For a study, the researchers evaluated the efficacy and security of haloperidol, lorazepam, and diphenhydramine (B52) in combination with haloperidol and lorazepam (52), in treating acute agitation. Adult patients under the age of more than or equal to 18 who received either B52 or 52 at a Banner Health institution between August 2017 and September 2020 were included in this multicenter, retrospective cohort trial. If a patient had a pre-existing movement issue or was detoxing from alcohol, they were ruled out. The primary outcome was the delivery of further agitation medication(s) within 2 hours of B52 or 52. Extrapyramidal symptom incidence, length of stay, and additional safety precautions were secondary outcomes. Additional agitation medication(s) were administered at the same frequency (B52: n=28 [14%] vs 52: n=40 [20%]; p=0.11). Within 2 days, patients who received 52 were more likely to need antimuscarinic medication (15 vs 6 patients, p=0.04). There were no extrapyramidal effects in any of the patients given an antimuscarinic drug. In comparison to the B52 group, the 52 groups had a shorter length of stay (13.8 vs 17 h; p=0.03), a lower incidence of hypotension (7 vs 32 patients; p<0.001), oxygen desaturation (0 vs 6 patients; p=0.01), and fewer physical constraints (53 vs 86 patients; p=0.001). Repeat agitation medication was required seldom in both the B52 and 52 combinations; however, the B52 combination resulted in higher oxygen desaturation, hypotension, physical restraint use, and a longer length of stay.