Kayla Peltier, Mercer University College of Pharmacy
Delirium has been identified as the most common serious neuropsychiatric complication in cancer patients. First-line treatment for delirium is often non-pharmacological and includes re-orienting the patient frequently, encouraging cognitively stimulating activities, avoiding immobility if possible, and promoting good sleep patterns and sleep hygiene. If non-pharmacological therapies are not effective or the patient is displaying severe agitation and poses a risk to self-harm or harm others, then treatment with pharmacological agents (including antipsychotic and sedating medications) may be considered. 
The authors of the study state that while antipsychotics and benzodiazepines are often used to treat delirium, the use of benzodiazepines is controversial due to a lack of adequate, well-controlled randomized trials. Therefore, this study aims to compare the effect of lorazepam to placebo as an adjuvant to haloperidol therapy in patients with agitated delirium in the setting of advanced cancer. 
|Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial|
|Design||Single-center, double-blind, parallel-group, randomized clinical trial; N= 90|
|Objective||To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer|
|Study Groups||Lorazepam + haloperidol (L+H; n= 47; 29 included in primary analysis)
Placebo + haloperidol (P+H; n= 43; 29 included in primary analysis)
– 18 years and older
– Diagnosis of delirium by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, in the opinion of the attending physician and bedside nurse
– History of agitation with a Richmond Agitation-Sedation Scale (RASS) score of 2 or more over the past 24 hours despite receiving scheduled haloperidol of 1 mg to 8 mg per day
– Use of benzodiazepines or chlorpromazine within the past 48 hours
– Contraindications to neuroleptics (e.g. Parkinson disease, myasthenia gravis, acute narrow-angle glaucoma, seizure disorders, documented corrected QT interval prolongation, or hypersensitivity)
– Contraindications to benzodiazepines (e.g. hypersensitivity)
Patients with hyperactive or mixed delirium were allocated in a 1:1 ratio to receive lorazepam 3 mg intravenously (IV) or placebo in addition to haloperidol. Patients were routinely treated for any potentially reversible causes and provided with non-pharmacologic measures and intensive symptom management. After randomization, patients were initiated on a standard dose of haloperidol 2mg IV every 4 hours and another 2 mg every hour as needed for agitation. The RASS score for every patient was monitored every two hours until the score was 2 or more and required rescue medication according to the bedside nurse’s judgment before administering the treatment options. Once treatment threshold was obtained, a single dose of 3 mg of lorazepam or an identical placebo was infused over 1.5 minutes, then all patients received 2 mg of haloperidol immediately afterwards. The use of other medications and withholding of scheduled haloperidol was permissible as per standard of practice according to the clinical judgement of the attending physician and bedside nurse.
|Duration||February 2014 – June 2016|
|Primary Outcome Measure||Change in RASS (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration|
|Adverse Events||Common Adverse Events
|Serious Adverse Events: One patient (3%) in L+H group and three patients (10%) in P+H group died within 8 hours of study medication administration.|
|Study Author Conclusions||The addition of lorazepam to haloperidol significantly reduces agitation at 8 hours in patients with advanced cancer when compared to treatment with haloperidol alone.|
This preliminary study demonstrates that the addition of lorazepam to haloperidol compared to haloperidol alone produced a significant reduction in agitation at eight hours in advanced cancer patients with agitated delirium.
 Alexander K, Goldberg J, Korc-grodzicki B. Palliative Care and Symptom Management in Older Patients with Cancer. Clin Geriatr Med. 2016;32(1):45-62.
 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: A Randomized Clinical Trial. JAMA. 2017;318(11):1047-1056.