I recently had an argument with a colleague from our department about how to treat delirium. She declared with a lot of certainty that benzodiazepines should be avoided, while I had the opinion that there is no reason to treat a delirium that is not associated with alcohol withdrawal different from delirium tremens. The latter is routinely treated with benzodiazepines such as diazepam (or clomethiazole).
It is correct that there is a paucity of data on the pharmacological treatment of delirium. All the more should attention be paid to a study published last week in the Journal of the American Medical Association (JAMA). David Hui and colleagues from the Department of Palliative Care, Rehabilitation and Integrative Medicine, MD Anderson Cancer Center, Houston, Texas, studied the efficacy of lorazepam in patients with advanced cancer and agitated delirium in palliative care (Hui et al., JAMA 2017).
Dementia was a contraindication for participation in the study. All patients had at least two days of delirium with documentation of agitation before starting the study intervention. They were on a treatment regimen of 2 mg haloperidol intravenously every four hours. 58 patients (mean age 65 years) received either lorazepam 3 mg intravenously of placebo in a randomized double-blind fashion. The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) from baseline to 8 hours after treatment administration. The score of this scale ranges from -5 (unarousable) to +4 (very agitated or combative). The baseline score in both groups was 1.6. In the group treated with haloperidol + lorazepam, the score decreased by 4.1 points at 8 hours, while the decrease was 2.3 points under haloperidol + placebo. This mean difference of 1.9 points was highly statistically significant (p < 0.001). Most of the effect was observed already at 0.5 hours post initiation of the experimental treatment.
With regard to secondary outcomes, haloperidol + lorazepam was also superior to haloperidol + placebo: patients treated with lorazepam required less rescue haloperidol, and this treatment was perceived to be more comfortable by both blinded caregivers and nurses. Delirium-related distress, survival and adverse effects were similar in both groups.
Delirium is extremely common in hospital settings, which is in sharp contrast to the lack of controlled treatment studies. Although the present study was conducted in a quite selected patient sample and although the authors admit that "further research is needed to assess generalizability and adverse effects", it should be considered an important milestone.