JAMA Oncol

Lorazepam-based sedation reduces agitation in end-of-life delirium

October 6, 2025

Study details: This multicenter, double-blind, randomized clinical trial enrolled 75 patients with advanced cancer and persistent agitated delirium across palliative care units in Taiwan and the U.S. Participants were randomized to receive scheduled IV haloperidol, lorazepam, haloperidol plus lorazepam, or placebo every 4 hours. Primary outcome was change in Richmond Agitation-Sedation Scale (RASS) scores over 24 hours.

Results: Lorazepam alone and in combination with haloperidol significantly reduced agitation compared with haloperidol alone (mean RASS difference, −2.1 and −2.0, respectively; both p<.01). No significant difference was found between haloperidol and placebo. Rescue medication use was lowest in the lorazepam and combination groups (32% and 37%) and highest in the placebo group (83%). Adverse events and survival were similar across groups.

Clinical impact: For patients with refractory agitated delirium at end-of-life, scheduled lorazepam—alone or with haloperidol—offers superior symptom control over haloperidol monotherapy. These findings support a shift toward proactive, proportional sedation strategies using benzodiazepines in palliative care.

Source:

Hui D, et al. (2025, July 31). JAMA Oncol. Proportional Sedation for Persistent Agitated Delirium in Palliative Care: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40742738/