Management of xylazine toxicity, overdose, dependence, and withdrawal: A systematic review

Xylazine, an alpha-2-adrenergic agonist, has been increasingly implicated in substance use and overdose crises. However, little is known about its effects on humans. With the growing public health crisis surrounding xylazine, it has become important to recognize and promptly manage symptoms of xylazine toxicity, withdrawal, and overdose. We conducted a systematic review to consolidate the existing literature on the topics, aiming to identify gaps and propose evidence-based actions for managing patients.

Published literature from 1957 to 2024 was searched to identify studies focusing on the management of xylazine intoxication, withdrawal, overdose, and dependence in humans. PRISMA guidelines and JBI critical appraisal tools were used to ensure the methodological quality of the included studies and reduce bias in study selection. Thirty-four studies were included in this review.

Xylazine misuse was common among men aged 19-45 years and was more likely to be used with other substances than alone. The doses ranged from 40 to 4300 mg, with no established toxic dosing. Supportive care included treatment with naloxone, alpha-2 agonists, and GABAergic medications. There is no antidote or evidence-based treatment recommendations.

This systematic review consolidated the outcomes and proposed guidelines from xylazine management trials. It can serve as a reference for providers to promptly manage xylazine toxicity, withdrawal, and overdose symptoms to improve patient outcomes.

Although there is currently no standardized treatment or antidote, this review will aid ongoing research to address these gaps in xylazine management.