Clinical Summary: Effects of Intravenous Hydroxyzine Versus Haloperidol Monotherapy for Delirium: A Retrospective Study
Delirium is common in hospitalized older adults, and the standard pharmacologic fallback—antipsychotics—carries risks that matter most in the very patients who often need treatment, including extrapyramidal symptoms, QT prolongation, and increased mortality in elderly patients and those with dementia. This study asks a practical inpatient question: when oral treatment is not feasible, can intravenous hydroxyzine perform as well as or better than intravenous haloperidol for delirium?
Key Findings
- The rate of delirium improvement was 23.9% (n = 17) with hydroxyzine versus 8.5% (n = 7) with haloperidol, a significant difference favoring hydroxyzine (P = .009).
- Time to delirium improvement was 7.0 days (95% CI, 5.7–8.3 days) with hydroxyzine versus 8.2 days (95% CI, 7.6–8.8 days) with haloperidol; the log-rank comparison did not reach significance (P = .059).
- In Cox regression adjusted for age and sex, the hazard ratio for time to delirium improvement was 0.45 (95% CI, 0.18–1.11), with no significant difference between groups (P = .081).
- After excluding patients who switched to oral drugs due to resumption of eating and drinking, delirium improvement remained higher with hydroxyzine at 33.3% (n=17) versus 10.0% (n=7) with haloperidol (P=.001).
- In the additional analysis excluding route-switch cases, time to delirium improvement was 6.5 days (95% CI, 5.2–7.8 days) with hydroxyzine versus 8.1 days (95% CI, 7.4–8.8 days) with haloperidol, with P =.055.
For hospitalized patients receiving intravenous monotherapy for delirium, hydroxyzine produced a higher delirium improvement rate than haloperidol, while time to improvement was similar in the primary analysis. Intravenous hydroxyzine is a reasonable alternative when clinicians want to avoid dopamine D2 blockade.
Practice Implications
- When oral administration is difficult, consider intravenous hydroxyzine as an alternative to intravenous haloperidol for delirium, especially in older adults in whom extrapyramidal symptoms or other antipsychotic adverse effects are a concern.
- Expect the comparative benefit to be strongest for overall improvement rates: 23.9% versus 8.5% in the main analysis and 33.3% versus 10.0% after excluding route-switch cases.
- Interpret time-to-response cautiously: hydroxyzine was numerically faster at 7.0 days versus 8.2 days, but this difference was not statistically significant in the primary analysis (P = .059; hazard ratio 0.45 [95% CI, 0.18–1.11], P = .081).
- Apply these results mainly to a narrow monotherapy population, since only 71 (1.3%) hydroxyzine-treated patients and 82 (1.5%) haloperidol-treated patients met eligibility criteria among 5,555 patients who developed delirium.
