Journal Article Annotations
2026, 1st Quarter
Critical Care
Annotations by Emma Torncello, MD and Natalie Fedotova, MD, PhD
March, 2026
PUBLICATION #1
Exposure to Antipsychotic Medication Is Associated With Less Days Alive and Free From Catatonia in Critically Ill Patients
Gloria Nashed Mina, Trey McGonigle, Jinyuan Liu, Nathan E Brummel, Mayur B Patel, Joshua R Smith, Pratik P Pandharipande, Robert S Dittus, E Wesley Ely, Jo Ellen Wilson
Abstract:
Objectives: Catatonia occurs in critical illness, however, underlying causal mechanisms are unknown. We aim to determine if exposure to antipsychotic medication is associated with less days alive and free from catatonia in critically ill adults.
Design: The Delirium and Catatonia Prospective Cohort Investigation is a prospective cohort.
Setting: Single academic medical center's medical, surgical, and trauma ICUs.
Patients: Critically ill adult patients on mechanical ventilation or vasopressors without a major neurocognitive disorder, severe psychiatric disorder, or catatonia at baseline.
Interventions: The primary exposure was antipsychotic administration and cumulative dosage during the first 5 and 14 days from enrollment.
Measurements and main results: Catatonia was evaluated with the Bush-Francis Catatonia Rating Scale mapped to Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition criteria. The primary outcome was catatonia-free days (CFDs), defined as the number of days the patient was alive and free from catatonia. Adjusted proportional odds logistic regression was used to estimate the odds ratio (OR) of outcome events. Patients ( n = 270) were enrolled with a median (interquartile range) age of 54.5 years (36.7-67.2 yr). Of patients who were exposed to antipsychotic medication ( n = 102), 27 (26%) experienced catatonia. Compared with patients who were never exposed to antipsychotics, those exposed in both the 5- and 14-day models had a 74% and 51% reduction in the odds of more CFD (OR, 0.2568; 95% CI, 0.1580-0.4173) and (OR, 0.4939; 95% CI, 0.3857-0.6325), respectively. Furthermore, those exposed to higher dosages had a 97% reduction in the odds of more CFD (OR, 0.0281; 95% CI, 0.0142-0.0556) and (OR, 0.0335; 95% CI, 0.0166-0.0673) compared with those exposed to lower dosages in both the 5- and 14-day models, respectively.
Conclusions: This study may influence how intensivists approach the use of antipsychotic medications and may build upon existing evidence that dopamine blockade is an underlying biologic mechanism underlying catatonia.
Keywords: antipsychotic agents; catatonia; coma; critical care; delirium.
Annotation
The finding: According to this single-center prospective observational cohort study, critically ill adults who received antipsychotics were more likely to develop catatonic symptoms compared to those who never received antipsychotics (26% vs. 7.1%, over 14 days, respectively). Higher cumulative exposure (≥ 123.1mg over 5 days or ≥ 343.7 over 14 days in haloperidol-equivalent dose) was associated with fewer days alive and free of catatonia (CFD). Haloperidol constituted 22% of exposures and the remainder was secondary to various atypical agents.
Strength and weaknesses:
In terms of strengths, the study took a prospective approach, utilized well-trained, blinded staff for daily assessments, and introduced a novel – albeit not yet validated – outcome measure (“catatonia free days” or CFD). The analysis included several covariates and demonstrated a dose-dependent relationship. Nonetheless, several factors limit interpretation. The exact timing of catatonic symptom onset was unclear with respect to antipsychotic exposure and, as the authors note, some patients may have been symptomatic on days prior to the first day of assessment. Further, early signs of psychomotor disturbance secondary to catatonia could have been interpreted as agitation and led to antipsychotic use; admittedly, this is an incomplete explanation as hypoactive features were more common. The antipsychotic-exposed group differed from the non-exposed group in several ways, including having a higher percentage of patients with delirium, coma, TBI, and mechanical ventilation, leaving much room for confounding. Thus, one interpretation is that patients with a higher burden of brain dysfunction were more likely to develop catatonia as well as symptoms prompting antipsychotic administration. Notably, the information regarding the specific indications for antipsychotic use, as well as co-exposure to other relevant pharmacological agents, was not available. Finally, the study excluded patients with significant psychiatric illness or dementia, who are more likely to be exposed to antipsychotics in the ICU and are more vulnerable to catatonia, limiting generalizability.
Relevance:
C-L psychiatrists have long emphasized taking a judicious approach to the use of antipsychotics in managing ICU delirium, with several trials failing to show benefits with indiscriminate administration (e.g., MIND-USA). This study builds on prior work highlighting the prevalence of catatonia in critically ill delirious patients (1) and raises the question of antipsychotic-induced symptoms. While the mechanism implicating dopamine blockade is plausible, further research is needed to clarify causal relationships and expand our understanding of pre-existing vulnerability. In the meantime, CL psychiatrists will continue taking an indication-specific, cautious approach to antipsychotic use in the ICU and delirium management, while carefully monitoring for the emergence of catatonic symptoms.
- Wilson JE, Carlson R, Duggan MC, Pandharipande P, Girard TD, Wang L, Thompson JL, Chandrasekhar R, Francis A, Nicolson SE, Dittus RS, Heckers S, Ely EW; Delirium and Catatonia (DeCat) Prospective Cohort Investigation. Delirium and Catatonia in Critically Ill Patients: The Delirium and Catatonia Prospective Cohort Investigation. Crit Care Med. 2017 Nov;45(11):1837-1844. doi: 10.1097/CCM.0000000000002642. PMID: 28841632; PMCID: PMC5678952.