CHICAGO—Combination therapy with lorazepam and haloperidol is more effective than haloperidol alone at easing agitated delirium in patients with advanced cancer at the end of life, according to clinical trial findings presented at the American Society of Clinical Oncology 2017 annual meeting.
“Delirium is one of the most common neuropsychiatric complications that occur in cancer patients, and can be extremely distressing to patients, caregivers and healthcare professionals,” said lead investigator David Hui, MD, MSc, of The University of Texas MD Anderson Cancer Center in Houston. “The use of lorazepam to control agitation in delirium is highly controversial because there has not been any placebo-controlled trials on this topic. Some clinicians worry that it could worsen delirium while others believe that it is effective. For the first time, this study examined the use of lorazepam versus placebo as an adjuvant to haloperidol for the control of an episode of agitation in cancer patients with delirium.”
Dr Hui and his colleagues conducted a double-blind trial that enrolled 58 patients with advanced cancer admitted to an acute palliative care unit with agitated delirium despite scheduled haloperidol to receive either lorazepam 3 mg intravenously (IV) or placebo, in addition to haloperidol 2 mg IV upon the onset of agitation. The primary outcome was the Richmond Agitation Sedation Scale (RASS) over the first 8 hours. The scale ranges from −5 (unarousable) to +4 (combative).
Of the 58 patients, 52 (90%) patients completed 8 hours of observation. RASS decreased significantly within 30 minutes of treatment in both arms, the investigators reported. The lorazepam/haloperidol arm experienced a significantly greater mean decline in RASS score than the haloperidol-only arm (−4.12 vs −2.27). In addition, patients in the lorazepam/haloperidol arm also required fewer doses of rescue medications for agitation. “Importantly, those who received lorazepam/haloperidol were perceived to be significantly more comfortable by both blinded caregivers and nurses than those treated with placebo/haloperidol,” Dr Hui pointed out.
The investigators found no between-arm differences in adverse effects or survival.
“This study supports the judicious use of lorazepam/haloperidol as rescue for an episode of agitated delirium,” said Dr Hui, an associate professor in the Department of Palliative Care and Rehabilitative Medicine at MD Anderson. “It also opens up the possibility of further studies to examine the role of benzodiazepines in the management of delirium.”
Hui D, Frisbee-Hume S, Wilson A, et al. Lorazepam as an adjuvant to haloperidol for agitated delirium at the end of life: A double-blind randomized controlled trial. J Clin Oncol 2017;35 (suppl; abstr 10003). Presented at the American Society of Clinical Oncology annual meeting in Chicago on June 2, 2017.