Journal Article Annotations
2025, 1st Quarter

Catatonia

Annotations by Samuel Kohrman, MD
March, 2025

The Population-Based Incidence and Prevalence of Catatonia.
Zolpidem for the Management of Catatonia: A Systematic Review.

PUBLICATION #1 — Catatonia

The Population-Based Incidence and Prevalence of Catatonia.

James Luccarelli, Joshua R Smith, Mark Kalinich, Ali Amad, Jonathan P Rogers.

Abstract: J Neuropsychiatry Clin Neurosci. 2025 Jan 10:appineuropsych20240072. doi: 10.1176/appi.neuropsych.20240072. Online ahead of print.

Objective:
Catatonia is a neuropsychiatric disorder that is associated with a range of medical and psychiatric illnesses. Although many single-center studies have been conducted, uncertainty over the population-based incidence and prevalence of the disorder remains. This study reports on the incidence and prevalence rates of catatonia extrapolated from two large epidemiologic studies in the United Kingdom and United States.

Methods:
Incidence rates (defined as the number of catatonic episodes per 100,000 person-years) and prevalence rates (defined as the proportion of individuals with catatonia in a given year) were calculated from the two studies.

Results:
U.K. data showed an incidence of 4.34 (95% CI=3.98-4.72) catatonic episodes per 100,000 person-years with an average 1-year prevalence of 4.39 (95% CI=4.03-4.77) catatonic episodes per 100,000 persons. U.S. data revealed a 1-year prevalence of 5.15 (95% CI=5.08-5.23) catatonia-related hospitalizations per 100,000 persons.

Conclusions:
Catatonia is a rare disorder, qualifying as an orphan disease under both European Medicines Agency and U.S. Food and Drug Administration criteria. Further research is needed to rigorously define the epidemiology of catatonia in other populations.

Keywords:
Catatonia; Epidemiology; Incidence; Neuropsychiatric disorders; Prevalence.

Annotation

The finding:
Incidence of catatonia in the U.K. sample (retrospective chart review) was defined as new cases of DSM-5-TR catatonia during the study period (2007-2016), treating each episode separately. In this sample, there were 539 catatonic episodes among 373 individuals from 12,420,547 person-years of follow-up, representing an incidence rate of 4.34 (95% CI=3.98–4.72) catatonic episodes per 100,000 person-years. Prevalence was defined for this sample as the number of unique individuals experiencing catatonia within a regional population during a 1-year time period; 545 total catatonic episodes were recorded, for an average 1-year prevalence of 4.39 (95% CI=4.03–4.77) catatonic episodes per 100,000 persons. The U.S. sample incidence and prevalence was extrapolated from the American Hospital Association [AHA] 2020 survey based on individual ICD code charges F06.1 or F20.2 (from 33,356,853 admissions to 6,093 hospitals) and the U.S. Census population in 2020 (331,449,281). This AHA survey identified 16,575 catatonia hospitalizations in the United States in 2020, with an overall hospitalization rate involving catatonia of 0.05%. Extrapolating this observation to all hospitalizations in the US from the 2020 AHA data, this rate represents 17,079 catatonia- related hospitalizations in a U.S. population of 331,449,281, for a 1-year prevalence rate of 5.15 (95% CI=5.08–5.23) catatonia-related hospitalizations per 100,000 persons.

Strength and weaknesses:
Strengths of this study include its two large population-based samples spanning two countries, using different methods (chart review vs administrative claims), resulting in strikingly similar epidemiologic findings. Limitations are the observational, retrospective study design, the inability to monitor for accuracy in coding or diagnosis and inability to factor in bias of potential over or under diagnosis of catatonia. Further limitations are the difficulty in comparing these results to other meta-analysis results from smaller studies examining psychiatric inpatients in general.

Relevance:
This large and novel review of incidence and prevalence of catatonia across general hospital and inpatient psychiatry settings across two countries and databases is a helpful addition to the literature, indicating similar prevalence rates per 100,000 persons, and that catatonia is a rare disorder with a short duration.

PUBLICATION #2 — Catatonia

Zolpidem for the Management of Catatonia: A Systematic Review.

Matthew Gunther, Nathan Tran, Shixie Jiang.

Abstract: J Acad Consult Liaison Psychiatry. 2025 Jan-Feb;66(1):49-56. doi: 10.1016/j.jaclp.2024.10.004. Epub 2024 Nov 9.

Background:
Catatonia is a psychomotor syndrome associated with neurotransmitter disturbances, common in both psychiatric and medical settings. Hypoactivity of the GABA_A receptor is one of the predominant theories behind the pathophysiology of catatonia, affecting both motor functioning and emotional regulation. Benzodiazepines such as lorazepam are considered the first-line treatment for catatonia. However, up to 27% of catatonia cases fail to respond to benzodiazepines alone. Zolpidem, which can be used as a challenge, monotherapy, or augmentation agent, serves as a promising pharmacological agent for catatonia due to its unique pharmacodynamic and pharmacokinetic profile.

Objective:
We sought to systematically examine the evidence behind zolpidem’s use among adult patients to understand its clinical utility in the management of catatonia against prevailing treatments such as lorazepam and electroconvulsive therapy.

Methods:
We conducted a systematic review using search terms related to zolpidem and catatonia in PubMed, EMBASE, and Web of Science. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 29 studies, including case studies and case series that met inclusion criteria.

Results:
We reviewed 35 cases in which zolpidem was used for catatonia management (age: mean = 51.5 ± 21.0 standard deviation years; 68.6% female; Bush Francis Catatonia Rating Scale: mean = 22.2 ± 9.0 standard deviation). Proportions of positive responses for zolpidem on catatonia varied by treatment approach: 91% as a challenge agent (n = 10), 100% as a first-line monotherapy agent (n = 3), 57% as a first-line combination therapy agent (n = 4), 70% as a second-line monotherapy agent (n = 7), and 100% as a second-line augmentation agent (n = 4). In total, 28 out of the 35 reported cases of catatonia (80%) responded positively to zolpidem.

Conclusions:
An 80% positive response rate for zolpidem in lysing catatonia is encouraging but may be an overestimate due to reporting bias of case-level data. Results may be explained by zolpidem’s selectivity for the α₁ subunit of the GABA_A receptor. Thus, zolpidem may be an underutilized catatonia treatment and prove useful in situations when benzodiazepines fail or when electroconvulsive therapy access is limited. Given that current literature on the use of zolpidem for catatonia is limited to case reports, more robust research in this area is warranted.

Keywords:
GABA(A) receptor; alpha-1 subunit; benzodiazepines; catatonia; lorazepam; zolpidem.

Annotation

The finding:
29 studies were included, resulting in 25 case reports and 4 case series for a total of 35 individual cases, 80% of which (n= 28 of 25) responded to zolpidem as treatment for catatonia via a decreased Bush Francis Catatonia Rating Score or via review of the case; dosing ranged from 5mg to 45mg daily. Zolpidem use for catatonia was classified into 5 treatment groups with the following positive responses to treatment: [1] ‘challenge agent’ (n=10 of 11, 91%, dose 5-10mg), [2] ‘first-line monotherapy agent’ (n=3 of 3, 100%, dose 10mg daily to 7.5mg every 4 hours), [3] ‘first-line combination therapy agent’ (n=4 of 7, 57%, dose 5 mg nightly to 30 mg daily), [4] ‘second-line monotherapy agent’ (n=7 of 10, 70%, dose 10mg four times daily), or [5] ‘second-line augmentation agent’ (n=4 of 4 100%, dose 4mg twice daily to 10mg three times daily). All seven cases of unsuccessful zolpidem response were of catatonia from a primary psychiatric etiology.

Strength and weaknesses:
Strengths include focusing specifically on cases of zolpidem used to treat catatonia, with rigorous inclusion/exclusion criteria for the study type, and a thoughtful classification of treatment strategies. Consideration is given to the unique pharmacologic profile of zolpidem at the GABA A a1 subunit. Weaknesses include case-level data with heterogeneity in etiology of catatonia as well as in description of catatonic symptoms and diagnoses (with or without Bush Francis Catatonia Rating Scales). This study lacks a control group and likely overestimates treatment response via reporting bias. Duration of dosing and time to response were both not consistently reported.

Relevance:
This is the first extensive systematic review examining the efficacy of zolpidem in catatonia management. It provides promising case-level data for its use in the armamentarium of catatonia treatment, with further investigation warranted.