Characteristics of Medetomidine Withdrawal Among People With Concurrent Fentanyl Use

The potent α2-adrenergic agonist medetomidine has emerged as an adulterant in the unregulated US fentanyl supply in several communities. In some instances, people with non-medical fentanyl use have presented to the hospital with withdrawal symptoms that do not respond to opioid therapy and include severe autonomic hyperactivity (i.e., hypertension, tachycardia, vomiting, refractory delirium), suspected to be due to concurrent medetomidine withdrawal. This retrospective case series sought to characterize medetomidine withdrawal syndrome across three hospital systems in Philadelphia, PA, 2024–2025.

• Among 209 hospitalized patients who presented with fentanyl withdrawal and atypical autonomic instability, the median age was 38 years; 29 percent were female, and 64 percent identified as White.
• 162 patients (78 percent) required intensive care unit (ICU) admission, with 42 patients (20 percent) needing intubation. Tachycardia and hypertension were common, and most patients (74 percent) required dexmedetomidine infusions for autonomic hyperactivity.
• Common complications included encephalopathy (35 percent) and myocardial injury (29 percent). Seizure was uncommon (5 percent), and primarily affected patients with concurrent benzodiazepine use. Thirty-three percent of patients had a patient-directed discharge.
• Among a subset of 43 patients, urine toxicology with liquid chromatography–mass spectrometry confirmed 100 percent positivity for fentanyl and medetomidine metabolites.

Comments: This cohort of patients with medetomidine-adulterated fentanyl withdrawal experienced severe sympathetic hyperactivity, resulting in high rates of ICU admission, intubation, and patient-directed discharge. Clinicians should recognize this withdrawal syndrome and treat autonomic hyperactivity with early administration of α2-agonist therapy.

Delia Motavalli, MD* & Alexander Y. Walley, MD

* Contributing Editorial Intern and Addiction Medicine Fellow, Boston Medical Center

Reference: London KS, Huo S, Murphy L, et al. Severe fentanyl withdrawal associated with medetomidine adulteration: a multicenter study from Philadelphia, PA. J Addict Med. 2025 [Epub ahead of print]. doi: 10.1097/ADM.0000000000001560.