Tianeptine

To The Editor

We read with great interest the review article by Boushey (March 2003) (1) dealing with new exploratory therapies lot asthma. with respect to it, we regret that the author omitted the successful results obtained by our research group, referring to the treatment of bronchial asthma with tianeptine. This drug, a serolonin (5-HT) uptake enhancer, triggers absolute and tariff disappearance of asthma attacks within 30 to 60 min after oral intake.

Up to the present, we have successfully treated some 20,000 severe asthmatic (children mad adults) with this drug, without failures. (2) Even more, at the present time we outlined a national program, addressed to eradicate this disease from our country. With respect to the above, we have published many scientific articles dealing with the pathophysiologic mechanisms invoked in the infallibility of this therapeutic manipulation.

In 1994, we presented results dealing with the increasing levels of catecholamines and free-serotonin (f-5HT) in plasma during asthma attacks. (3) In 1996, we demonstrated that increased levels of f-5HT in plasma, during asthma attacks, were associated with clinical severity and pulmonary function. (4) In 1998, we published two research articles showing that tianeptine (a serotonin uptake enhancing drug, which reduces plasma f-5HT) provoked a dramatic and sudden decrease of both clinical rating and f-5HT plasma levels as well as an increase in f-5HT function. (5,6) Conversely, buspirone and serotonin uptake inhibitors (like sertraline, paroxetine, etc), drags that increase f-5HT in plasma, trigger asthma attacks in asthmatic patients. (7-9) These undesirable effects were annulled by atropine. (10)

In 1999, Dupont et al (11) demonstrated that serotonin produced frequency- and concentration-dependent facilitation of cholinergic contractions of human airways. This facilitatory effect of 5-HT was mimicked by both 5-H[T.sub.3] and 5-H[T.sub.4] agonists. These findings demonstrated that 5-HT facilitates cholinergic contractions in the human airways. In 2000, Cazzola and Matera (12) published an article dealing with the role played by 5-HT in asthma and other bronchial disorders. Finally, it has been exhaustively demonstrated that all drags that increase f-5HT plasma levels trigger not only bronchoconstriction but pulmonary vasoconstruction also, both of which are greatly annulled by tianeptine, a drag that decreases f-5HT plasma level. (13-19) With respect to the latter, it should be remembered that acetylcholine stimulates the release of 5HT from the neuroepithelial autocrine serotonergic cells located at the bronchopulmonary system and, in turn, serotonin triggers acetylcholine release from the parasympathetic terminals. (20)

Fuad Lechin, MD, PhD

Bertha van der Dijs, MD

Universidad Central de Venezuela

Caracas, Venezuela

Alex E. Lechin, MD, FCCP

University of Houston

Houston, TX

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestcet.org).

Correspondence to: Alex E. Lechin, MD, FCCP, Department of Clinical Science, University of Houston, 2717 Albany Rd, Houston TX 77005

REFERENCES

(1) Boushey HA. New and exploratory therapies for asthma. Chest 2003; 123(3 Suppl):439S-445S

(2) Lechin F, van der Dijs B, Lechin ME. Bronchial asthma. In: Lechin F, van der Dijs B, Lechin ME, eds. Neurocircuitry and neuroautonomic disorders: reviews and therapeutic strategies. Basel. Switzerland: Karger AG, 2002; 66-68

(3) Lechin AE, Varon J, van der Dijs B, et al. Plasma catecholamines and indoleamines during attacks and remission on severe bronchial asthma: possible role of stress [abstract]. Am J Respir Crit Care Med 1994; 149:A778

(4) Lechin F, van der Dijs B, Orozco B, et al. Increased levels of free-serotonin in plasma of symptomatic asthmatic patients. Ann Allergy Asthma Immunol 1996; 77:245-253

(5) Lechin F, van der Dijs B, Orozco B, et al. Neuropharmological treatment of bronchial asthma with an antidepressant during: tianeptine; a double-blind crossover placebo-controlled study. Clin Pharmacol Ther 1998; 64:223-232

(6) Lechin F, van der Dijs B. Lechin A, et al. The serotonin uptake enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind crossover placebo controlled study. J Clin Pharmacol 1998; 38:918-925

(7) Lechin F, van der Dijs B, Jara H, et al. Effects of buspirone on plasma neurotransmitters in healthy subjects. J Neural Transm 1998; 105:561-573

(8) Lechin F, van der Dijs B, Jackubowicz D. et al. Role of stress in the exacerbation of chronic illness: effects of clonidine administration on blood pressure and plasma norepinephrine, cortisol, growth hormone and pressure concentrations. Psychoneuroendocrinology 1987; 12:117-129

(9) Lechin V, van der Dijs B, Orozco B. et al. Plasma neurotransmitters, blood pressure and heart rate during supine resting, orthostasis and moderate exercise in severely ill patients: a model of failing to cope with stress. Psychother Psychosom 1996; 65:129-1:36

(10) Lechin F, van der Dijs B, Orozco B, et al. Plasma neurotransmitters, blood pressure and heart rate during supine-resting, orthostasis and moderate exercise stress test in healthy humans before and after parasympathetic blockade with atropine. Pine. Res Comm Biol Psychol Psychiatry 1996; 21:55-7911

(11) Dupont LJ, Pype JL, Dernedts MG, et al. The effects of 5-HT on cholinergic contraction in human airways in vitro. Eur Respir J 1999; 14:642-649

(12) Cazzola M, Matera MG. 5-HT modifiers as a potential treatment of asthma. Trends Pharmacol Set 2000; 21:13-16

(13) Lechin F, van der Dijs B. Serotonin and pulmonary vasoconstriction [letter]. J Appl Physiol 2002; 92:1363-1364

(14) Lechin F, van der Dijs B, Lechin AE. Pulmonary hypertension, left ventricular dysfunction and plasma serotonin [letter]. Br J Pharmacol 2002; 137:937-9:38

(15) Lechin F. Asthma, asthma medication and autonomic nervous system dysfunction [letter]. Clin Physiol 2001; 6:723

(16) Lechin F, van der Dijs B. Lechin AE. Serotonin, pulmonary hypertension and bronchial asthma [letter]. Clin Set 2002; 103:345-346

(17) Lechin F. Central and plasma 5-HT, vagal tone and airways [letter]. Trends Pharmacol Sci 2000; 21:425

(18) Lechin F. van der Dijs B, Lechin AE. Severe asthma and plasma serotonin [letter]. Allergy 2002; 57:258-259

(19) Lechin F, van der Dijs B, Lechin AE. Tianeptine, plasma serotonin and pulmonary hypertension [letter]. Lancet 2003; 361:87

(20) Cattaneo MG, Codignola A, Vicentini LM, et al. Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma. Cancer Res 1993; 53:5566-5568

To the Editor:

I have carefully reviewed the letter from Drs. Lechin and van der Dijs and the literature that they cite. Of the citations, only two are to articles describing trials of asthma therapy that were published in peer-reviewed journals (their refs 5, 6). These two articles were published within 4 months of each other, have identical authors, describe findings from the same intervention in the same number of subjects, and have abstracts that read nearly identically. The two articles appear to describe the same study.

Of the remaining references, seven appear not to deal directly with asthma (refs 7-10, 14, 19, 20), seven are letters to the editor (refs 13-18), one is an abstract (ref 3), and one is a book authored by Drs. Lechin and van der Dijs (ref 2). I cannot comment on their use of tianeptine in 20,000 patients with severe asthma, nor on its use in a national program to eradicate the disease in their country, for the hook that they trite is not yet available to me. I am sure, however, that Drs. Lechin and van der Dijs would want to share with the rest of the medical world a treatment for asthma unfailingly successful. The usual way to share such information is through publishing in peer-reviewed journals large, controlled, prospective, blinded studies demonstrating efficacy. For such a remarkably, effective treatment, this should be easy to accomplish, I, for one, would read such reports with the keenest interest.

Homer A. Boushey, MD

University of California San Francisco

San Francisco, CA

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Homer A. Boushey, MD, University of California San Francisco Division of Allergy and Immunology 505 Parnassus Ave, M-1292, San Francisco, CA 94143

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