A Critical Reappraisal of Haloperidol for Delirium Management in the Intensive Care Unit: Perspective from Psychiatry

Abstract

Delirium is a complex neuropsychiatric syndrome with multifactorial pathophysiology, encompassing a wide range of neuropsychiatric symptoms, and its management remains a significant challenge in critical care. Although often managed with antipsychotics, like haloperidol, current research has predominantly focused on dopamine dysregulation as the primary driver of delirium, overlooking its broader neuroanatomical and neurochemical underpinnings. This has led to a majority of research focusing on haloperidol as a treatment for intensive care unit (ICU) delirium. Our review critically evaluates the role of haloperidol in ICU delirium management, particularly in light of recent large-scale randomized controlled trials (RCTs) that have primarily focused on delirium-free days and mortality as the primary endpoints. These studies highlight an limited understanding of the true nature of delirium treatment, which requires a broader, neuropsychiatric approach. We argue that future research should shift focus to neuropsychiatric symptoms such as agitation and psychosis and explore the clinical and functional benefits of reducing these distressing symptoms. Additionally, the stratification of delirium by subtypes and etiology, the enhancement of detection tools, and the adoption of multi-intervention and multi-disciplinary care approaches should be prioritized. Despite the methodological flaws in these studies, the findings support the safety of haloperidol in the ICU setting, with minimal risk of adverse events, particularly cardiac and neuropsychiatric. Moving forward, delirium research must integrate modern neuroscientific understanding and adopt more multi-disciplinary input and nuanced, patient-centered approaches to truly advance clinical care and outcomes.

Keywords: acute brain failure; antipsychotics; critical care; delirium; dopamine; encephalopathy; haloperidol; intensive care unit; psychopharmacology.

Figure 1

Brief overview of ICU delirium pathophysiology. Abbreviations: CNS = central nervous system; GABA = gamma-aminobutyric acid; BBB = blood–brain barrier.