Tianeptine Sodium was first discovered by French researcher Antoine Deslandes and Michael Spedding during the 1960’s, and subsequently patented by the French Society of Medical Research in 1971. Tianeptine is officially approved in some Asian, South American and European countries, under brand names such as Stablon, Coaxil and Tanitol.
Tianeptine is mainly prescribed to treat major depressive disorder, although recently, it’s been indicated for use with IBS and Asthma .
Tianeptine is a tricyclic antidepressant (TCA) and has a structure similar to other TCA’s such as amitriptyline and doxepin. However, Tianeptine’s mechanism of action is different to most common antidepressants and TCA’s in general.
Tianeptine’s lack of Approval
Although Tianeptine has been available in some countries for over 20 years, it’s still unapproved in many major western countries such as the USA, UK, Australia, Canada and New Zealand.
This is strange, especially considering the improved efficacy and safety profile Tianeptine holds over its competitors such as Prozac (Fluoxetine) and Celexa (Citalopram).
In short – there are many financial and political aspects regarding Tianeptine’s lack of approval in these countries. Frustratingly, although solid evidence proves Tianeptine’s rightful place among other common antidepressants; its approval has been vetoed due to many confounding variables based on money and politics, rather than scientific evidence, and patients best interest . Read more here.
Tianeptine Sodium: Approved & Unapproved Uses & Effects
Tianeptine has a plethora of approved medical uses. However, since Tianeptine lacks availability in many countries – Tianeptine is only sold for research purposes. This has led to a large amount of user submitted (anecdotal or “off-label”) uses.
Approved Medical Uses & Effects
Depression , Asthma, IBS, various anxiety disorders, alcohol withdrawal, anticonvulsant, analgesic (pain killing), depression-induced cognitive dysfunction , depression in Parkinsons disease , PTSD, erectile dysfunction, and ADHD. Neuroprotective , prevents hippocampal remodelling from stress .
Unapproved or Reported – “off-label” Uses & Effects
- Increased subjective motivation
- Anxiolitic (anti-anxiety)
- Euphoria 
- General Nootropic benefits 
- Improved Ability to Focus 
- Improved reaction time, learning and short-term memory retention .
Tianeptine’s Mechanism of action
Like many approved drugs, Tianeptine’s complete mechanism remains elusive to science, and only the best theories are put forward in the literature as best fit models.
Tianeptine is a tricyclic antidepressant (TCA). Usually, TCA’s act by increasing the cerebral levels of serotonin and norepinephrine, via an SNRI mechanism.
Initial studies found that Tianeptine helped alleviate depressive symptoms by decreasing extracellular level of serotonin, rather than increasing the release of serotonin, like other established antidepressants such as TCA’s and SSRI’s.
Therefore, Tianeptine was initially identified as one of the world’s first Selective Serotonin Re-uptake Enhancers (SRE or SSRE). However, upon further investigation, it was found that Tianeptine did not interact with the serotonin monoamine, nor did it alter extracellular levels of Serotonin in long-term studies.
To further Complicate the matter, Tianeptine (unlike most other SSRI’s) enhances the mesolimbic release of dopamine and potentiates various dopamine receptors. However, scientists have failed to understand this mechanism’s action with Tianeptine, due to the fact Tianeptine has no affinity for the dopamine transporter or receptors . So how does it work?
In July 2014, a team led by M M Gassaway at the University of Columbia, USA – identified Tianeptine as the world first ever selective full agonist at the μ-opioid and δ-opioid receptors without affecting κ-opioid receptors . Read more here.
Recent research has indicated a mechanism, which (so far) is the most widely accepted.
Tianeptine produces its antidepressants effects through an indirect pathway which alters glutamate receptor activity via the NMDA and AMPA receptors.
Furthermore, research indicates that Tianeptine’s glutamate action coupled with it stimulating the release of BDNF, allows for a change in neural plasticity.
Tianeptine: A Truly Unique Compound
Tianeptine is, undoubtedly, very unique. Since it’s discovery, many different mechanisms have been postulated, with no solid conclusion as to why Tianeptine is so effective against depression.
Tianeptine remains popular because it works. Millions of people worldwide suffer from symptoms that cannot be treated with the regularly approved medicines. Tianeptine’s efficacy has been affirmed, not only when other medications fail, but when it’s safety profile is compared to similar drugs – it’s clearly a better and safer treatment.
Based on the available literature, here is a list of the key properties which put Tianeptine in a completely different class to its rivals.
- Less toxicity than other medicines prescribed for the same indication.
- Less severe side effects when compared with other TCA’s, with a lower frequency. Such as significantly less sedation, cardiovascular (dry mouth or constipation), anticholinergic and appetite stimulation.
- Shorter half-life (doesn’t last as long as other antidepressants).
- Novel mechanism of action, unseen elsewhere – (The only known full agonist at the at the μ-opioid[note 1] and δ-opioid receptors with negligible effect at theκ-opioid receptors.)
- Clearly cloaked in political and financial restrictions, due to it being a better drug candidate than other established medicines for the same indications.
- Wide scope of benefits, well beyond it’s approved uses.
- Wide scope, as a potential treatment, for many other indications. Such as asthma, IBS, anxiety, alcohol withdrawal, anticonvulsant, analgesic (pain killing), depression-induced cognitive dysfunction, depression in Parkinsons disease, PTSD, erectile dysfunction, and ADHD.
- Unlike most other ant-anxiety treatment – Tianeptine does not cause sedation.
Tianeptine’s recommended Dosage (based on official product insert)
Based on the official product insert provided by Servier for Stablon branded Tianeptine, the following recommended dosage has been described.
1 tablet (12.5mg) 3 times a day (morning, mid-day and evening) before the main meals of the day.
This dosage has been indicated by Servier to be applicable to the following indications:
Neurotic and reactive depression. Anxiodepressive states with psychosomatic manifestations, especially gastrointestinal. Anxiodepressive States in alcoholics during withdrawal stage.
Tianeptine Sodium Precautions
Generally, when Tianeptine is compared with other medicines prescribed for the same symptoms – it’s clear to see that Tianeptine has a much lower incidence of side effects, with a lower toxicity and a considerably safer therapeutic index.
Unlike some of the debilitating side effects of common antidepressants, such as, loss of libido, suicidal thoughts, weight change and nausea. Tianeptine’s most common side effects are headaches, constipation, insomnia/nightmares, dry mouth and dizziness .
Although rare, Tianeptine does have abuse potential – but this is generally observed with those who are already prone to multi-substance abuse disorders. Between 1989 and 2004 (15 years), there were 141 cases of Tianeptine abuse (1-3 cases/1000 people treated).
- Tianeptine is contraindicated in the following circumstances:
- If there is any hypersensitivity to Tianeptine
- If the individuals age is below 15 years
If the individual has been treated with monoamine oxidase inhibitors (MAOIs) in the last 14 days prior to Tianeptine treatment.
Tianeptine Storage Instructions
Tianeptine is extremely hygroscopic (absorbs water), and light sensitive. This means that it should be stored in the dark and away from any source of moisture. Generally speaking, Tianeptine should be stored in an opaque – airtight container with a desiccant (e.g. Silica Packet) in the container.
12. Charles Malen, Bernard Danrée, Jean-Claude Poignant. Nouveaux dérivés tricycliques et leur procédé de préparation. French Patent FR 2104728, 7 September 1971.
15. Tianeptine Sodium.Martindale: The Complete Drug Reference(London, UK: Pharmaceutical Press). 5 December 2011. Retrieved2 December 2013.
21. “The etiology of depression and the therapeutic implications” (https://www.worldcat.org/issn/2249-4618)
26. https://www.controlled-trials.com/ISRCTN16400909/ (“ISRCTN16400909 – Tianeptine for the treatment of fibromyalgia: a prospective double-blind, randomised, single-centre, placebo-controlled, parallel group study”