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Tnp3.8
Tianeptine Research
Mostly mechanism / observationalLimited safety
6 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Tianeptine studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality meta-analyses and randomised trials published 2002–2018.
Based on 6 studies · 1 meta-analysis · 2 RCTs
Confidence
Moderate
By outcome
Safety profile
Mostly mechanism / observational6 studies
Antidepressant effect
Mostly mechanism / observational4 studies
Anxiety & anxious depression
Too few graded studies1 study
Glutamatergic plasticity & stress remodelling
Too few graded studies1 study
Older research base
Newest study from 2018 · Latest meta-analysis: 2002
200220102018
1Meta-Analysis2002
None of the assessed parameters (MADRS total score and responder rate) revealed any significant difference between the two treatment groups ... tianeptine is at least as effective as SSRI, with a trend for a better acceptability profile in the treatment of depressed patients.
Kasper S, Olié JP. · European Psychiatry (2002)
Meta-analysis of five randomized controlled trials (1,348 patients: 667 tianeptine, 681 SSRI) comparing short-term antidepressant efficacy of tianeptine versus fluoxetine, paroxetine and sertraline
No significant difference between tianeptine and SSRIs on MADRS total score or responder rate — tianeptine at least as effective as SSRIs
A trend favoured tianeptine on the CGI therapeutic-index item (better acceptability), supporting comparable efficacy with possibly better tolerability at the therapeutic dose
Tianeptine appears to be as effective and as safe as paroxetine for the ambulatory treatment of major depression.
Waintraub L, Septien L, Azoulay P. · CNS Drugs (2002)
3-month randomized, double-blind trial in 277 outpatients with major depression: tianeptine 12.5 mg three times daily versus paroxetine 20 mg/day across 82 French centres
Both groups showed significant improvement in depression scores with no meaningful difference between treatments
Tianeptine was as effective and as safe as paroxetine for ambulatory major depression at the therapeutic dose
Both drugs were effective and well tolerated in the treatment of major depression, with 75% of tianeptine-treated and 67% of fluoxetine-treated patients meeting responder criteria.
Novotny V, Faltus F. · Human Psychopharmacology (2002)
6-week randomized, double-blind multicentre trial in 178 patients with major depression: tianeptine 37.5 mg/day versus fluoxetine 20 mg/day
Comparable responder rates (75% tianeptine vs 67% fluoxetine) with good tolerability for both
Reinforces the meta-analysis with an independent head-to-head RCT showing tianeptine matches an SSRI at the therapeutic dose
Tianeptine is an efficacious mu-opioid receptor (MOR) agonist ... activation of MOR (or dual activation of MOR and DOR) could be the initial molecular event responsible for triggering many of the known acute and chronic effects of this agent, including its antidepressant and anxiolytic actions.
Gassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D. · Translational Psychiatry (2014)
Radioligand-binding and cell-based functional assays establishing tianeptine as a full mu-opioid receptor (MOR) agonist (Ki ~383 nM; EC50 ~194 nM for G-protein activation) and a lower-potency delta-opioid agonist, inactive at the kappa receptor
Identifies mu-opioid agonism as the likely molecular trigger for tianeptine's antidepressant and anxiolytic effects
Mechanistic basis for BOTH its therapeutic action AND its abuse/dependence/withdrawal liability — the single most important pharmacology finding for harm reduction
Tianeptine exposure calls, including those for intentional abuse or misuse, increased across the United States during 2014-2017, suggesting a possible emerging public health risk ... a substantial number of tianeptine exposure calls also reported clinical effects of withdrawal.
El Zahran T, Schier J, Glidden E, Kieszak S, Law R, Bottei E, Aaron C, King A, Chang A. · MMWR. Morbidity and Mortality Weekly Report (2018)
National Poison Data System surveillance of all US tianeptine exposure calls, 2000-2017 — a population-level signal of misuse and harm
Exposures rose sharply over 2014-2017, mostly in adults aged 21-40, with neurologic, cardiovascular and gastrointestinal effects, some mimicking opioid toxicity; a substantial number reported withdrawal
Common coexposures were phenibut, ethanol, benzodiazepines and opioids — the dangerous-combination signal
Tianeptine is a drug with potential for abuse and addiction ... caution is advised when prescribing tianeptine to patients with a history of substance abuse, with close monitoring during treatment.
Springer J, Cubała WJ. · Journal of Psychoactive Drugs (2018)
Structured review of 18 published case reports of tianeptine abuse and dependence in psychiatric patients
Documents a clear pattern of abuse and addiction with dose escalation to many times the therapeutic dose and opioid-like withdrawal, concentrated in patients with prior substance-use disorder
Concludes tianeptine has genuine abuse/addiction potential and warrants caution and monitoring when prescribed