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2023 Tox Trends: Tianeptine and Xylazine

Andy Little, DO and Jess Rivera Pescatore, PharmD

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The summary below is from an episode of ERcast: Clinical Perspectives

Tianeptine and xylazine are emerging drugs of abuse that can look like opioid toxicity but behave differently at the bedside. Tianeptine is a mu-opioid receptor agonist sold in the US as an unregulated supplement, while xylazine is a veterinary alpha-2 agonist that often adulterates fentanyl and can cause prolonged CNS depression.

Tianeptine toxicity and withdrawal

  • Gas station opioid mimic: Tianeptine was developed as an antidepressant but in the US is sold as a supplement with strong mu-opioid receptor activity, making overdose and dependence easy to miss.
  • Mixed overdose phenotype: Acute intoxication often resembles opioid overdose yet can include marked agitation alongside CNS depression, a combination that should prompt a broader tox screen.
  • Naloxone responsive toxicity: Naloxone is a reasonable first-line antidote for tianeptine intoxication, but airway monitoring matters because reversal can be incomplete or precipitate abrupt withdrawal.
  • Severe withdrawal syndrome: Tianeptine withdrawal can be dramatic enough to require chemical sedation, with benzodiazepines and other ICU-level adjuncts often entering the conversation. We get into the practical sedation approach in the episode.
  • Patient education opportunity: Some patients take tianeptine for mood, weight loss, or self-detox and may not realize it is non-FDA-approved, so bedside counseling is part of harm reduction.

Xylazine intoxication and complications

  • Veterinary sedative adulterant: Xylazine is an FDA-approved veterinary sedative and a potent alpha-2 agonist that increasingly appears alone or mixed with fentanyl to prolong effect.
  • Naloxone-resistant sedation: Profound CNS depression, lethargy, and miosis are typical, but unlike pure opioid overdose the clinical response to naloxone may be limited or absent.
  • Airway over antidote: Supportive care is the priority because symptoms can persist up to 12 hours, and many patients need oxygen, ventilation support, or admission for observation.
  • Hemodynamic red flags: Bradycardia and hypotension are less common than sedation but are important clues when the toxidrome does not fit routine fentanyl exposure. We cover the bedside recognition nuances in the chapter.
  • Necrotic skin ulcers: Chronic xylazine exposure is linked to necrotic ulcerations, especially on the hands and feet, a finding that can point to the diagnosis when ED testing is unavailable.

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References:

  1. Rushton W, et al. Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health. Clin Toxicol (Phila). 2021;59(2):152-157. Epub 2020 Jun 18. PMID: 32552075.
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  8. Reed MK, et al. Perspectives of people in Philadelphia who use fentanyl/heroin adulterated with the animal tranquilizer xylazine; Making a case for xylazine test strips. Drug Alcohol Depend Rep. 2022;4:100074. PMID: 36846574.
  9. Malayala SV, et al. Xylazine-Induced Skin Ulcers in a Person Who Injects Drugs in Philadelphia, Pennsylvania, USA. Cureus. 2022;14(8):e28160. PMID: 36148197.

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