Anticholinergic burden as a precipitating factor for delirium spectrum disorders in schizophrenia spectrum and bipolar disorders: A case-crossover study based on the French nationwide claims database

Delirium spectrum disorders (DSD) are acute conditions marked by cognitive disturbance and altered consciousness associated with prolonged hospitalization. Schizophrenia spectrum and bipolar disorders are severe and persistent mental disorders (SPMD) predisposing to delirium. Many medications for SPMD have anticholinergic properties, a known precipitating factor for delirium in older people. We investigated the age threshold beyond which high anticholinergic burden becomes a significant precipitating factor for DSD in SPMD. We identified adults with SPMD with DSD diagnoses during non-psychiatric hospitalizations (2012-2022) using data from one of the largest claims databases, i.e., the French nationwide claims database, enabling the study of such an underdiagnosed event. In a case-crossover design with an active control period, we compared anticholinergic burden before the hospitalization with a DSD diagnosis with that before a control hospitalization for the same patient, controlling for variables stable in time. Over an 11-year period, 8.9 % of adults with SPMD received a diagnosis of DSD during hospitalization. High anticholinergic burden was significantly associated with higher risks of in-hospital DSD in patients aged >60 years (OR (95 % CI) = 1.11 (1.04-1.18)), but not in younger adults. Electrolyte imbalance, urodigestive disorders, anemia or hemorrhage, and substance use disorders, including tobacco use disorders, were significantly associated with a higher risk of in-hospital DSD diagnoses in all adults. Overall, at age 61, anticholinergic burden emerges as a risk factor for in-hospital DSD in individuals with SPMD, while somatic precipitating factors are a concern for all adults with SPMD.