Comparison of Intramuscular Pharmacological Treatment Options for Acute Agitation: A Multicenter Retrospective Cohort Study

ObjectiveAcute agitation in psychiatric settings presents significant clinical and safety challenges. Pharmacological management is often necessary when de-escalation strategies fail, but optimal medication regimens remain unclear. This study evaluates the safety, efficacy, and adverse event profiles of commonly used intramuscular (IM) pharmacologic regimens for acute agitation in a multicenter cohort. MethodsWe conducted a retrospective cohort study using de-identified data extracted from the HCA Healthcare corporate database. Adult psychiatric patients who received PRN intramuscular medications for acute agitation were included. Patients were stratified into four treatment groups based on administered medication: (1) haloperidol monotherapy, (2) haloperidol + lorazepam, (3) haloperidol + diphenhydramine, and (4) haloperidol + lorazepam + diphenhydramine. Outcomes assessed included frequency of PRN use, benztropine administration, and incidence of hypotensive and hypoxic episodes. Generalized linear modeling was used for statistical analysis. ResultsThe combination regimen of haloperidol + lorazepam + diphenhydramine (Group 4) was associated with significantly higher odds of receiving multiple PRN administrations compared to haloperidol alone (Group 1). However, this regimen, along with the diphenhydramine-inclusive group (Group 3), was linked to a significantly lower likelihood of requiring benztropine, suggesting a reduction in extrapyramidal symptom burden. No statistically significant group differences were observed in hypotensive or hypoxic episodes. ConclusionTriple-agent regimens may be associated with increased treatment intensity but offer benefits in reducing extrapyramidal symptoms without increasing cardiovascular or respiratory risk. These findings support the thoughtful use of combination IM regimens, particularly those including diphenhydramine, in the management of acute agitation in psychiatric settings.