Major depression is one of the most common mental disorders in the population, and the search for therapeutic alternatives for its treatment is of great importance. The use of psychotropic drugs is one of these alternatives, many substances being classified as antidepressants and having among them mechanisms of action that may differ to a greater or lesser extent.

Some of these substances may even have an effect through a mechanism of action that may seem contrary to that of most of these types of drugs. This is what happens with thianeptin , which we will discuss in this article.

What is thianeptin

Thianeptin is a psychoactive drug synthesized in the 1970s, which was created to combat depressive symptoms. This antidepressant has interesting properties , and has been shown to have a level of effectiveness similar to that of substances such as fluoxetine, also presenting a rapid action by having the first effects about one or two weeks after the first consumption (usually, antidepressants take about a month). It has also been used as an adjuvant treatment to improve the effectiveness of other antidepressants, as well as other disorders such as anxiety and stress.

It has sometimes been classified as tricyclic because it has the same chemical structure, but the truth is that its mechanism of action does not correspond to that of this group. In fact, it could rather be classified differently in a new category: due to its mechanism of action, opposed to that of the specific serotonin reuptake inhibitors or SSRIs, thianeptin is the main representative of the serotonin reuptake enhancers or PSRSs .

Despite its effectiveness and usefulness, thianeptin is often not particularly well known or used because it has a relatively high risk of generating dependence (even being classified as a narcotic drug in countries such as France), not being authorized as an antidepressant in many countries as the balance between risks and benefits was considered to be at best slightly favourable. However, if it is sold in other ways, because has nootropic effects and improves memory . In our country, it has begun to be marketed as an antidepressant in 2015, but other alternatives are usually used as first-line treatment.

Mechanism of action

Thianeptin is a unique antidepressant because of its peculiar mechanism of action. Unlike popular antidepressants like SSRIs, which inhibit the reuptake of serotonin in such a way that it increases the amount of this hormone in the brain, thianeptin works by greatly enhancing this reuptake.

Although it may seem that this mechanism of action is counterproductive, the truth is that thianeptin is effective in the treatment of depressive symptoms. Despite the fact that the amount of serotonin present in the synaptic space is recaptured, it also seems to act by intensifying communication between neurons in the serotonergic pathways . The drug itself does not appear to bind to any receptors.

It also reduces levels of ACTH and glucocorticoids, which makes it useful in fighting stress. It also reduces the activity of the hypothalamic-pituitary-adrenocortical axis. It also contributes to increase the levels of acetylcholine in the brain (among other reasons because it reduces the level of serotonin). Finally, also seems to modify the functioning and transmission of glutamate , normalizing itself in situations of stress.

Applications and indications

Thianeptin is a psychoactive drug that has been used in different disorders and with different applications. The first and most notable is its indication in major depression and other depressive disorders, in which, as mentioned, it has an effectiveness comparable to that of such popular drugs as SSRIs.

It is also very useful in the treatment of anxiety disorders and even somatic type disorders, having no negative effect on the level of consciousness. It has been shown to be very useful in the treatment of stress, also preserving from damage derived from its continuous experience in areas such as the hypothalamus.

Finally, thianeptin is also marketed as a dietary supplement in some countries because of its ability to facilitate increased levels of acetylcholine, which promotes attention and learning and facilitates memorization and recall.

Side effects and contraindications

Thianeptin is a drug with a considerable level of efficacy. Unlike other drugs, it does not cause sexual dysfunction or increase weight. It has not been detected to generate arrhythmias or heart problems, and it is especially known that it does not generate drowsiness. However, its consumption can generate different side effects.

Among the side effects we can find, thianeptin could generate vertigo and dizziness, tremor, abdominal pain, headache and cold symptoms . Also asthmatic crises, anorexia or loss of appetite, pains, palpitations, tachycardia, suffocation and asthenia. In subjects with a history of psychotic outbreaks it may facilitate their reappearance. Likewise, one of the great risks of this drug is that it has a great potential to generate dependency, and the subject who consumes it may become addicted. This is one of the main factors why its use has not become popular and in fact it is not marketed in different countries.

The main contraindications are that should not be taken by subjects who are taking MAOI-type antidepressants , or before the application of an anaesthetic. It is also contraindicated in subjects with addiction problems (although it is used in depressions with alcoholism), subjects with positive psychotic symptoms and/or manic episodes. Great caution should be taken by pregnant women, nursing mothers or minors, as well as people with kidney problems.

Bibliographic references

  • McEwen, B.S.; Chattarji, S.; Diamond, D.M.; Jay, T.M.; Reagan, L.P.; Svenningsson, P. & Fuchs, E. (2010). The neurobiological properties of Tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. Mol Psychiatry; 15(3): 237-49. doi:10.1038/mp.2009.80.
  • Watanabe, Y.; Gould, E.; Daniels, D.C.; Cameron, H. & McEwen, B.S. (1992). Tianeptine attenuates stress-induced morphological changes in the hippocampus. European Journal of Pharmacology; 222: 157-16.
  • Calabozo, B.; Molina, V. & Uribe, F. (2016). Tianeptin: why it has not been classified as a narcotic in Spain. Psychiatry, Health ;ent; 9 (3): 176-177.