Mechanism • MOR
#
Landmark: tianeptine is a μ-opioid receptor agonist
Bench pharmacology establishing MOR agonism—key to understanding euphoria, dependence, and naloxone responsiveness.
Summary
Gassaway et al. demonstrate MOR agonism with functional assays, reframing tianeptine’s risk profile beyond “atypical antidepressant.”
Gassaway MM, Rives M-L, Kruegel AC, Javitch JA, Sames D. The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. ACS Chem Neurosci. 2014;5(6):476-484. PMC
Mechanism • Glutamate
#
Neurobiology review: glutamate & stress-circuit modulation
Authoritative review linking glutamatergic modulation/neuroplasticity to clinical effects—distinct from SSRIs.
Summary
McEwen et al. synthesize hippocampal AMPA/NMDA signaling, synaptic plasticity, and stress-axis effects relevant to mood and resilience.
McEwen BS, Chattarji S, Diamond DM, et al. The neurobiological properties of tianeptine (Stablon). Eur Psychiatry. 2010;25(5):244-249. PMC
Mechanism • MOR dependence (animal)
#
Rapid antidepressant-like effects require MORs (mouse)
In vivo work indicates MOR requirement for behavioral effects—supports opioid-like liability.
Summary
Hippocampal circuitry and GABAergic targets implicated; clarifies why withdrawal resembles other opioids.
Han J, et al. Mu opioid receptors on hippocampal GABAergic neurons mediate tianeptine’s rapid antidepressant-like effects. Biol Psychiatry. 2022. PMID: 34593976. PubMed
Mechanism • AMPA/NMDA
#
AMPA/NMDA signaling modulation in hippocampus
Shows persistent modulation of glutamatergic transmission—mechanistic basis for neuroplastic effects.
Summary
Demonstrates receptor-level effects that align with clinical observations of mood stabilization and resilience.
Kole MHP, et al. The antidepressant tianeptine persistently modulates AMPA receptor-mediated synaptic transmission. PNAS. 2002;99(10):6394-6399. PMID: 12372016. PubMed
Clinical Review
#
Narrative clinical review: opioid-like risks & management
Summarizes misuse, dependence, withdrawal, naloxone responsiveness, and treatment considerations.
Summary
Practical counseling primer for ED, addiction, and primary care; outlines regulatory landscape and product concerns.
Edinoff AN, et al. Tianeptine, an Antidepressant with Opioid Agonist Effects. Psychopharmacol Bull. 2023;53(3):68-88. PMC
Epidemiology • NPDS (MMWR)
#
National poison-center signal: U.S. exposures (2000–2017)
Escalating calls with opioid-like toxidrome; naloxone often helpful—early national alert for clinicians and public health.
Summary
Describes demographics, common effects (respiratory depression, agitation, seizures), routes (oral most common), and co-exposures; provides surveillance baseline for later outbreaks.
El-Zahran T, Wolkin A, Yin S, et al. Characteristics of Tianeptine Exposures Reported to the National Poison Data System — United States, 2000–2017. MMWR Morb Mortal Wkly Rep. 2018;67(30):815–818. PubMed • CDC
Epidemiology • Regional Poison Center
#
Poison-center cohort: intoxication vs. withdrawal
About two-thirds of calls were withdrawal; intoxication cases frequently naloxone-responsive—actionable ED guidance.
Summary
Outlines symptom patterns, treatment responses, and disposition; highlights “gas-station” product sources and recurrent use leading to dependence.
Rushton WF, Hall MK, Martin S, et al. Characteristics of tianeptine effects reported to a poison control system. Clin Toxicol (Phila). 2021;59(8):665–671. PubMed
Epidemiology • NPDS (Update)
#
Updated NPDS analysis: rapid rise in U.S. exposures
Shows sharp recent growth in tianeptine calls; supports consistent state-level regulation to reduce harm.
Summary
Breaks down age groups, clinical effects, co-ingestants, and medical outcomes; contextualizes policy responses and retail access.
Quadir M, Islam N, Kumar A, et al. Tianeptine Exposures Reported to United States Poison Centers. Clin Toxicol (Phila). 2025;XX(X):XX–XX. PMID: 39724478. PubMed
Surveillance • ED & Fatalities
#
ED visits, fatal poisonings, and product sales
Documents ED presentations (seizure, respiratory depression, LOC) and fatal cases; integrates sales surveillance for context.
Summary
Multi-source public-health analysis linking clinical outcomes to availability; includes naloxone responses and co-exposure patterns.
Hershey HL, Proudfoot J, Roberts H, et al. Tianeptine-involved emergency department visits, fatal poisonings, and sales. J Emerg Med. 2024;66(5):e153–e163. PMC
Outbreak • Neptune’s Fix
#
State outbreak tied to branded tianeptine product
Cluster (≈34 cases) with severe toxicity after a popular gas-station brand; shows investigation & response steps.
Summary
Describes case definitions, lab confirmation, syndromic surveillance triggers, and coordinated actions across health departments and law enforcement.
Counts CJ, Balasubramanian G, Chui K, et al. An Outbreak of Synthetic Cannabinoid-Adulterated Tianeptine Leading to Severe Toxicity — New Jersey, 2023–2024. Clin Toxicol (Phila). 2025;XX(X):XX–XX. PMID: 40102319. PMC (author version)
Forensic • Fatalities
#
Fatalities involving tianeptine (U.S. case reports)
Two confirmed tianeptine-only deaths; establishes intrinsic lethality at high doses.
Summary
Autopsy and toxicology results demonstrate respiratory failure and high serum levels without co-intoxicants; emphasizes need for postmortem testing.
Bakota E, et al. Case Reports of Fatalities Involving Tianeptine in the United States. J Anal Toxicol. 2018;42(7):e41-e45. PMID: 29566235. PubMed
Toxicology • IV use
#
Acute toxicity from intravenous tianeptine
First report of IV use causing severe toxicity—recognition crucial for ED teams.
Summary
Patients injected dissolved tablets; developed acidosis, rhabdomyolysis, renal failure; survived with supportive care.
Dempsey SK, et al. Acute Toxicity From Intravenous Use of the Tricyclic Antidepressant Tianeptine. J Med Toxicol. 2017;13(3):306-309. PMC
Dependence • U.S. Case
#
Early U.S. case of dependence and withdrawal
Online-purchased tianeptine produced dose escalation and opioid-like withdrawal syndrome.
Summary
Demonstrates availability via internet suppliers and classic withdrawal: anxiety, tremor, myalgia, insomnia; highlights regulatory gap.
Gupta S, et al. A Case Report of Tianeptine Use in the United States. Am J Addict. 2017;26(7):815-818. PMID: 28742625. PubMed
Treatment • Buprenorphine/Naloxone
#
Buprenorphine-naloxone for tianeptine use disorder
Demonstrates effective stabilization and maintenance using B/N therapy.
Summary
Patient transitioned successfully with resolution of cravings and withdrawal; parallels opioid-use-disorder treatment protocols.
Trowbridge P, et al. Use of Buprenorphine-Naloxone in the Treatment of Tianeptine Use Disorder. J Addict Med. 2019;13(1):80-82. PMID: 30550394. PubMed
Treatment • Micro-Induction
#
Microdose induction (Bernese) with buprenorphine
Shows outpatient micro-induction feasible for heavy tianeptine users.
Summary
Case illustrates gradual B/N up-titration minimizing withdrawal; provides model for office-based treatment.
Szczesniak L, et al. Microdose Induction of Buprenorphine in a Patient Using Tianeptine. J Addict Med. 2022;16(6):e370-e372. PMID: 35709488. PubMed
Withdrawal • Inpatient Management
#
Medication-assisted inpatient management of severe withdrawal
Demonstrates structured inpatient protocol using buprenorphine, clonidine, and supportive therapy.
Rawal VY, et al. Inpatient Management of Severe Tianeptine Withdrawal Using Medication-Assisted Therapy. Subst Abuse Treat Prev Policy. 2025;XX(X):XX-XX. PubMed (preprint)
Withdrawal • Concurrent Substances
#
Concurrent tianeptine + etizolam withdrawal case
Highlights management complexity of multiple GABA-/opioid-acting supplements.
Markovic M, et al. Tianeptine and Etizolam Withdrawal Managed With Methadone and Diazepam. Clin Case Rep. 2023;11:e07654. PubMed
Overdose • Naloxone Responsive
#
Naloxone-responsive overdose with tianeptine
Confirms μ-opioid involvement—rapid reversal with naloxone in mixed antidepressant ingestion.
Ari M, et al. Naloxone-Responsive Coma After Combined Tianeptine and Amitriptyline Overdose. Clin Toxicol (Phila). 2010;48(5):472-475. PubMed
Informational only — not medical advice. Encourage disclosure of all “herbal” and imported supplement use.