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Communications to the Editor |

Tianeptine : A New Exploratory Therapy for Asthma FREE TO VIEW

Fuad Lechin; Bertha van der Dijs; Alex E. Lechin
Author and Funding Information

Affiliations: Universidad Central de Venezuela, Caracas, Venezuela,  University of Houston, Houston, TX,  University of California San Francisco, San Francisco, CA

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



Chest. 2004;125(1):348-349. doi:10.1378/chest.125.1.348
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To The Editor:

We read with great interest the review article by Boushey (March 2003)1 dealing with new exploratory therapies for 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 serotonin (5-HT) uptake enhancer, triggers absolute and total 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 and 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 involved 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 pulmonary function.56 Conversely, buspirone and serotonin-uptake inhibitors (like sertraline, paroxetine, etc), drugs that increase f-5HT in plasma, trigger asthma attacks in asthmatic patients.79 These undesirable effects were annulled by atropine.10

In 1999, Dupont et al11 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-HT3 and 5-HT4 agonists. These findings demonstrated that 5-HT facilitates cholinergic contractions in the human airways. In 2000, Cazzola and Matera12 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 drugs that increase f-5HT plasma levels trigger not only bronchoconstriction but pulmonary vasoconstriction also, both of which are greatly annulled by tianeptine, a drug that decreases f-5HT plasma level.1319 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

References

Boushey, HA (2003) New and exploratory therapies for asthma.Chest123(3 Suppl),439S-445S
 
Lechin, F, van der Dijs, B, Lechin, ME Bronchial asthma. Lechin, F van der Dijs, B Lechin, ME eds.Neurocircuitry and neuroautonomic disorders: reviews and therapeutic strategies.2002,66-68 Karger AG. Basel, Switzerland:
 
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
 
Lechin, F, van der Dijs, B, Orozco, B, et al Increased levels of free-serotonin in plasma of symptomatic asthmatic patients.Ann Allergy Asthma Immunol1996;77,245-253. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B, Orozco, B, et al Neuropharmacological treatment of bronchial asthma with an antidepressant drug: tianeptine; a double-blind crossover placebo-controlled study.Clin Pharmacol Ther1998;64,223-232. [CrossRef] [PubMed]
 
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 Pharmacol1998;38,918-925. [PubMed]
 
Lechin, F, van der Dijs, B, Jara, H, et al Effects of buspirone on plasma neurotransmitters in healthy subjects.J Neural Transm1998;105,561-573. [CrossRef] [PubMed]
 
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 prolactin concentrations.Psychoneuroendocrinology1987;12,117-129. [CrossRef] [PubMed]
 
Lechin, F, 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 Psychosom1996;65,129-136. [CrossRef] [PubMed]
 
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.Res Comm Biol Psychol Psychiatry1996;21,55-72
 
Dupont, LJ, Pype, JL, Dernedts, MG, et al The effects of 5-HT on cholinergic contraction in human airwaysin vitro.Eur Respir J1999;14,642-649. [CrossRef] [PubMed]
 
Cazzola, M, Matera, MG 5-HT modifiers as a potential treatment of asthma.Trends Pharmacol Sci2000;21,13-16. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B Serotonin and pulmonary vasoconstriction [letter].J Appl Physiol2002;92,1363-1364. [PubMed]
 
Lechin, F, van der Dijs, B, Lechin, AE Pulmonary hypertension, left ventricular dysfunction and plasma serotonin [letter].Br J Pharmacol2002;137,937-938. [CrossRef] [PubMed]
 
Lechin, F Asthma, asthma medication and autonomic nervous system dysfunction [letter]. Clin Physiol. 2001;;6 ,.:723
 
Lechin, F, van der Dijs, B, Lechin, AE Serotonin, pulmonary hypertension and bronchial asthma [letter].Clin Sci2002;103,345-346. [PubMed]
 
Lechin, F Central and plasma 5HT, vagal tone and airways [letter]. Trends Pharmacol Sci. 2000;;21 ,.:425. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B, Lechin, AE Severe asthma and plasma serotonin [letter].Allergy2002;57,258-259. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B, Lechin, AE Tianeptine, plasma serotonin and pulmonary hypertension [letter]. Lancet. 2003;;361 ,.:87
 
Cattaneo, MG, Codignola, A, Vicentini, LM, et al Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma.Cancer Res1993;53,5566-5568. [PubMed]
 

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 710,, 14,, 19,, 20 ), seven are letters to the editor (refs 1318 ), 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 book that they cite 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.


Figures

Tables

References

Boushey, HA (2003) New and exploratory therapies for asthma.Chest123(3 Suppl),439S-445S
 
Lechin, F, van der Dijs, B, Lechin, ME Bronchial asthma. Lechin, F van der Dijs, B Lechin, ME eds.Neurocircuitry and neuroautonomic disorders: reviews and therapeutic strategies.2002,66-68 Karger AG. Basel, Switzerland:
 
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
 
Lechin, F, van der Dijs, B, Orozco, B, et al Increased levels of free-serotonin in plasma of symptomatic asthmatic patients.Ann Allergy Asthma Immunol1996;77,245-253. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B, Orozco, B, et al Neuropharmacological treatment of bronchial asthma with an antidepressant drug: tianeptine; a double-blind crossover placebo-controlled study.Clin Pharmacol Ther1998;64,223-232. [CrossRef] [PubMed]
 
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 Pharmacol1998;38,918-925. [PubMed]
 
Lechin, F, van der Dijs, B, Jara, H, et al Effects of buspirone on plasma neurotransmitters in healthy subjects.J Neural Transm1998;105,561-573. [CrossRef] [PubMed]
 
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 prolactin concentrations.Psychoneuroendocrinology1987;12,117-129. [CrossRef] [PubMed]
 
Lechin, F, 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 Psychosom1996;65,129-136. [CrossRef] [PubMed]
 
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.Res Comm Biol Psychol Psychiatry1996;21,55-72
 
Dupont, LJ, Pype, JL, Dernedts, MG, et al The effects of 5-HT on cholinergic contraction in human airwaysin vitro.Eur Respir J1999;14,642-649. [CrossRef] [PubMed]
 
Cazzola, M, Matera, MG 5-HT modifiers as a potential treatment of asthma.Trends Pharmacol Sci2000;21,13-16. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B Serotonin and pulmonary vasoconstriction [letter].J Appl Physiol2002;92,1363-1364. [PubMed]
 
Lechin, F, van der Dijs, B, Lechin, AE Pulmonary hypertension, left ventricular dysfunction and plasma serotonin [letter].Br J Pharmacol2002;137,937-938. [CrossRef] [PubMed]
 
Lechin, F Asthma, asthma medication and autonomic nervous system dysfunction [letter]. Clin Physiol. 2001;;6 ,.:723
 
Lechin, F, van der Dijs, B, Lechin, AE Serotonin, pulmonary hypertension and bronchial asthma [letter].Clin Sci2002;103,345-346. [PubMed]
 
Lechin, F Central and plasma 5HT, vagal tone and airways [letter]. Trends Pharmacol Sci. 2000;;21 ,.:425. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B, Lechin, AE Severe asthma and plasma serotonin [letter].Allergy2002;57,258-259. [CrossRef] [PubMed]
 
Lechin, F, van der Dijs, B, Lechin, AE Tianeptine, plasma serotonin and pulmonary hypertension [letter]. Lancet. 2003;;361 ,.:87
 
Cattaneo, MG, Codignola, A, Vicentini, LM, et al Nicotine stimulates a serotonergic autocrine loop in human small-cell lung carcinoma.Cancer Res1993;53,5566-5568. [PubMed]
 
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