Case Presentation: A 39-year-old male with a history of benzodiazepine (BZD) use disorder, anxiety, and post-traumatic stress disorder presented to our academic medical center after a seizure in the setting of a self-directed bromazolam taper. He was prescribed BZDs 15 years ago for anxiety and insomnia, but he began to self-medicate with illicitly purchased bromazolam when his clinician was no longer willing to prescribe. To reduce his escalating use, he started a 10% weekly taper two months ago. He was taking 24 mg daily when his taper began and 14 mg daily by the time of admission. He traveled without the bromazolam and had a seizure 48 hours after his last dose, which led to admission to the intensive care unit. Toxicology and Addiction Medicine were consulted. He was started on the Minnesota Detoxification Scale (MINDS) protocol with symptom-triggered phenobarbital dosing. Despite receiving 15mg/kg phenobarbital (1,350mg), he experienced another seizure. He completed a maximum phenobarbital load of 30mg/kg (2,700mg), but continued to experience withdrawal symptoms. He was started on scheduled BZDs on hospital day 4, which eventually controlled his remaining withdrawal symptoms. Significant coordination with community clinicians was required to ensure a continued outpatient BZD taper would be possible. He was discharged on diazepam 20 mg twice daily with a plan for a slow taper outpatient by an addiction medicine clinician in his community.
Discussion: Bromazolam is a designer BZD a term that refers to illicit BZD derivatives that are not approved for use in the United States and is increasingly encountered as a psychoactive adulterant of other illicit drugs. It is similar in structure and potency to alprazolam but is not detected by standard toxicology screens. There is limited data on its pharmacokinetics and management of its withdrawal. BZDs enhance GABA activity at GABA-A receptors. Thus, endogenous GABA must be present for BZDs to be effective. Chronic BZD use causes downregulation of endogenous GABA, and heavy use may lead to withdrawal that is refractory to typical BZD administration. Prescribed BZDs are tapered over months to years due to the significant time it takes for endogenous GABA and GABA-A receptors to reestablish homeostasis. Determining an equivalent BZD dose is challenging with illicit products, so clinicians should titrate to the minimum dose that controls withdrawal and taper from there. This approach is often not possible for patients using illicit BZDs because most outpatient prescribers do not feel safe providing an outpatient taper, despite that approach being recommended by clinical practice guidelines. Withdrawal in the setting of illicit use can usually be managed using an inpatient phenobarbital taper that occurs over 3-5 days. This is possible because phenobarbital directly activates GABA-A receptors, without relying on endogenous GABA, decreases glutamate activity and has a very long half-life.
Conclusions: Our case highlights the emerging clinical challenges in managing withdrawal from potent designer BZDs like bromazolam. Despite 30 mg/kg of phenobarbital, our patient experienced persistent withdrawal symptoms and required an additional BZD taper. The need for an ongoing BZD taper impacted our ability to discharge the patient and required significant coordination with community substance use clinicians. Our case contributes to the growing literature describing potential treatment approaches and underscores the challenges hospitals may face with rising designer BZD use.