Key Takeaways
Extended Takeaways
- This analysis focused on a highly selected monotherapy cohort: only 71 (1.3%) hydroxyzine-treated patients and 82 (1.5%) haloperidol-treated patients met eligibility criteria out of 5,555 patients who developed delirium, so these findings apply most directly when other delirium agents are not being given concurrently.
- Among included patients, mean first-day doses were 29.9 mg/d for hydroxyzine and 3.3 mg/d for haloperidol, and mean maximum doses were 36.1 mg/d and 4.1 mg/d, respectively; these figures provide a practical sense of how intravenous monotherapy was actually used in hospital care.
- The main time-to-improvement analysis favored hydroxyzine numerically but did not reach significance by either method tested, with 7.0 days (95% CI, 5.7–8.3 days) versus 8.2 days (95% CI, 7.6–8.8 days) on Kaplan-Meier analysis, P = .059, and a Cox regression hazard ratio of 0.45 (95% CI, 0.18–1.11), P = .081.
- When patients who switched to oral drugs after resuming eating and drinking were excluded, hydroxyzine retained a higher improvement rate at 33.3% (n=17) versus 10.0% (n=7), P=.001, suggesting the signal was not explained only by route-of-administration changes during recovery.
- Prescribing patterns changed markedly over the study period, with hydroxyzine used in approximately 90% of cases after 2021 and haloperidol used in approximately 90% of cases before 2021; clinicians should interpret comparative effectiveness in light of this era effect and the institutional delirium algorithm.
- For older adults in whom dopamine D2 blockade is a concern, the paper highlights that hydroxyzine 30 mg occupied approximately 70% of histamine H1 receptors and cites very low muscarinic affinity values of >10,000, 3,800, and 4,600, supporting a plausible sedative mechanism without strong anticholinergic binding.
