Adverse Outcomes Associated With Off-Label Agents Used to Treat Dementia Patients With Psychosis: A Case-Control Medicare Database Study

Abstract

Introduction Currently, there are no Food and Drug Administration-approved therapies to treat dementia-related psychosis (DRP). This study investigated the association between using antipsychotics and the anticonvulsant divalproex (sodium valproate) to manage DRP and adverse outcomes. Methods A retrospective case/control matching study evaluated the risk of mortality, extrapyramidal symptoms (EPS), ischemic stroke, and cardiac arrest/ventricular arrhythmia (CA/VA) with ever-use of antipsychotics/divalproex in patients with DRP vs never-use. Results 49 509 patients were included; 76.8% used an antipsychotic/divalproex. Treatment ever-use was associated with an increased risk of all-cause mortality (odds ratio, 1.14; 95% CI, 1.10-1.18) and a smaller increase in the risk of EPS (1.10; 1.00-1.19) relative to never-use (adjusted for matching demographic variables, comorbid conditions, and disability) . Conclusions Current agents used for DRP were associated with increased risk of death and adverse outcomes. An increased risk of death was evident within 3 months of antipsychotic/divalproex initiation and persisted with long-term use.

Gone Too Soon: priorities for action to prevent premature mortality associated with mental illness and mental distress

“…52,55,56 The benefits versus risks of increased mortality vary by the types of medications, comorbidities and course of the mental illness. 54,57 Limited access to appropriate medication in LMICs contributes to health disparities in the effective treatment of mental illness and associated physical health conditions. Among others, physical and mental illnesses are known risk factors for suicide.…”