Bromazolam Sold as Alprazolam: Seizures, Fever and Heart Injury in Three Young Adults

Bromazolam is expected to act like other benzodiazepines — mainly as a sedative, going by animal studies — and nothing had linked it to fever, heart injury or seizures. Then three young adults near Chicago took pills they believed were alprazolam. The pills were bromazolam, and all three developed seizures and heart injury, two of them with fever: a picture CDC's report calls unexpected for a benzodiazepine overdose.

What bromazolam is

• A "designer" triazolobenzodiazepine, first synthesized in 1976 and never approved for therapeutic use.
• First detected in Sweden in 2016. Since then it has turned up more and more often, both alongside fentanyl in toxicology tests and in counterfeit benzodiazepine pills — misrepresented as a benzodiazepine approved by the Food and Drug Administration.
• U.S. law enforcement seizures involving it rose from no more than three a year in 2016–2018 to 2,142 in 2022 and 2,913 in 2023 (with 2023 data still being reported).
• In Illinois, deaths involving bromazolam rose from 10 in 2021 to 51 in 2022.
• It is mostly found with fentanyl or other opioids — in 88%–100% of tested samples — but it can be life-threatening even without other drugs.

Three patients

On February 1, 2023, in a southern suburb of Chicago, three previously healthy young adults — two men aged 25 (patients A and B) and a woman aged 20 (patient C) — swallowed pressed tablets they believed were alprazolam. Alprazolam is prescribed for anxiety and panic disorders, and misused recreationally for the disinhibition and euphoria it causes. About 8 hours later, patient A's mother found all three unresponsive.

Emergency medical services gave naloxone, with no response. All three arrived at emergency departments unresponsive (A and B at one, C at another), were intubated, and had myocardial injury shown by raised troponin. Their urine tested positive for benzodiazepines. None received flumazenil, a benzodiazepine overdose antidote that can itself bring on benzodiazepine withdrawal and cause seizures or fast abnormal heart rhythms. All went to intensive care, and the Illinois Poison Center helped with their evaluation and treatment.

Testing by the Drug Enforcement Administration's Toxicology Testing Program (DEA TOX) confirmed bromazolam in all three, and no fentanyl or any other opioid.

Why the picture is puzzling

The report offers three possible explanations for these severe effects:

1. brain injury from lack of oxygen during the long period the patients were unresponsive;
2. effects of bromazolam itself, in overdose or withdrawal, that had not been described before;
3. another intoxicant that the laboratory method (liquid chromatography–mass spectrometry) did not detect.

For comparison, since 2021, 114 cases analyzed through DEA TOX have tested positive for bromazolam, with a mean blood level of 44.8 ng/mL. It has also been found in drivers arrested for driving under the influence, where it produced a largely sedative picture.

What the report asks of clinicians

• Know it is out there, in mixed-drug overdoses and among patients with substance use disorders who report using benzodiazepines.
• Use it in treatment. Knowing the drug helps with prognosis — two of the three patients recovered to near independence — and may point to the need for aggressive seizure control.
• Consider bromazolam when a patient needs treatment for seizures, myocardial injury or hyperthermia after illicit drug use, and when a sedated patient does not respond adequately to naloxone.
• Call the poison center for guidance, and involve public health officials, since these cases were more severe than a routine benzodiazepine overdose.
• Arrange testing through a send-out reference laboratory — such as NMS Labs, Quest Diagnostics or DEA TOX — since it is not routinely available in hospital labs.

Sources

Based on "Notes from the Field: Seizures, Hyperthermia, and Myocardial Injury in Three Young Adults Who Consumed Bromazolam Disguised as Alprazolam — Chicago, Illinois, February 2023," by Paul F. Ehlers and colleagues (Toxikon Consortium, Illinois Poison Center, Illinois Department of Public Health, Cook County Department of Public Health, University of California San Francisco, Drug Enforcement Administration), Morbidity and Mortality Weekly Report (MMWR), from the Centers for Disease Control and Prevention; a work of the United States government in the public domain. Figures on law enforcement drug seizures come from the National Forensic Laboratory Information System (queried December 14, 2023) and death figures from Illinois vital records.