Tianeptine toxicity

Background

• Tianeptine is an atypical antidepressant that has different effects on multiple neurochemicals and receptors including serotonin, glutamate, NMDA, and opioid
• Full μ-opioid receptor agonism can lead to effects similar to opioid toxicity and overdose
• From 2014-2017 the USA saw a large increase in reported cases of tianeptine toxicity thought to be due to the discovery of its opioid effects and its ability to induce euophoria; it can be purchased online as a dietary supplement or research chemical
• Not FDA approved in the USA, still used in other countries as a treatment for depression

Clinical Features

• May share features of different toxicologic syndromes due to multiple receptors/neurotransmitters affected including opioid overdose and serotonin syndrome
• AMS
• Agitation
• Coma
• Respiratory depression
• Diaphoresis
• Nausea
• Vomiting
• Diarrhea
• Tachycardia
• Hypertension
• Mydriasis or miosis

Differential Diagnosis

Sedative/hypnotic toxicity

• Absinthe
• Barbiturates
• Benzodiazepines
  • Flunitrazepam (Rohypnol)
• Chloral hydrate
• Gamma hydroxybutyrate (GHB)
• Baclofen toxicity
• Opioids
  • Lomotil toxicity
  • Loperamide toxicity
• Toxic alcohols
  • Ethanol
  • Ethylene glycol
  • Isopropyl alcohol
  • Methanol
• Xylazine toxicity

Toxidrome Chart

Finding	Cholinergic	Anticholinergic	Sympathomimetic	Sympatholytic^	Sedative/Hypnotic
Example	Organophosphates	TCAs	Cocaine	Clonidine	ETOH
Temp	Nl	Nl / ↑	Nl / ↑	Nl / ↓	Nl / ↓
RR	Variable	Nl / ↓	Variable	Nl / ↓	Nl / ↓
HR	Variable	↑	↑ (sig)	Nl / ↓	Nl / ↓
BP	↑	↑	↑	Nl / ↓	Nl / ↓
LOC	Nl / Lethargic	Nl, agitated, psychotic, comatose	Nl, agitated, psychotic	Nl, Lethargic, or Comatose	Nl, Lethargic, or Comatose
Pupils	Variable	Mydriatic	Mydriatic	Nl / Miotic
Motor	Fasciculations, Flacid Paralysis	Nl	Nl / Agitated	Nl
Skin	Sweating (sig)	Hot, dry	Sweating	Dry
Lungs	Bronchospasm / rhinorrhea	Nl	Nl	Nl
Bowel Sounds	Hyperactive (SLUDGE)	↓ / Absent	Nl / ↓	Nl / ↓

^Consider Sympatholytic when looking at Sedative OD or someone who doesn't respond to Narcan

Withdrawal from substances have the opposite effect

Evaluation

• Mainly a clinical diagnosis
• Assess airway first to determine need for intubation
• POC glucose
• EKG - look for widened QRS, prolonged QTc
• Basic labs
• Urine tox screen

Management

• Airway management
  • Intubation if necessary
• Oxygen for hypoxia
• Naloxone has been successfully used to treat at least one case in the literature but data is limited
• Benzodiazepines for agitation

Disposition

• Depends on severity of toxicity
  • Admit to floor vs ICU