Tianeptine: New description of the mechanism of action and change of technical data sheet

Dear Editor:

We are very pleased to be able to inform you of the positive effect a recently published article in the journal “Revista de Psiquiatría y Salud Mental” has had on our clinical practice.

The article Tianeptine, an atypical pharmacological approach to depression, by professor Alamo et al.,¹ is a historical review of antidepressant medication which then focuses on tianeptine, an antidepressant which is classified as atypical because it does not fit into any of the major pharmacological groups of this type of medicine.

Tianeptine has recently been marketed in Spain (2015), although it had already been marketed in the 1990’s in other European countries. At that time, the hypothesis expounded was that tianeptine was a tricyclic antidepressant (but different to the traditional ones), with a serotoninergic mechanism of action.² However, thanks to the advance of research techniques over the last few years in the field of neuropsychopharmacology, this hypothesis has had to be recently modified due to numerous articles which were published after its authorisation and they have had to advance in the knowledge of its mechanism of action and pathways where it exercises its antidepressant effect and other effects, such as anxiolytical and improvement in cognitive function, and which is magnificently summarized in the before-mentioned article.

The first key to the article of Alamo et al. was to clarify that although tianeptine has a heterocyclic structure, with 3 cycles, it cannot be classified as an antidepressant of the tricyclic pharmacological group due to its clear structural differences which present both in the actual rings and in the lateral chain, that distinguish it from other antidepressants. This structure conditions its pharmacological and clinical profile, which is differential to other antidepressants.

The essential part of this cited article is dedicated to the review and updating of all the new evidence resulting from experimental studies and published in recent years on tianeptine and its pharmacological idiosyncrasies. It demonstrates the enormous data processing work performed with the 127 references included in the article, the analysis of which leads to the conclusion that the action of tianeptine is essentially based on the modulation of glutamatergic functionalism. Experimental knowledge of this system is advancing rapidly and today we are aware that apart from its involvement in depression it also participates in other cognition and memory functions. From a clinical perspective the characteristic of tianeptine of presenting an antidepressant action, is accompanied by an additional anxiolytic effect, without provoking sedation and an improvement in cognitive component.

Apart from the scientific dissemination achieved thanks to the article by Alamo et al., advances in the knowledge of tianeptine’s mechanism of action has had a “normative” effect. Thus, last September the Spanish Medicines and Health Products Agency authorised an updating of the technical data sheet of the product Zinosal® (the only drug to contain tianeptine in Spain). In its new version³ the technical data sheet currently describes that “tianeptine is an antidepressant with a glutamatergic mechanism of action”, correcting the existing error in the previous version of the technical data sheet which mentioned that “tianeptine is a tricyclic antidepressant.

As a result, analysis of new accumulated scientific evidence has coincided in time in the form of scientific communication in a Spanish journal (and in Spanish) with a regulatory change that reflects the viewpoint of the health authority.

We believe that it also results in a patient benefit, since Spanish doctors now have greater knowledge of the pharmacological mechanisms of tianeptine, since when it acts with a glutamatergic modulator that is different to the other antidepressants up until now available there is a new perspective in the Spanish antidepressant arsenal. This is a promising event in several situations (e.g. in the case of patients who lack the benefit of other antidepressants or those who may have the added benefit of it providing an additional anxiolytic effect.

Conflict of interests

Both Jaime Algorta (medical director) and Aurora Dominguez (records director) work for Exeltis Healthcare SL, the laboratory which markets tianeptine in Spain.

The authors received no specific financing for this manuscript.