Journal Article Annotations
2024, 4th Quarter

Catatonia and Delirium

Annotations by Sam Kohrman, MD and Laura Duque, MD
January, 2025

Zolpidem for the Management of Catatonia: A Systematic Review.
Catatonia Associated with Hyperthyroidism: An Illustrative Case and Systematic Review of Published Cases.

PUBLICATION #1 — Catatonia and Delirium

Zolpidem for the Management of Catatonia: A Systematic Review.

Matthew Gunther, Nathan Tran, Shixie Jiang.

Abstract: J Acad Consult Liaison Psychiatry 2024 Nov 9:S2667-2960(24)00114-9. doi: 10.1016/j.jaclp.2024.10.004. Online ahead of print.

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:
This systematic review explores the role of zolpidem in treating catatonia, reporting an overall positive response rate of 80% based on data from 35 case reports and series, without contributions from higher-quality studies like randomized trials. Zolpidem was effective in 91% (10/11 cases) as a diagnostic challenge agent, 100% (3/3 cases) as first-line monotherapy, 57% (4/7 cases) in first-line combination therapy, 70% (7/10 cases) as a second-line monotherapy, and 100% (4/4 cases) in second-line augmentation therapy. Doses ranged from 5 mg to 45 mg per day. These results suggest zolpidem may be a viable option when standard treatments such as benzodiazepines or ECT are ineffective or unavailable.

Strength and weaknesses:
The study’s reliance on case-level data limits the strength of its conclusions due to the absence of controlled trials, potential reporting bias, and lack of standardized protocols for zolpidem dosing or outcome assessment.

Relevance:
For CL psychiatrists, these findings offer significant practical value by highlighting an alternative therapeutic approach for catatonia in situations where first-line treatments fail or are inaccessible. The review draws attention to zolpidem as an underexplored option, emphasizing the need for further research to substantiate its role and ensure its safe and effective use in clinical practice.

PUBLICATION #2 — Catatonia and Delirium

Catatonia Associated with Hyperthyroidism: An Illustrative Case and Systematic Review of Published Cases.

Jeremy R Chaikind, Hannah L Pambianchi, Catherine Bledowski.

Abstract: J Acad Consult Liaison Psychiatry 28:S2667-2960(24)00119-8. doi: 10.1016/j.jaclp.2024.11.005. Online ahead of print.

Background:
Catatonia is a frequently missed diagnosis on medical wards, delaying effective treatment or permitting accidental use of neuroleptics that can exacerbate the condition. Thyroid storm has rarely been associated with catatonia in case reports, with no prior reviews synthesizing this research.

Objective:
We present a case of catatonia during thyroid storm following administration of low-dose haloperidol, followed by a review of previously published cases and discussion of their common factors and potential mechanisms.

Methods:
We first describe a case of a 37-year-old woman with untreated hyperthyroidism and bipolar disorder admitted for mania in the context of thyroid storm. She developed catatonic symptoms after receiving each of two doses of haloperidol. We then present a systematic review of the literature, drawn from the OVID Medline, PsycINFO, and Embase databases, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify case reports of catatonia presenting in association with hyperthyroidism.

Results:
Seventeen cases were identified-10 in published reports and seven in poster abstracts. The degree of evidence for catatonia varied, with few cases using formal scales. Several cases, including ours, reported recent administration of neuroleptics with dopamine antagonism (29%), usually at relatively low doses or with subsequent tolerance of neuroleptics when euthyroid. Other common factors included a history of psychiatric symptoms (41%) or presence of thyroid autoantibodies (41%).

Conclusions:
These results are consistent with clinical and preclinical evidence that hyperthyroidism might potentiate dopamine blockade, and they encourage clinicians to minimize neuroleptic use in this population. Other theories have also been proposed for catatonia’s association with hyperthyroidism, including direct thyrotoxic effect, autoimmune reaction, and mediation via another secondary psychiatric syndrome (e.g., mania). Clinicians should be aware of the potential for catatonia in thyroid storm, with or without neuroleptic use.

Annotation

The finding:
This systematic review, leading with a novel case report, spans the available literature on cases of catatonia amidst patients with hyperthyroidism, with a focus towards thyroid storm. Seventeen individual records were included in qualitative synthesis, 10 from case reports and seven from conference abstracts. From the findings, four potential mechanisms for development of catatonia in hyperthyroidism are proposed for consideration (neuroleptic induced catatonia with antipsychotic potentiation; direct thyroid hormone effect; autoimmune reaction; psychopathology mediation).

Strength and weaknesses:
This review offers a scope of the available literature surrounding catatonia in the setting of hyperthyroidism and thyroid storm. The quality of evidence remains low. The review’s reliance on case-level data limits the strength of its conclusions. Among these cases, the diagnosis of catatonia was heterogeneously reported and often uncertain, with few using standardized rating scales. Publication and reporting bias remains an issue.

Relevance:
As per the available literature, catatonia in the setting of hyperthyroidism is rare, yet occurs often enough to merit clinical attention for a CL psychiatrist. Further investigation and evidence are merited. The clinical takeaways are (a) to maintain a high index of suspicion for catatonia in cases of hyperthyroidism, particularly in a general hospital setting, and (b) in cases of such clinical suspicion to maintain a very low threshold to perform a catatonia exam and complete a standardized rating scale such as the Bush-Francis Catatonia Rating Scale (BFCRS) or the Northoff Catatonia Rating Scale (NCRS). It is reasonable to limit neuroleptics in these cases of catatonia amongst medically ill patients in the general hospital setting.