Impact of CNS medication burden and drug interactions on delirium in patients with advanced cancer: a multicenter prospective observational study

Delirium is a common neuropsychiatric complication in patients with advanced cancer. Central nervous system (CNS)-active medications are established risk factors for delirium; however, these patients often require polypharmacy for symptom management, resulting in a high medication burden and increased risk of drug-drug interactions (DDIs). The impact of CNS medication burden and DDIs on delirium remains unclear. This multicenter, prospective observational study examined the association between CNS medication burden, measured using the CNS standardized daily dose (SDD), DDIs, and delirium incidence, duration, and mortality in hospitalized patients with advanced cancer. Among 190 patients, 20% developed delirium. CNS SDD was associated with delirium risk (adjusted OR [aOR]: 1.04, 95% CI: 1.0004-1.08). In categorical analyses, patients with a CNS SDD ≥ 10 had a significantly higher risk of delirium (aOR: 4.29, 95% CI: 1.33-15.47). Potential DDIs increasing exposure to delirium-risk medications had an aOR of 4.14 (95% CI: 0.96-17.41). Although neither CNS SDD nor DDIs affected delirium duration, opioid burden was associated with increased mortality. CNS medication burden and DDIs may be important factors for delirium and clinical outcomes. These findings underscore the need for medication optimization and proactive DDI monitoring to reduce the risk of delirium and improve patient outcomes.