Journal Article Annotations
2024, 3rd Quarter
Annotations by Samuel Kohrman, MD
October, 2024
Of interest:
The finding:
The analysis is based on claims data for catatonia diagnoses at time of discharge inclusive of any billed diagnosis during admission (F06.1 Catatonic disorder due to a known physiological condition; F20.2 Catatonic schizophrenia) within non-Federal acute care inpatient hospital settings. Among 174,776,205 recorded hospitalizations between 2016-2020, a total of 61,990 involved a diagnosis of catatonia. Significant differences between pediatric and adult cases were that pediatric cases were more likely to be male, less likely to be white, more likely to be discharged home versus to another facility. Comparatively between pediatric and adult cases, encephalitis was ten times as frequently diagnosed and neurodevelopmental disorders 31 times as frequently diagnosed. There is an elevated risk ratio of pediatric versus adult catatonia cases having diagnoses of Autism Spectrum Disorder, ADHD psychotic disorders, and of receiving physical restraints.
Strength and weaknesses:
Strengths include a very large sample size over a five-year period offering high powered findings. In addition to the retrospective observational study design, selection and sampling bias come in to play. Rather than tracking individual patients, individual hospital discharge events are tracked – as such the same patient could present for multiple hospitalizations in the five-year study period, potentially overrepresenting some findings. Catatonia was identified only if hospital charges were filed and captured for a catatonia diagnosis, perhaps underrepresenting the findings as a catatonia diagnosis may not be discretely billed for and thus captured. The sample is limited to general hospitals; freestanding psychiatric hospital were not included.
Relevance:
In this sample of general hospital catatonia cases, Autism Spectrum Disorder, ADHD and Autoimmune Encephalitis are more highly represented in pediatric than adult catatonia cases proportionally, and may be under-diagnosed and under-represented in adult cases. Such neurodevelopmental and neuroautoimmune conditions do predispose patients across the lifespan to neuropsychiatric sequelae including epilepsy and catatonia. It is reasonable to consider approaching otherwise relatively undifferentiated adult catatonia cases with a high index of suspicion for underlying concomitant neurodevelopmental disorders and encephalitis; doing so could influence more targeted and potentially more effective evaluation and treatment.
The finding:
This systematic review investigated catatonia in the setting of dementia via a systematic search of MEDLINE and EMBASE case reports and case series on human subjects in English, Portuguese, Italian, and Spanish published between January 1994 and March 2021. It included adult patients >/= 50 years old, catatonia based on clinical diagnosis or diagnoses using specific criteria. Additionally, malignant/lethal catatonia, NMS, periodic catatonia, and delirious mania were considered special forms of catatonia and were included. Dementia was defined as diagnosis of dementia or major neurocognitive disorder based on clinical diagnosis or diagnostic criteria. In all, 182 articles with 225 unique cases were included. Twenty-four cases were identified with catatonia and dementia, while 201 were identified with catatonia without dementia. No significant differences in clinical presentation of catatonia between patients with and without dementia. The majority of catatonia cases were hypokinetic with mutism, rigidity, immobility and negativism. Overall, treatment modalities were similar with the exception that patients with catatonia and dementia were more frequently treated with NMDA receptor antagonists memantine and/or amantadine than those without dementia. Of note, these agents were started after catatonia diagnosis in most cases rather than use as existing treatment for dementia. Patients with comorbid dementia demonstrated a lower complete response rate to treatment. Patients with catatonia and dementia demonstrated a lower rate of acute medical conditions than did patients with catatonia alone. Delirium accounted for 11% of acute medical condition inpatients without dementia.
Strength and weaknesses:
Strengths include the modality of article selection, as it allowed for more clinical precision in the analysis. The systematic review design helps improve somewhat an otherwise low level of evidence. Limitations include the article types chosen (only single case reports and case series). This limits epidemiological assertions; findings in this study can be interpreted as frequency reports only, rather than generalizable findings. This methodology introduces publication bias and a smaller comparative sample size for patients with concomitant dementia and catatonia.
Relevance:
Given the existing limited evidence base in literature describing catatonia in elderly patients and in patients with dementia, this nuanced review approach offers more clinical insights albeit with notable limitations. The descriptive findings in patients with dementia and catatonia (fewer acute medical conditions, more NMDA antagonist agents offered, similar rates of ECT and benzodiazepines utilized, and a lower symptomatic treatment response rate) indirectly suggest a potentially different biological mechanism in patients with dementia and catatonia vs aged matched patients with catatonia alone. Further representation of patients with coexisting catatonia and dementia is warranted in the literature for further evaluation, including prospective studies.
The finding:
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 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.
The finding:
This review is helpful for accumulating cases in the literature and presenting the current state of the evidence. There are significant limitations to this study, as the included cases carry significant heterogeneity in treatment modality including ketamine as the primary intervention (with variability in route of administration, dose, frequency and co-administered agents) and ketamine as an anaesthetic in ECT treatments. Moreso, treatment response was minimally described, with a Bush Francis Catatonia Exam finding present in only 7 of the 25 patients.
Given the limitations, this review does not offer adequate evidence to influence clinical management.
Entertaining the idea of ketamine treatment in the setting of catatonia is at this point unwarranted prior to utilizing existing evidence-based treatments. Utilizing ketamine clinically as a treatment for catatonia remains highly controversial and currently is not recommended.
One could conceptually consider ketamine as a theoretical treatment for catatonia likely in cases of catatonia secondary to depression (preferably unipolar, without psychotic features). Its use (even in non-catatonia cases, and especially in cases of catatonia) necessitates a profound abundance of caution, acknowledging that it could worsen mania, mixed states, psychosis, as well as increasing risk for seizure, delirium, arrhythmias, hypertension, stroke, among others.