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The paradox of tianeptine

Published online by Cambridge University Press:  16 April 2020

M Ansseau
M Ansseau*
Affiliation:
Psychiatric Unit, CHU du Sort Tilman, B 35 - 4000 Liège l, Belgium
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Summary

The classical biochemical hypothesis of depression posits a functional deficit in central neurotransmitter systems, particularly serotonin (5-HT) and/or noradrenaline. The major support for this theory was that antidepressants increase the amount of neurotransmitters in the synaptic cleft, by inhibiting reuptake mechanisms (tricyclics) or inhibiting enzymatic catabolism (MAOIs). The major role suggested for 5-HT in this theory led to the development of a large number of compounds which selectively inhibit 5-HT reuptake, such as fluvoxamine, fluoxetine, citalopram, sertraline, paroxetine, etc. Numerous clinical studies have demonstrated the antidepressant activity of such types of agents, supporting 5-HT deficit as the main origin of depression. Tianeptine is active in classical animal models of antidepressants. Its antidepressant efficacy has been established in controlled trials involving a large number of patients. Several biochemical studies however demonstrated that tianeptine induces in acute as well as in chronic conditions, a presynaptic increase of 5-HT reuptake, both in animal and human platelets and animal CNS. Therefore, as a 5-HT reuptake enhancer, tianeptine exhibits a mechanism of action totally opposite to 5-HT reuptake blockers such as fluoxetine but, paradoxically, both mechanisms of action are associated with a therapeutic activity in depressive disorders. Several hypotheses to explain these paradoxical findings and different methodologies to test them clinically are proposed.

Keywords

tianeptineantidepressantserotoninselective serotonin reuptake inhibitor
Type
Research Article
Information
European Psychiatry , Volume 8 , Issue S2: Neuroendocrinological aspects of depression 28 June 1992, Nice, France , 1993 , pp. 89s - 93s
Copyright
Copyright © Elsevier, Paris 1993

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References

Ansseau, M (1988) Les antidépresseurs. Méd et Hvq 46,2314–2321Google Scholar
Ansseau, M (1991) Biological markers of depression: State of the art. In: Biological Markers of Depression: State of the art(Ansseau, Mvon Frenckell, RFranck, G eds). Excerpta Medica, Amsterdam, 1–10Google Scholar
Aprison, MHHintgen, JNNagayama, H (1982) Testing a new theory of depression with an animal model: neurochemical-behavioral evidence for postsynaptic serotonergic receptor involvement. In: New Vistas in Depression (Langer, SZTakahashi, RSegawa, TBriley, M eds). Pergamon, New York, 171–178Google Scholar
Barbaccia, MLGandolfi, OChuang, DMCosta, E (1983) Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.Proc Natl Acad Sci USA 80, 5134–5138CrossRefGoogle ScholarPubMed
Bersani, GPasini, ABrancato, TValducci, MCiani, N (1989) Serotonina e depressione: studio multicentrico controllato tianeptina versus amitriptilina. XXXVII Congresso Nazionale della Societa Italiana di Psychiatria - Roma 6-11 febbraio 1989. CIC Edizioni Intemazionali, 1243–1249Google Scholar
Boyer, WFFeighner, JP (1991) The efficacy of selective serotonin re-uptake inhibitors in depression. In: Selective Serotonin Re-uptake Inhibitors (Feighner, JPBoyer, WF eds). Wiley, Chichester, 89–108Google Scholar
Bunney, WEDavis, JM (1965) Norepinephrine in depressive reactions. Arch Gen Psychiatry 13, 483–494CrossRefGoogle ScholarPubMed
Bunney, WE JrPost, RMAndersen, AEKopanda, RTA (1977) A neuronal receptor sensitivity mechanism in affective illness (a review of evidence). Commun Psychopharmacol 1, 393–406Google Scholar
Carlsson, ACorrodi, HFuxe, KHökfelt, T (1969) Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4- methyl-alpha-ethyl-metatyramine. Eur J Pharmacol 5, 357–366CrossRefGoogle Scholar
Chamba, GLemoine, PFlachaire, EFerry, NQuincy, CSassard, JFerber, CMocaër, EKamoun, ARenaud, B (1991) Increased serotonin platelet uptake after tianeptine administration in depressed patients. Biol Psychiatry 30, 609–617CrossRefGoogle ScholarPubMed
Den Boer, JAWestenberg, HGM (1988) Effect of a serotonin and noradrenaline uptake inhibitor in panic disorder: a double-blind comparative study with fluvoxamine and maprotiline. Int Clin Psvchopharmacol 3, 59–74CrossRefGoogle ScholarPubMed
De Simoni, MGDe Luigi, AClavenna, AManfridi, A(1992) In vivo studies on the enhancement of serotonin uptake by tianeptine. Brain Res 574, 93–97CrossRefGoogle ScholarPubMed
Fattacini, CMBolanos-Jimenez, FGozlan, HHamon, M (1990) Tianeptine stimulates uptake of 5-hydroxytryptamine in vivo in the rat brain. Neuropharmacology 29, 1–8CrossRefGoogle Scholar
Fuller, RWPerry, KWMolloy, BB (1974) Effect of an uptake inhibitor on serotonin metabolism in rat brain: studies with 3-(p-trifluoromethylphenoxy)-N methyl- 3-phenylpropylamine (Lilly 110140). Life Sci 14, 1161–1171CrossRefGoogle Scholar
Guelfi, JDPichot, PDreyfus, JF (1989) Efficacy of tianeptine in anxious-depressed patients. Results of a controlled multicenter trial versus amitriptyline. Neuropsvchobiology 22, 41–48CrossRefGoogle ScholarPubMed
Hamon, MBourgoin, SGozlan, H (1989) Effets de la tianeptine sur la libération in vitro de [3H] 5-HT et sur les divers types de récepteurs sérotoninergiques dans le systéme nerveux central chez le rat. J Psychiatr Biol Thér N° special mars, 48–51Google Scholar
Johnson, AM (1991) The comparative pharmacological properties of selective serotonin re-uptake inhibitors in animals. In: Selective Serotonin Re-uptake Inhibitors (Feighner, JPBoyer, WF eds). Wiley, Chichester, 37–70Google Scholar
Kato, GWeitsch, AF (1988) Neurochemical profile of tianeptine, a new antidepressant drug. Clin Neuropharmacol 11 (suppl 2), S43–S50Google ScholarPubMed
Lôo, HMalka, RDefrance, RBarrucand, DBenard, JYNiox-Riviere, HRaab, ASarda, AVachonfrance, GKamoun, A (1988) Tianeptine and amitriptyline: controlled double-blind trial in depressed alcoholic patients. Neuropsychobiology 19, 79–85CrossRefGoogle ScholarPubMed
Maas, JWFawcett, JDekimenjian, H (1968) 3-melhoxy- 4-hydroxy-phenylglycol (MHPG) excretion in depressive patients. Arch Gen Psychiatry 19, 129–134CrossRefGoogle Scholar
Mennini, TMocaer, EGarattini, S (1987) Tianeptine, a selective enhancer of serotonin uptake in rat brain. Naunvn Schmietleberg's Arch Pharmacol 336, 478–482CrossRefGoogle Scholar
Mocaёr, EKamoun, A (1988) Pharmacological antidepressive effects and tianeptine-induced 5- HT uptake increase. Clin Neuropharmacol 11 (suppl 2), S32–S42Google Scholar
Nagayama, HHinntgen, JNAprison, MH (1980) Prcand postsynaptic serotonergic manipulations in an animal model of depression. Pharmacol Biochem Behav 13,575–579CrossRefGoogle Scholar
Ortiz, JMocaёr, EArtigas, F (1991) Effects of the antidepressant drug tianeptine on plasma and platelet serotonin concentration in the rat. Eur J Pharmacol 199,335–339CrossRefGoogle Scholar
Ostaptzeff, G (1981) É tude contrÔlée à double insu versus imipramine de l'efficacité de la tianeptine dans les états dépressifs ou psychotiques (Perris, CStruwe, GJansson, B eds). Biological Psychiatry. Elsevier/North-Holland Biomedical Press, Amsterdam New York Oxford. Proceedings of the Third World Congress of Biological Psychiatry, Stockholm, June 28/July 3, 1981,597–600Google Scholar
Poignant, JC (1981) Étude pharmacologique d'un nouvel antidepresseur: la tianeptineIn: Biological Psychiatry 1981. Proceedings of the Illrd World Congress of Biological Psychiatry June 28/July 3, 1981 Stockholm, Sweden. Elsevier/North-Holland, 573-578Google Scholar
Quitkin, FMRabkin, JGRoss, DMc Grath, PJ (1984) Duration of antidepressant drug treatment. What is an adequate trial? Arch Gen Psychiatry 41, 238–245CrossRefGoogle ScholarPubMed
Reyntjens, AGelders, YGHoppenbrouwers, MLVanden Bussche, G (1986) Thymosthenic effects of ritanserin (R55 667), a centrally acting serotonin S2 receptor blocker. Drug Dev Res 8, 205–211CrossRefGoogle Scholar
Schildkraut, JJ (1965) The catecholamine hypothesis of affective disorder: a review of supporting evidence. Am J Psychiatry 122, 509–522CrossRefGoogle Scholar
van Praag, HM (1982a) The significance of biological factors in the diagnosis of depressions: I. Biochemical variables. Comp Psychiatry 23, 124–135CrossRefGoogle Scholar
van Praag, HM (1982b) Depression, suicide and metaboThe paradox of lianeptine 93s lism of serotonin in the brain. J Affect Dis 4, 275–290CrossRefGoogle Scholar
Weiss, CGorceix, AKindynis, SDimitriu, M (1981) Étude contrôlée à double insu versus nomifensine de l'activité et du délai d'action d'un nouvel antidépresseur la tianeptine (Perris, CStruwe, GJansson, B eds). Biological Psychiatry. Elsevier/North-Holland Biomedical Press, Amsterdam, New York, Oxford. Proceedings of the Third World Congress of Biological Psychiatry, Stockholm, June 28/July 3, 1981, 593–596Google Scholar
Willner, P (1985) Depression. A psychobiological synthesis. Wiley,New YorkGoogle Scholar
Willner, PMontgomery, T (1980) Neurotransmitters and depression: too much, too little, too unstable - or not unstable enough? Trends Neurosci 3, 201CrossRefGoogle Scholar
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