Pharmaceutical

Tianeptine

7-[(3-Chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide

Evidence TierAWADA NOT PROHIBITED

tuneTypical Dose

37.5

watchEffect Window

Acute mood lift within 1 hour. 2-4 weeks for neuroplastic antidepressant effects.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Tianeptine is an atypical antidepressant with mu-opioid receptor activity and effects on glutamatergic stress pathways. It is used for depression and anxiety in some countries, with notable misuse risk.

Clinical trials support efficacy for depression and anxiety, with favorable effects on some cognitive symptoms and lower sexual side effect rates than certain antidepressants. Some studies suggest improved stress resilience and somatic symptoms. Minority evidence explores IBS-related and pain outcomes. Misuse and dependence risk are significant, constraining net benefit and requiring careful clinical oversight where prescribed.

Atypical antidepressant acting via mu-opioid receptor agonism, glutamatergic modulation, and BDNF upregulation. Formerly misclassified as a selective serotonin reuptake enhancer.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Effective treatment for Major Depressive Disorder comparable to SSRIs with superior tolerability at clinical doses.

Secondary Outcomes

  • No sexual dysfunction or emotional blunting commonly associated with SSRIs.

Safety

Contraindications and Interactions

Contraindications

  • Opioid use disorder
  • Concurrent MAOIs
  • History of substance abuse

Side effects

  • Nausea
  • Constipation
  • Abdominal pain
  • Headache
  • Dizziness
  • Dry mouth
  • Insomnia

Interactions

  • MAOIs (absolute contraindication)
  • Opioids (additive)
  • CNS depressants
  • Kratom

Avoid if

  • History of substance abuse or addiction
  • Opioid use disorder

Evidence

Study-level References

tianeptine-SRC-001Meta-analysis of RCTs
Sourceopen_in_new

Kasper S, Olié JP. "A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression." Eur Psychiatry. 2002.

Population: Adults with Major Depressive Disorder

Key findings: Tianeptine 37.5 mg/day is as effective as SSRIs (fluoxetine, paroxetine, sertraline) in treating MDD and demonstrates a better safety/tolerability profile, particularly regarding gastrointestinal and sexual side effects.

Paper content

Tianeptine 37.5 mg/day is as effective as SSRIs (fluoxetine, paroxetine, sertraline) in treating MDD and demonstrates a better safety/tolerability profile, particularly regarding gastrointestinal and sexual side effects.

tianeptine-SRC-002Systematic review and exploratory analysis.
Sourceopen_in_new

Parnia S, Jain L, Ali M, Sarfraz Z, Nasir MJ, Shah D, Fnu A, Atiq N, Shaikh PR, Ahmed R, Hower M, Karlapati S, Moazzam MT, Bazin B, Ahmed S. Gas station heroin- tianeptine and its impact: a systematic review and exploratory analysis. BMC Public Health. 2025;25:3591. doi:10.1186/s12889-025-24666-0. PMID:41136982.

Population: Individuals with tianeptine exposure or misuse reported in published literature.

Dose protocol: Systematic review of 25 studies on tianeptine misuse

Key findings: Habitual misuse in 57.69% of cases, overdoses in 34.62%, withdrawal in 42.31%. North America represented 76.92% of cases. Naloxone effective in 17.31% of treated overdose cases.

Notes: Reinforces the opioid-like abuse liability and public health impact of unregulated tianeptine access.

Paper content

This systematic review synthesized 25 studies on tianeptine misuse patterns. North America accounted for 76.92% of cases, with predominantly male users (55.77%) using oral routes (71.15%). Habitual misuse occurred in 57.69% of cases, overdoses in 34.62% (frequently involving alcohol or benzodiazepines), and withdrawal symptoms in 42.31%. Naloxone was effective in 17.31% of treated cases, confirming the opioid-receptor-mediated mechanism of toxicity. Buprenorphine and supportive care were used for withdrawal management. The review reinforces concerns about tianeptine's opioid-like abuse liability and the public health impact of unregulated access, particularly in the United States where it is sold as a supplement or nootropic.

tianeptine-SRC-003Retrospective database analysis.
Sourceopen_in_new

Quadir M, Rine NI, Badeti J, Hays HL, Michaels NL, Yang J, Smith GA. Tianeptine Exposures Reported to United States Poison Centers, 2015-2023. J Med Toxicol. 2025;21(1):30-41. doi:10.1007/s13181-024-01053-6. PMID:39724478.

Population: Individuals with tianeptine exposure reported to US poison centers from 2015 to 2023.

Dose protocol: Retrospective analysis of 892 US poison center tianeptine exposures (2015 to 2023)

Key findings: 1,400% increase in exposures over the study period. 40.1% hospitalization rate. Alabama scheduling led to 74.6% decline in that state's exposures.

Notes: Provides strong epidemiological evidence for regulatory intervention efficacy.

Paper content

This analysis of 892 single-substance tianeptine exposures reported to US poison centers between 2015 and 2023 documented a 1,400% increase over the study period. Most cases resulted in moderate (51.5%) or major (12.0%) effects, with 40.1% requiring hospitalization. Abuse accounted for 40.1% of exposures and was associated with worse outcomes. Withdrawal symptoms were reported in 22.5% of cases. Older adults (50+) experienced greater severity. Southern US states had the highest exposure rates. Alabama's 2021 scheduling of tianeptine as a controlled substance led to a 74.6% decline in that state's exposures, providing evidence that regulatory action can reduce harm. The data strongly support the need for broader regulation of tianeptine in the United States.

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