Effects of Intravenous Hydroxyzine Versus Haloperidol Monotherapy for Delirium: A Retrospective Study

Kaoruhiko Kubo, MD; Moe Takehara; Mayuko Hirata; Sunjun Huh; Sayoko Kawano, PhD; Hiroyuki Uchida, MD, PhD; Hiroyoshi Takeuchi, MD, PhD

J Clin Psychiatry. 2025;86(1):24m15569

Abstract

Objective: Although antipsychotics are used commonly for delirium, they increase the risk of mortality in elderly patients and those with dementia. As hydroxyzine has sedative and anxiolytic effects, it can be used in the treatment of delirium. We performed a retrospective study to compare the effects of intravenous hydroxyzine and haloperidol monotherapy on delirium.

Methods: Patients who admitted to a university hospital from April 1, 2017, to September 30, 2022, and received either hydroxyzine or haloperidol intravenously as monotherapy for the treatment of delirium were included. The time to and rate of delirium improvement were compared. Improvement of delirium was defined as negative on the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM-ICU) for 3 consecutive days.

Results: Among 5,555 patients who developed delirium, 71 (1.3%) and 82 (1.5%) received intravenous hydroxyzine and haloperidol monotherapy, respectively. The time to delirium improvement was 7.0 days (95% CI, 5.7–8.3 days) for hydroxyzine and 8.2 days (95% CI, 7.6–8.8 days) for haloperidol, with no significant difference between the two groups (P = .059). On the other hand, the rate of delirium improvement was 23.9% for hydroxyzine and 8.5% for haloperidol, with a significant difference in favor of the hydroxyzine group (P = .009).

Conclusions: We first showed that intravenous hydroxyzine monotherapy was not inferior for the time to delirium improvement and superior for the rate of delirium improvement to intravenous haloperidol monotherapy. Considering that hydroxyzine is relatively safe with few side effects, it can be a viable option for delirium as an alternative to antipsychotics.

J Clin Psychiatry 2025;86(1):24m15569

Author affiliations are listed at the end of this article.

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