Category: Pharmacology & Therapeutics
Keywords: haloperidol, agitation, sedation (PubMed Search)
Diphenhydramine (B) has historically been utilized in combination with haloperidol 5mg (5) and lorazepam 2mg (2) in the treatment of acute agitation. The most common rationale for adding diphenhydramine is prevention of EPS, however literature to support this is lacking. A recently published paper examined diphenhydramine/haloperidol/lorazepam combination (B52) vs haloperidol/lorazepam combination therapy (52) to compare the need for additional agitation treatments as a surrogate for clinical efficacy.
This retrospective, multicentered noninferiority study included 400 emergency medicine patients, 200 per treatment arm. On average, the patients were 40 years old, 64% male, and predominantly Caucasian. More patients in the B52 group had psychiatric illness listed as their primary cause for agitation compared to the 52 group. The two most frequently reported substances on urine drug screens, if collected, were amphetamines (35%) and cannabinoid (35.5%).
-No difference in the use of additional agitation medications within 2 hours
-More patients in the 52 group were noted to receive anticholinergic medications within 2 days, but indications varied and were not associated with EPS treatment
The B52 combination was associated with:
---Increased length of stay 17 h (10-26) vs 13.8 h (9-12), p = 0.03
---Increased use of restraints 43% vs 26.5%, p = 0.001
---Hypotension 16% vs 3.5%, p <0.001
---Use of nasal canula oxygen 3% vs 0%, p < 0.01
The addition of diphenhydramine may not be necessary to prevent EPS in patients receiving haloperidol for agitation and is associated with increased length of stay and adverse events, likely due to its additive sedative properties.
Jeffers T, et al. Efficacy of combination haloperidol, lorazepam, and diphenhydramine vs. combination haloperidol and lorazepam in the treatment of acute agitation: a multicenter retrospective cohort study. J Emerg Med. 2022 Mar 11;S0736-4679(22)00057-9. doi: 10.1016/j.jemergmed.2022.01.009