Journal Article Annotations
2024, 2nd Quarter

Catatonia and Delirium

Annotations by Samuel Kohrman, MD
July, 2024

Antipsychotics in the Treatment of Delirium in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Generalized Periodic Discharges Associated With Catatonia and Delirium: A Case Series.

PUBLICATION #1 — Catatonia and Delirium

Antipsychotics in the Treatment of Delirium in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Kallirroi Laiya Carayannopoulos, Fayez Alshamsi, Dipayan Chaudhuri, Laura Spatafora, Joshua Piticaru, Kaitryn Campbell, Waleed Alhazzani, Kimberley Lewis.

Abstract: Crit Care Med. 2024 Jul 1;52(7):1087-1096. doi: 10.1097/CCM.0000000000006251. Epub 2024 Mar 15.

Objectives:
To conduct a systematic review and meta-analysis assessing whether the use of antipsychotic medications in critically ill adult patients with delirium impacts patient-important outcomes.

Data sources:
A medical librarian searched Ovid MEDLINE, EMBASE, APA PsycInfo, and Wiley’s Cochrane Library as well as clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2023.

Study selection:
Independently and in duplicate, reviewers screened abstracts and titles for eligibility, then full text of qualifying studies. We included parallel-group randomized controlled trials (RCTs) that included critically ill adult patients with delirium. The intervention group was required to receive antipsychotic medications at any dose, whereas the control group received usual care or placebo.

Data extraction:
Reviewers extracted data independently and in duplicate using a piloted abstraction form. Statistical analyses were conducted using RevMan software (version 5.4).

Data synthesis:
Five RCTs ( n = 1750) met eligibility criteria. The use of antipsychotic medications compared with placebo did not increase the number of delirium- or coma-free days (mean difference 0.90 d; 95% CI, -0.32 to 2.12; moderate certainty), nor did it result in a difference in mortality, duration of mechanical ventilation, ICU, or hospital length of stay. The use of antipsychotics did not result in an increased risk of adverse events (risk ratio 1.27; 95% CI, 0.71-2.30; high certainty). Subgroup analysis of typical versus atypical antipsychotics did not identify any subgroup effect for any outcome.

Conclusions:
In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in delirium- or coma-free days when delirious critically ill adults are treated with antipsychotic medications. Further studies in the subset of patients with hyperactive delirium may be of benefit.

Annotation

The finding:
In critically ill adults in the intensive care unit (ICU), who screened positive for delirium via the Confusion Assessment Method for the ICU (CAM ICU) or Intensive Care Delirium Screening Checklist (ICDSC), the scheduled administration of antipsychotics (haloperidol in 5mg doses to a maximum of 15-30mg daily, quetiapine to a maximum of 200-300mg daily, and ziprasidone ranging from 5mg to 40mg total daily dose) as compared to standard treatment or placebo, resulted in no difference in delirium or coma free days, in mortality at 28 days, in duration of mechanical ventilation, or in ICU or hospital length of stay. Such administration did not result in increased risk of adverse events as compared to standard treatment or placebo. Findings were determined to have moderate levels of certainty.

Strength and weaknesses:
Strengths for this systematic review and meta-analysis include a methodologically rigorous process with a large sample size for this population (1750 patients across 5 studies), a range of antipsychotic treatments (haloperidol, quetiapine and ziprasidone), and a mix of hyperactive (33%) and hypoactive (67%) delirium. Limitations include narrower scope of patients to the ICU setting, and inability to discern via subgroup analysis a difference between hyperactive and hypoactive delirium. Longer term risk evaluation was not available.

Relevance:
These findings, which look at antipsychotics exclusively as a treatment modality for delirium, suggest that in a population of critically ill adult patients in the ICU who screen positive for delirium via the CAM ICU or ICDSC, based on the study metrics, the scheduled antipsychotic dosing as detailed above does not statistically lend to more acute harm than not or to more acute benefit than not. It does not account for decrease in delirium intensity, symptomatic relief, patient comfort, ease of care provision. Similarly, it doesn’t account for risk of mortality beyond 28 days or for other longer-term risks. Decisions to use antipsychotics in this population, as per this paper, remain based on clinical judgement in each individual case.

PUBLICATION #2 — Catatonia and Delirium

Generalized Periodic Discharges Associated With Catatonia and Delirium: A Case Series.

James Luccarelli, Joshua R Smith, Gregory Fricchione, M Brandon Westover.

Abstract: J Neuropsychiatry Clin Neurosci. 2024 May 9:appineuropsych20230174. doi: 10.1176/appi.neuropsych.20230174. Online ahead of print.

Objective:
Generalized periodic discharges are a repeated and generalized electroencephalography (EEG) pattern that can be seen in the context of altered mental status. This article describes a series of five individuals with generalized periodic discharges who demonstrated signs and symptoms of catatonia, a treatable neuropsychiatric condition.

Methods:
Inpatients with a clinical diagnosis of catatonia, determined with the Bush-Francis Catatonia Rating Scale (BFCRS), and EEG recordings with generalized periodic discharges were analyzed in a retrospective case series.

Results:
Five patients with catatonia and generalized periodic discharges on EEG were evaluated from among 106 patients with catatonia and contemporaneous EEG measurements. Four of these patients showed an improvement in catatonia severity when treated with benzodiazepines, with an average reduction of 6.75 points on the BFCRS.

Conclusions:
Among patients with generalized periodic discharges, catatonia should be considered, in the appropriate clinical context. Patients with generalized periodic discharges and catatonia may benefit from treatment with empiric trials of benzodiazepines.

Keywords:
Antiepileptic Drugs; Benzodiazepines; Case Series; Catatonia; Electroencephalography; Generalized Periodic Discharges

Annotation

The finding:
On retrospective medical record analysis at a large academic medical center, out of a sample of 106 identified inpatients between 2017 and 2022 with both an Electroencephalogram (EEG) and a scored Bush Francis Catatonia Exam (BFCE) completed within 24 hours of one another, five patients were found to have generalized periodic discharges on EEG. All five had clinical exams consistent with both catatonia and delirium. In this retrospective case series, four of five were treated with benzodiazepines and all four showed an improvement in BFCE (14 to 7; 24 to 19; 16 to 7; 21 to 15) on repeat exams after initiation of scheduled lorazepam (1mg q 6hours; 2mg q 6 hours; 0.25mg q 6 hours; 2mg q 4 hours).

Strength and weaknesses:
Strengths include introducing a novel finding in the literature, of the potential association of catatonia and generalized periodic discharges in the setting of delirium. Limitations include observational study design with lower evidence strength (retrospective case series), lack of follow-up EEG for some of the cases, and lack of clarity on if benzodiazepines were administered orally or parenterally in each case.

Relevance:
Catatonia and delirium do overlap in the general hospital and inpatient psychiatric settings; currently, catatonia, under DSM-5-TR criteria, cannot be diagnosed in the presence of delirium. This case series highlights the possible association of catatonia with general periodic discharges on EEG. This series suggests that empiric benzodiazepine treatment may clinically benefit patients with comorbid catatonia and generalized periodic discharges in the setting of delirium. Further investigation is warranted.