Emergence of a New Threat in East Asia: Severe Agitation and Suicide Attempts Linked to Etomidate-Infused E-Cigarettes
Journal
Asia-Pacific Psychiatry : official journal of the Pacific Rim College of Psychiatrists
Journal Volume
17
Journal Issue
1
Start Page
e70001
ISSN
1758-5864
Date Issued
2025-03
Author(s)
Abstract
Etomidate can induce psychiatric symptoms primarily by affecting GABA-𝐴 receptors, which are key inhibitory receptors in the brain (Forman 2011). These receptors regulate neuronal excitability by allowing chloride ions to flow, stabilizing neurons and suppressing excessive brain activity. Electroencephalographic studies indicate its disinhibitory effect on cortical function, and low GABA levels are linked to increased impulsivity (Li et al. 2020). Misuse of etomidate, particularly in e-cigarettes, has surged recently, leading to its classification as a controlled substance in South Korea, China, and Taiwan between 2020 and 2024. This misuse has been associated with severe adverse effects, including adrenal suppression and psychiatric symptoms like agitation and suicide attempts, which are underreported (Uhm et al. 2024). A 19-year-old male was admitted to the emergency department following a suicide attempt by jumping from a balcony and threatening others with a knife, behaviors that occurred after using an e-cigarette with unknown substances. He presented with stable vital signs and hemodynamic status, along with symptoms of tremors and drowsiness. However, he was only mildly dysphoric during the psychiatric evaluation and denied any hallucinations or delusions. A urine drug screen was negative for substances, including cocaine, opiates, marijuana, amphetamines, and barbiturates, and he was discharged once his mood stabilized. The patient had a history of substance use, beginning with ketamine and marijuana at age 16, which led to a moderate substance use diagnosis and subsequent rehabilitation with bupropion, which he did not adhere to. Despite this history, he had been abstinent for 3 months during military service with no significant psychiatric symptoms. Two weeks post-discharge, he resumed e-cigarette use and experienced tremors, a motorcycle accident, and aggressive behavior towards police within hours of use. He was admitted approximately 15 h after use. Routine lab tests showed mild hypokalemia, and urine drug screens were unremarkable. Psychiatric evaluation revealed mild irritability, and he was stable and cooperative after 7 h of observation before discharge. Given the absence of clear triggers and his history, further analysis identified etomidate acid, a metabolite of etomidate, in urine samples from both visits. The diagnosis was revised to etomidate intoxication, with detailed assessments and concentration levels presented in Table 1. This case report examines the acute effects of etomidate-infused e-cigarettes, highlighting their psychiatric impact. Previous cases showed hypokalemia, hypertension, and adrenocortical suppression in patients using etomidate-infused e-cigarettes, with symptoms resolving after discontinuation (Wu et al. 2024). At clinically relevant concentrations, etomidate acts as a positive modulator on GABA-𝐴 receptors, meaning it enhances the receptor's response to GABA, the primary inhibitory neurotransmitter (Tomlin et al. 1998). This enhancement reduces neuronal excitability by increasing the duration of inhibitory signals and slowing down their decay. By strengthening this inhibition, etomidate disrupts the balance of excitatory and inhibitory signals in the brain, potentially leading to altered consciousness and psychiatric symptoms. At higher, supraclinical concentrations, etomidate can directly activate GABA-𝐴 receptors without needing GABA itself (Rüsch et al. 2004). This “GABA-mimetic” action further stabilizes the open state of the receptor, prolonging inhibition beyond normal levels, which can impair normal neuronal communication and contribute to symptoms like drowsiness, confusion, and more severe psychiatric effects. The current case reveals that etomidate inhalation can induce psychiatric symptoms such as depressed mood, mood swings, and increased impulsivity, leading to suicide attempts and aggression. The short half-life of etomidate means symptoms resolve quickly but reappear with re-use, posing significant risks. The psychiatric effects, potentially due to GABA-A agonism causing disinhibition (Paton 2002), are not fully documented. Etomidate's potential for agitation is noted in surgical contexts, and its misuse in e-cigarettes exacerbates health hazards. For example, several police officers in Taiwan were killed by a driver under etomidate's influence. After China regulated etomidate at the end of 2023, 21 000 new users were identified within 3 months (Embassy of the People's Republic of China in the United States of America 2024), underscoring the urgent need for further research on its psychiatric effects. This case report involves a single patient case. According to the guidelines of the National Taiwan University Hospital Human Research Protection Center, case reports of one or two cases derived from routine medical procedures do not constitute human subject research and therefore do not require Institutional Review Board (IRB) review. The report adheres to the principles of the Declaration of Helsinki. The patient was an emergency department visitor who had only two visits to our hospital and has not returned for follow-up. Due to the difficulty in contacting the patient, it was not possible to obtain written informed consent. However, we have taken meticulous steps to de-identify the patient's information throughout the report to ensure the protection of the patient's privacy and rights. The authors declare no conflicts of interest. Data available on request due to privacy/ethical restrictions. The data that support the findings of this case report are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Subjects
agitation
etomidate
e‐cigarettes
suicide
Type
letter