Associations between risk of mortality and atypical antipsychotic use in vascular dementia: a clinical cohort study

Objectives: People with vascular dementia (VaD) are frequently prescribed atypical antipsychotics to treat behavioural and psychological symptoms, but there is an alarming lack of evidence regarding their safety or efficacy in VaD. This study sought to identify the mortality risk associated with the most commonly prescribed atypical antipsychotics in people with VaD compared with people not exposed to these drugs.

Methods: A clinical cohort study of 1531 people with VaD performed using anonymised versions of full electronic health records from the Clinical Record Interactive Search application at the South London and Maudsley NHS Foundation Trust. Patients were identified from 2007 to 2010, of whom 337 were exposed to quetiapine, risperidone or olanzapine. The main outcome measure was mortality.

Results: Patients exposed to atypical antipsychotics were not at increased risk of mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI): 0.87-1.26]. Exposure to risperidone did not result in an increased risk of mortality (HR = 0.85; 95% CI: 0.59-1.24), and patients exposed to quetiapine had a non-significant numerical increase in mortality risk (HR = 1.14; 95% CI: 0.93-1.39; p-value = 0.20) compared with untreated patients. Too few patients were exposed to olanzapine alone to provide reliable results.

Conclusions: The absence of a significant increase in mortality risk associated with atypical antipsychotics in people with VaD indicates that a clinical trial of antipsychotics focussing on the treatment of aggression and agitation in this patient group will be justified and feasible following further consideration of possible confounders, which will be critical to determine the role of antipsychotics in treatment of VaD.