(56) Bromazolam Withdrawal Requiring ICU Admission: Case Report of Designer Benzodiazepine Use

Background & Introduction: Benzodiazepines are commonly prescribed medications in the United States, and prescription benzodiazepine misuse is a well-established public health challenge. However, “designer” benzodiazepines represent a novel class of synthetic benzodiazepine compounds which may be easily obtained without a prescription.

Broadly speaking, designer benzodiazepines are a class of substances derived from currently or formerly licensed benzodiazepines through the process of structural modification. The resultant substances retain pharmacological effects similar to licensed benzodiazepines, but potency, half-life, and purity may vary significantly between designer products. Specific examples include 1,4-benzodiazepines (e.g., meclonazepam, phenazepam), triazolobenzodiazepines (e.g., bromazolam, nitrazolam), and thienotriazolobenzodiazepines (e.g., deschloroetizolam) (1,2).

These substances are most frequently purchased from online retailers, such as those on the dark web, and through websites identifying the compounds as research chemicals. Limitations in current testing methods may affect detection of designer benzodiazepines in clinical samples, but commercially available immunochemical assays do retain cross-reactivity with many current designer benzodiazepines (3).

Due to its psychoactive effects, ease of access, and potential difficulties with monitoring and detection, we present a case of bromazolam use complicated by withdrawal necessitating ICU-level care. This case will help facilitate further review and discussion of designer benzodiazepines for addiction medicine providers.

Case Description: This poster describes the case of a 22-year-old male with a history of cannabis and alcohol use who presented for emergency department evaluation with an initial complaint of chest pain. In this setting, vital signs were notable for tachycardia and hypertension. The patient reported to emergency department staff that he had been using bromazolam, a synthetic triazolobenzodiazepine purchased online, daily for at least the last three months. Collateral information from his parents confirmed the recent cessation of bromazolam use; his parents added concern for odd dreams and auditory hallucinations in the day prior to presentation.

Subsequent laboratory testing revealed a urine drug screen positive for tetrahydrocannabinol, but not benzodiazepines. Electrocardiogram demonstrated sinus tachycardia without ischemic changes. During further emergency department evaluation, the patient became increasingly agitated with worsening auditory, visual, and tactile hallucinations. He ultimately required sedation and intubation due to ongoing agitation and was admitted to the medical ICU for further management.

Following ICU admission, he remained intubated on a propofol infusion. Intravenous phenobarbital was utilized for neuroprotection in the setting of suspected severe benzodiazepine withdrawal. After 24 hours, dexmedetomidine was initiated to allow for slow propofol weaning, and he was subsequently extubated. He was transitioned to the Clinical Institute Withdrawal Assessment (CIWA) protocol with lorazepam for monitoring and treatment of additional withdrawal symptoms.

The patient was subsequently transferred to a general medical floor for further management. He reported ongoing auditory and visual hallucinations thought to be consistent with delirium in the setting of benzodiazepine withdrawal, which were managed with as-needed quetiapine. Psychiatry and social work consultations were obtained and recommended connection with resources for substance use assessment and treatment. A formal chemical dependency assessment was scheduled shortly after discharge from the hospital.

Additional psychiatry follow-up was also arranged with an integrated behavioral health provider in the primary care setting. During this assessment, further questioning confirmed the patient’s history of social anxiety with use of benzodiazepines and cannabis to self-manage anxiety symptoms. Pharmacologic treatment was initiated with buspirone to address anxiety, and outpatient psychotherapy was recommended as well. To date, the patient has not required re-hospitalization for substance use or psychiatric concerns.

Conclusion & Discussion: The first aim of this poster is to equip addiction medicine providers with knowledge about the evolving clinical effects of designer benzodiazepines. Similar to their licensed counterparts, designer benzodiazepine use may result in anxiolysis, amnesia, and sedation. As such, use of these compounds has been reported to address symptoms related to anxiety or sleep (1,2). This pattern was exemplified in this case with the patient subsequently reporting significant anxiety symptoms during a psychiatric evaluation.

Second, clinical professionals may benefit from a review of the current approaches to testing for designer benzodiazepine use. Contemporary immunoassays are thought to generally cross-react with many designer benzodiazepines; however, challenges exist when drug metabolites are not identified by these tests (3).

Finally, it is relevant to review current legal trends related to designer benzodiazepines. Bromazolam was involved in over 2,900 law enforcement seizures in 2023, which represents a marked increase from prior years (4). The United States Drug Enforcement Administration has also temporarily scheduled five designer benzodiazepines under schedule I of the Controlled Substances Act (5). In summary, the implications of designer benzodiazepine use can be profound, and this class of substances represents an emerging area of concern for addiction medicine professionals.

References: 1) Wilde M, Auwärter V, Moosmann B. New psychoactive substances - designer benzodiazepines. WIREs Forensic Science. 2021 Mar 28;3(6). doi: 10.1002/wfs2.1416.

2) Greenblatt HK, Greenblatt DJ. Designer Benzodiazepines: A Review of Published Data and Public Health Significance. Clin Pharmacol Drug Dev. 2019 Apr;8(3):266-269. doi: 10.1002/cpdd.667. Epub 2019 Feb 7. PMID: 30730611.

3) Marin M, Van Wijk X. The Evolution of Designer Benzodiazepines. Association for Diagnostics & Laboratory Medicine [Internet]. 2019 Nov. https://www.myadlm.org/cln/articles/2019/november/the-evolution-of-designer-benzodiazepines.

4) Ehlers PF, Deitche A, Wise LM, Patrick SL, Holloway-Beth A, Ellison R, Trecki J, Gerona R, Wahl MS. Notes from the Field: Seizures, Hyperthermia, and Myocardial Injury in Three Young Adults Who Consumed Bromazolam Disguised as Alprazolam - Chicago, Illinois, February 2023. MMWR Morb Mortal Wkly Rep. 2024 Jan 5;72(5253):1392-1393. doi: 10.15585/mmwr.mm725253a5. PMID: 38175814.

5) United States Drug Enforcement Administration. Five Synthetic Benzodiazepine Drugs Deemed Imminent Hazard to Public Safety. DEA Diversion Control Division [Internet]. 2023 Sep. https://www.dea.gov/stories/2023/2023-09/2023-09-25/five-synthetic-benzodiazepine-drugs-deemed-imminent-hazard-public.