Journal Article Annotations
2025, 2nd Quarter

Catatonia

Annotations by Samuel Kohrman, MD
July, 2025

Electrographic Features of Catatonia With or Without Comorbid Delirium.
Catatonia related to tacrolimus: a real world pharmacovigilance study of FDA adverse event reporting system (FAERS) database.

PUBLICATION #1 — Catatonia

Electrographic Features of Catatonia With or Without Comorbid Delirium.

James Luccarelli, Joshua R Smith, Niels Turley, Jonathan P Rogers, Haoqi Sun, Samuel I Kohrman, Gregory Fricchione, M Brandon Westover.

Abstract: J Neuropsychiatry Clin Neurosci. 2025 Jun 13:appineuropsych20240215. doi: 10.1176/appi.neuropsych.20240215. Online ahead of print.

Objective:
Catatonia is an underdiagnosed disorder characterized by speech and motor abnormalities. EEG examinations may improve the accuracy of a catatonia diagnosis, but clinical and electrographic correlations have not been established. The authors describe catatonic features and EEG findings in a large multisite retrospective cohort.

Methods:
The clinical records in two health care systems were searched for patients with an EEG recording and a catatonia assessment with the Bush-Francis Catatonia Rating Scale conducted within 24 hours of each other. Included patients were retrospectively screened for delirium through a chart-based assessment. Augmented inverse propensity weighting (AIPW) was used to estimate the causal effects of delirium and catatonia on the presence of an abnormal EEG finding.

Results:
Overall, 178 patients met inclusion criteria, 144 (81%) of whom had catatonia. Among the patients with catatonia, 43% also had delirium. EEG abnormalities were present among 43% of patients with catatonia, including 28% of patients with catatonia without delirium and 69% of the patients with co-occurring catatonia and delirium. Individual catatonic signs and EEG abnormalities showed only a weak correlation. In AIPW models, a delirium diagnosis was associated with significantly higher odds for an abnormal EEG finding (OR=6.75; 95% CI=2.83-16.14), whereas a diagnosis of catatonia was not (OR=1.83, 95% CI=0.79-4.24).

Conclusions:
EEG abnormalities are common among individuals with catatonia, but these are difficult to disentangle from abnormalities resulting from co-occurring delirium. Further research is needed to define the role of EEG examinations in the assessments of catatonia and delirium.

Keywords:
Catatonia; Delirium; Diagnosis and Classification in Neuropsychiatry; EEG.

Annotation

The finding:
This multisite cohort study of general hospital inpatients with an EEG recording and a catatonia clinical examination (BFCRS) within 24 hours included 178 patients between two academic medical centers in the US. Catatonia was defined as ≥ 4 items on the Bush Francis Catatonia Screening Instrument (the first 14 items on the BFCRS); 144 out of 178 patients with (81%) met criteria. Delirium was determined by the CHART-DEL tool (a validated tool for retrospective chart review for delirium with a sensitivity of 0.74 and specificity of 0.83). 72 of 178 patients (40%) met CHART-DEL criteria, 10 of whom did not meet criteria for catatonia. 43% of patients with catatonia had an EEG abnormality. EEG abnormalities were more common among catatonic patients with delirium than among those without (69% vs. 28%). 61% (N=36 of 59) of patients with catatonia and a primary general medical diagnosis had an abnormal EEG finding, compared with 35% (N=30 of 85) of patients with catatonia and a primary psychiatric diagnosis. A diagnosis of delirium was associated with significantly higher odds of an abnormal EEG finding but a catatonia diagnosis was not associated with significantly higher odds of an abnormal EEG. There was only a weak correlation between individual BFCRS signs and specific EEG abnormalities.

Strength and weaknesses:
This is the largest study of visually described EEG findings in catatonia published to date. Strengths include a large sample size, a multicenter design, use of standardized nomenclature for reporting EEG features, and assessment for both delirium and catatonia at time of EEG recording. Weaknesses include retrospective observational study design, and classifications for both catatonia and delirium that have not been rigorously studied in this specific patient population of comorbid neuropsychiatric dysfunctions of both delirium and catatonia in a general hospital setting.

Relevance:
Overall, these results suggest that the two disorders (catatonia and delirium) frequently co-occur and that patients with both disorders may differ clinically from those with either disorder alone. This appears consistent with what is encountered in clinical practice in the general hospital setting. Certainly, further research is warranted to better characterize the extent of this overlap between catatonia and delirium. Further research is indicated to determine whether optimal treatment for catatonia should differ depending on the presence of comorbid delirium, and if so, how treatment should differ.

PUBLICATION #2 — Catatonia

Catatonia related to tacrolimus: a real world pharmacovigilance study of FDA adverse event reporting system (FAERS) database.

Jing Yang, Hui Yang, Zhuoling An.

Abstract: Expert Opin Drug Saf. 2025 May;24(5):595-598. doi: 10.1080/14740338.2024.2393757. Epub 2024 Aug 21.

Background:
Emerging case reports have highlighted that catatonia may be a complication that is easily misdiagnosed. Our study aimed to summarize the clinical characteristics of patients with tacrolimus-induced catatonia and assess the association between tacrolimus and catatonia through disproportionality analysis.

Research design and methods:
We conducted a retrospective pharmacovigilance study using the FAERS database, analyzing data up to the third quarter of 2023. The clinical characteristics of the reported cases were summarized using descriptive statistics. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between tacrolimus and catatonia.

Results:
There were 66 reports of tacrolimus-related catatonia, with the majority of cases occurring in the United States (78.79%). The risk signal for tacrolimus-related catatonia was significantly higher compared to all other drugs (ROR 3.222 [2.524, 4.111], IC 1.632 [1.273, 1.991]). A significant association was detected in both male and female, while the risk signal of tacrolimus-associated catatonia was only found in the subgroups aged over 40 years.

Conclusions:
Our study identified a safety signal for the association between tacrolimus and catatonia compared to all other drugs in FAERS database, particularly in patients aged 40 and above.

Keywords:
Catatonia; FAERS database; adverse event; pharmacovigilance; tacrolimus.

Annotation

The finding:
In this retrospective pharmacovigilance study of the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, comprised of voluntarily submitted Adverse Event Reports to the FDA from 2004-2023, Adverse Events (AEs) were coded based on preferred term codes from the Medical Dictionary for Regulatory Activities. Tacrolimus (Envarsus XR, Prograf and Protopic) was the target drug and investigated AEs included catatonia, malignant catatonia and withdrawal catatonia. Out of 76,175 reported AEs, 66 reports of tacrolimus-related catatonia were identified; 51 cases were reported from the United States. 88.3% of the cases resulted in hospitalization. The risk signal for tacrolimus-related catatonia was significantly higher compared to all other drugs in the FAERS database, and separated significantly from fellow calcineurin inhibitor cyclosporine, which did not have a significant risk signal. The risk signal for tacrolimus associated catatonia was found only in the subgroups aged over 40 years.

Strength and weaknesses:
Strengths include a notably large sample size. This appears to be the first study searching a database for a correlation between tacrolimus and catatonia. Here tacrolimus is compared against other pharmacologic agents including cyclosporine. The observational study design is one limitation; these findings are fraught with bias including but not limited to selection bias and reporting bias.

Relevance:
This comparative correlative finding of tacrolimus’s significantly higher association with catatonia as compared to other agents including fellow calcineurin inhibitor cyclosporine suggests the importance of vigilance and early monitoring for catatonia in patients on tacrolimus over age of 40 for neurotoxicity including catatonia, particularly given risk for co-occurring delirium in such a vulnerable (likely post-transplant) population. Further research is warranted.