Chapter 12

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Bronchial Asthma

The treatment of bronchial asthma with tianeptine, a

drug which enhances the uptake of 5HT from plasma to
platelets has been tested in more than 16,000 patients:
3.125 mg (1/4 tablet) to 12.5 mg (one tablet). We used this
treatment in patients aged from 6 months to 58 years, 2 or
3 times daily during days or weeks. The dose of tianeptine
can be adjusted according to age and severity of symp-
toms. Usually, we administered tianeptine every day dur-
ing 6–10 days. Further, the drug is taken when necessary.
The administration of tianeptine at the beginning of
attacks cut them suddenly. Furthermore, the administra-
tion of tianeptine during attacks provokes suppression
45–60 min after drug ingestion. We have never registered
undesirable side effects. Progressive disappearance of
asthma attacks are observed in all cases.
In 1996, Lechin and coworkers published a paper in
Annals of Allergy, Asthma and Immunology, reporting
findings showing that symptomatic asthma patients have
increased levels of NA, Ad, DA, f5HT and CRT. They
also demonstrated, that f5HT plasma levels but not the
other parameters correlated significantly with clinical se-
verity and, in addition, both f5HT and clinical rating cor-
related negatively with all parameters of pulmonary func-
tioning (FEV1, FVC, etc.). The plasma neurotransmitter
profile registered during symptomatic asthma periods as
well as the increased platelet aggregability they found in
these patients during these periods, are consistent with
the association of asthma attacks with uncoping stress

Fig. 12.1. Graphs show levels of NA, Ad, and DA in symptomatic

asthmatic patients, and control patients at the start of study (week 0)
and at 4-weekly intervals. Mean B SEM. * Symptomatic vs. asymp-
tomatic; +asymptomatic vs. control: p ! 0.005 in all cases [Lechin et
al., Ann Allergy Asthma Immunol 1996;77:245–253].

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Fig. 12.2. Graphs show levels of p5HT and CRT in symptomatic
asthmatic patients, asymptomatic asthmatic patients, and control
patients at the start of the study (week 0) and at 4-weekly intervals.
* Symptomatic vs. asymptomatic; + asymptomatic vs. control: p !
0.005 in all cases. Nonsignificant differences among weeks [Lechin et
al., Ann Allergy Asthma Immunol 1996;77:245–253].
situation. Finally, the association of asthma with uncop-
ing stress situation is consistent with the inclusion of this
disease among the Th-2 autoimmune diseases. Although
the published paper [Lechin et al., 1996] appeared in Sep-
tember 1996, Lechin’s group had previously published
one abstract in Am J Respir Crit Care Med [Lechin AE et
al., 1994].
In 1998, Lechin’s group published two research papers
showing that tianeptine provoked a dramatic and sudden
decrease of both clinical rating and f5HT plasma levels
and an increase in pulmonary functioning [Lechin et al.,
1998a, b]. In addition, there are two other related articles
Bronchial Asthma
Fig. 12.3. Graphs show FEV1, plasma f5HT, and clinical rating in
symptomatic asthmatic patients, asymptomatic asthmatic patients,
and control patients at the start of study (week 0) and at 4-weekly
intervals. Mean values B SEM. * Symptomatic vs. symptomless: p !
0.0001. Nonsignificant differences were registered among weeks [Le-
chin et al., Ann Allergy Asthma Immunol 1996;77:245–253].
dealing with this issue by Cazzola and Matera [2000] and
Lechin F [2000], both published in Trends in Pharmaco-
logical Sciences.
Finally, Dupont et al. [1999] demonstrated that 5HT
facilitates cholinergic contraction in human airways in
vitro through stimulation of both prejunctional 5-HT3
and 5-HT4 receptors. These findings ratified the etiopa-
thogenic role of plasma 5HT in bronchial asthma and, in
addition, strongly suggest that not only 5HT uptake
enhancers but also 5HT3 and 5HT4 antagonists should be
considered as powerful tools in the treatment of this dis-
ease.
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12.4

Fig. 12.4. Regression analysis showing a negative correlation between

FEV1 and f5HT levels in 57 symptomatic patients with asthma [Le-
chin et al., Ann Allergy Asthma Immunol 1996;77:245–253].
Fig. 12.5. Effects of tianeptine in 69 symptomatic patients with asth-
ma, measured in three different parameters: FEV1, clinical severity,
and plasma f5HT. Solid bars = group that received placebo (P) for 4
weeks, tianeptine (T) for 24 weeks, and placebo again for 24 weeks.
White bars = group received placebo for 20 weeks and tianeptine for
32 weeks. During the last 2 months the patients represented by the
white bars did not take oral prednisone. * p ! 0.005 [Lechin et al.,
Clin Pharmacol Ther 1998;64:223–232]. 12.5

Pulmonary Hypertension (1 case), primary pulmonary hypertension (1 case),

Plasma serotonin (f5HT) has found to be raised in pri-
mary pulmonary hypertension [Hervé et al., 1995]. Other
findings demonstrated that fenfluramine, a 5HT-releas-
ing agent, is responsible for pulmonary vasoconstriction.
In addition to the above, Lechin’s group found that sever-
al types of pulmonary hypertension patients – vasculitis
chronic bronchitis (3 cases), chronic asthma (7 cases), and
obesity (1 case) – showing greatly raised f5HT plasma lev-
els were much improved by tianeptine administration
and that clinical improvement paralleled a normalization
of plasma levels [Lechin, 2001; Lechin and van der Dijs,
2002; Lechin et al., 2002]. All the above support the etio-
pathogenic role played by f5HT.

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