What is tianeptine?

Discovered and patented by the French Society of Medical Research in the 1960s, Tianeptine is available in a number of European, Asian, and Latin American countries. But the drug that is used primarily in the treatment of clinical depression is not prescribed in Canada, the U.K., the U.S., Australia, and New Zealand. One of the reasons for its limited availability is, once again, that Tianeptine does not fit neatly into any known class of antidepressants. In fact, it was mislabeled as an selective serotonin reuptake enhancer (SSRE) until only recently. We also know that tianeptine has disparate chemical and pharmacological properties that have left researchers scratching their proverbial heads as to how the drug produces its antidepressant effects. One thing we know for certain, however, is that tianeptine works, and works well!

How well it works

As the most widely used tricyclic (TCA) antidepressant, amitriptyline is on the World Health Organization’s List of Essential Medicines. Approved for use in 1961, it has been a benchmark for all other drugs in its class ever since. In fact, many researchers believe that amitriptyline may have superior efficacy than many, even most, SSRIs and SNRIs in treating major depressive episodes. It is surprising then that tianeptine compares favorably to the popular pill in many key areas.

Researchers may not know how it works, but tianeptine’s efficacy against major depression has never been in doubt. Compared to amitriptyline, imipramine, maprotiline, and other TCAs, tianeptine has significantly fewer side effects. It even stacks up well against fluoxetine (a.k.a. Prozac), the most widely prescribed SSRI.

One advantage tianeptine has over most other antidepressants is its remarkable anxiolytic properties. This is important because anxiety is one of the most common symptoms of clinical depression. As result, tianeptine has proven effective at treating a wide spectrum of anxiety disorders that are often involved in major depressive episodes, including panic and post-traumatic stress disorders.

Tianeptine may also have a beneficial effect on cognition, due in part to its relative lack of sedative qualities. According to numerous studies, drowsiness was a fairly uncommon side effect of the medication. Tianeptine has also compared favorably to other antidepressants in tolerability tests, where subjects consistently reported fewer and less intense adverse effects of sustained treatment.

Medical benefits

There are several reasons why tianeptine is not considered a first-line antidepressant. To begin with, it belongs to an older class of drugs (TCAs) that generally have a higher risk toxicity in overdose and lower tolerability than newer medications in SSRI and SNRI drug classes. Secondly, it is not sold in many countries. It is this last fact that is particularly puzzling, since many clearly inferior drugs in its class are widely available. As we mentioned earlier, tianeptine have proven every bit as efficacious against major depressive episodes as amitriptyline (the most popular tricyclic antidepressant), but with significantly fewer side effects. The drug even has advantages over SSRIs and SNRIs, for which hundreds of millions of prescriptions are dispensed each year in America. Such as?

As popular as they may be, it is well established that serotonin enhancers (SSRIs and SNRIs) cause problems in the bedroom. Diminished libido, delayed sexual arousal, and muted or absent orgasm are common symptoms of these prescription medications. Because it does not affect serotonin levels directly, taking tianeptine will not cause adverse sexual side effects. In fact, there is some evidence that sexual function could actually be enhanced by the combination of non-stimulating mood brightener and non-sedative anti-anxiety agents. Why then is tianeptine so much harder to find?

Contrary to rumors on the internet, there is no conspiracy that has kept the drug from those in need, wherever they might reside. The real reason tianeptine is not sold in some countries is because the companies that manufacture it have decided not to enter certain markets, mostly likely because the costs of entry is prohibitive. With that said, there are many in the psychiatric community that believe the time-tested psychotropic drug could help millions were it more widely available.

Who should take it?

Because it does not cause sedation or sleeping problems, tianeptine is suitable for patients who are sensitive to the unwanted effects of most antidepressants, including the elderly and those recovering from alcohol withdraw. The drug could also be of great benefit to those who suffer from anxiety disorders. How?

At last count, forty million American adults struggled with some form of anxiety on a regular basis. About one-third of those that seek treatment also report regular bouts of depression, since the two disorders are highly correlated with each other. In other words, those who are depressed are often anxious and vice versa. And since tianeptine is both a antidepressant and an anxiolytic, it can be used to treat both illnesses simultaneously.

Why it works

Although recent discoveries have provided some much-needed insight, researchers have merely scratched the surface when it comes to the complicated series of chemical reactions tianeptine intake triggers in the brain. At its simplest level, we know that unchecked stress causes the adrenal glands to secrete a surfeit of cortisol, a powerful stress hormone. The primary function of this steroid is to increase blood sugar and give the body the energy and strength it needs to defend itself from danger. Also known as the fight-or-flight response or the stress reaction, this involuntary process tends to lower mood levels in order to help us focus on the task at hand. But when cortisol and other stress hormones remain at elevated levels for protracted periods of time, they can cause clinical depression. In fact, cortisol levels are now used as a biological marker for suicide risk.

Current evidence strongly suggests that tianeptine works to prevent and even reverse the neural damage that is caused by stress or stress hormones like cortisol. Researchers also believe that continued use of the drug may help normalize the hypothalamic-pituitary-adrenal (HPA) system, which is responsible for monitoring and releasing cortisol and other stress hormones. In other words, tianeptine may help at-risk individuals deal with stressful environments and situations a bit better by normalizing their HPA system.


As with many psychotropic medications, tianeptine won’t work for everyone: research shows that perhaps as much as one-third of users do not respond as expected. With that said, tianeptine has proven efficacious in antidepressant cocktails when monotherapy, or use of a single first-line drug, has failed. Most promising of all is the drug’s apparent ability to protect against and even reverse the effects of hypercortisolemia – a condition that results from prolonged exposure to excessive cortisol levels, and one that is strongly linked to major depressive episodes. Long-term use of tianeptine may therefore protect against relapse and recurrence of clinical depression.

At the end of the day, depressive illness is an incredibly complex disorder that we may never fully understand. What we do know, however, is that the more tools we have to fight melancholia, the more hope we can offer those who suffer its devastating effects. Tianeptine may not be the catholicon its supporters suggest, but what it has to offer is both valuable and unique. An established mood-brightener-cum-anti-anxiety medication that is well tolerated and relatively safe, tianeptine’s neglect by the Anglo-American psychiatric community is shortsighted and undeserved.