II. Mechanism

  1. Antidepressant that increases brain uptake of Serotonin (5-HT) and increasing central Serotonin activity
    1. Unique to Tianeptine and in contrast with SSRIs that inhibit the synaptic reuptake of Serotonin
    2. Also modulates Glutamate
    3. Marketed legally in Europe, Asia and Latin America as an Antidepressant and Anxiolytic
      1. Not FDA approved or regulated in the U.S.
  2. Atypical and weak mu-Opioid receptor Agonist when used at high dose
    1. Available in the U.S. as a "dietary supplement", and often sold in gas station convenience stores
    2. Ilicit use for Opioid-like euphoria (typically at excessive doses that risk toxicity)
    3. Patients with addiction will use doses of 100 mg every 2 hours

III. Precautions

  1. NOT recommended for any use in the U.S.
  2. Risk of Drug Dependence as well as life threatening events (especially in Overdose)

IV. Pharmacokinetics

  1. Rapid oral absorption
  2. Half-Life: 2.5 hours

V. Dosing

  1. Depression dosing: 37.5 mg/day
  2. Illicit dosing as a Opioid-like agent reaches doses as high as 10,000 mg/day

VI. Adverse Effects: Toxic Doses

  1. General
    1. Diaphoresis
  2. Neurologic
    1. Agitation
    2. Lethargy
    3. Tremor
    4. Coma
  3. Respiratory
    1. Respiratory depression (deaths have occurred)
  4. Cardiovascular
    1. Tachycardia
    2. Hypertension
  5. Gastrointestinal
    1. Nausea or Vomiting
    2. Abdominal Pain

VII. Drug Interactions

  1. CNS Depressants (Benzodiazepines, Cannabinoids, Opioids)
    1. Potentiates effects of Tianeptine
  2. Monoamine Oxidase Inhibitors
    1. Cardiovascular collapse and Seizure risk (may be fatal)

VIII. Labs

IX. Management

  1. ABC Management
  2. Activated Charcoal
    1. Consider if presentation within 1 hour of ingestion
  3. Respiratory depression or apnea
    1. Consider Naloxone (may be ineffective)
  4. Agitation
    1. Benzodiazepines
  5. Withdrawal
    1. Consider Buprenorphine
  6. Disposition
    1. Consider observation for CNS depression

X. Complications

  1. Substance Abuse with dependence and withdrawal (similar to Opioid Toxicity and withdrawal)

XI. References

  1. (2025) Presc Lett 32(8): 48
  2. Tomaszewski (2024) Crit Dec Emerg Med 38(2): 34

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