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Evident exception in clinical practice not sufficient to break traditional hypothesis

Posted by plosmedicine on 30 Mar 2009 at 23:49 GMT

Author: Milan Sarek
Position: MD
Institution: Psychiatric Department, Charles University in Prague
Submitted Date: December 19, 2005
Published Date: December 29, 2005
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

I read with interest the article written by Jeffrey R. Lacasse and Jonathan Leo (1). They have found that pharmaceuticals companies marketing selective serotonin reuptake inhibitors (SSRIs) in the United States commonly declare that SSRIs correct chemical imbalance in depression caused by a lack of serotonin. The authors argue that serotonin deficiency in depression is scientifically unsupportable and, therefore, statements about the lack of serotonin should not be used.

I agree with the authors. Nevertheless, I would like to add information about another example of drug for supporting their arguments. I consider that this drug should be mentioned in every article describing serotonin system and depression. The drug is not authorized in English speaking countries (2) and this may possibly explain why the information about its controversial mechanism is not largely shared in scientific literature.

The name of this drug is tianeptine. It has been used over decade in several European and other countries to relieve depression. Tianeptine increases serotonin reuptake and therefore has the opposite action on the serotonin system to that of SSRIs (2,3,4). The antidepressant efficacy of tianeptine versus tricyclics and SSRIs has been demonstrated in several studies (3,4). Because of this opposite action on the serotonin system, it has a different adverse event profile; e.g. the elevated frequency of sexual dysfunction commonly seen after SSRIs is not so frequently observed with tianeptine (5).

The mechanism of tianeptine's action is difficult to understand but it comparison of the drug with other antidepressants provides us with an intellectual challenge(6).

Tianeptine has been in clinical use for over 12 years in our country, but statements about serotonin deficiency in depression are still presented to public by the media and in the patient information leaflets accompanying the majority of registered SSRIs. One of the reasons for this may be that it is difficult for the single producer of tianeptine to argue against the 'traditional' hypothesis that supports the numerous leading pharmaceutical companies that market SSRIs.

For these reasons I propose that the most direct way to conquer the unsupportable, but widely proclaimed, concept of serotonin deficiency in depression would be to act through regulatory authorities which have the responsibility for the information given to public, and also have the power to change the information that is provided about registered drugs.


1) Jeffrey R. Lacasse, Jonathan Leo. Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med. 2005;2(12):e392
2) MICROMEDEX(R) Healthcare Series Vol. 126 expires 12/2005.
3)Wagstaff AJ, Ormrod D, Spencer CM. Tianeptine: a review of its use in depressive disorders. CNS Drugs. 2001;15(3):231-59
4 Kasper S, Olie JP. A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression. Eur Psychiatry. 2002 Jul;17 Suppl 3:331-40.
5) Bonierbale M, Lancon C, Tignol J. The ELIXIR study: evaluation of sexual dysfunction in 4557 depressed patients in France. Curr Med Res Opin. 2003;19(2):114-24.
6) McEwen BS, Olie JP. Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine. Mol Psychiatry. 2005;10(6):525-37.

No competing interests declared.