Patients with advanced cancer who present with agitated delirium may experience a greater reduction of agitation if treated with lorazepam plus haloperidol compared with haloperidol alone, a study published in JAMA has shown.

Treating patients with delirium with benzodiazepines is controversial not only due to a lack of evidence supporting their efficacy, but also because previous evidence suggested that lorazepam is inferior to haloperidol and chlorpromazine and has a worse toxicity profile. 

For this double-blinded study, researchers randomly assigned 90 patients from the palliative care unit with agitated delirium despite being treated with haloperidol to receive additional intravenous lorazepam 3 mg or placebo. The primary end point was change in Richmond Agitation-Sedation Scale (RASS) score from baseline to 8 hours after administering treatment.

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Approximately 90% of patients completed the study. Patients who received lorazepam plus haloperidol experienced a significantly greater reduction in RASS score of –4.1 points compared with –2.3 points for patients who received placebo plus haloperidol (mean difference, –1.9 points; 95% CI, –2.8 to –0.9; P <.001).

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Patients who received adjuvant lorazepam also required less median rescue neuroleptics (2.0 mg) compared with patients receiving placebo (4.0 mg; median difference, –1.0 mg; 95% CI, –2.0 to 0; P =.009). Nurses and caregivers also reported that patients who received lorazepam in addition to haloperidol seemed to be more comfortable. 

Investigators found no significant difference in delirium-related distress and survival between the groups.

The most frequently reported adverse event was hypokinesia, which occurred in 19% and 27% of patients receiving lorazepam and placebo, respectively.

Results of the study demonstrated that the addition of lorazepam to haloperidol provides greater control of agitation in patients with advanced cancer presenting with delirium, but the authors noted that “further research is needed to assess generalizability and adverse effects.”


1. Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care [published online September 19, 2017]. JAMA. doi: 10.1001/jama.2017.11468