64 to 0.72 [chlorpromazine]) to 0.43 (95% CI 0.36 to 0.53 [trifluoperazine]). Significantly lower pneumonia‐related mortality risk was observed with all non‐haloperidol antipsychotics except amisulpride and olanzapine, with HRs varying from 0.76 (95% CI 0.68‐0.85) for risperidone to 0.38 (95% CI 0.24‐0.61) for trifluoperazine. A significantly lower risk of CVD mortality was observed for risperidone (HR 0.79 [95% CI 0.66‐0.93]), sulpiride (HR 0.78 [95% CI 0.64‐0.96]), chlorpromazine (HR 0.76 [95% CI 0.65‐0.90]), and quetiapine (HR 0.67 [95% CI 0.57‐0.78]). Conclusions: Haloperidol is associated with an increased mortality risk compared with other antipsychotics in long‐term follow‐up. Treatment with haloperidol, especially in the elderly and patients at risk of CVD or pneumonia, should be cautiously reassessed while other antipsychotics associated with lower risk should be considered as a preferred option.