Skip to main content
SpringerLink
Log in

Tianeptine

A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Depression and Coexisting Anxiety and Depression

  • Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

An Erratum to this article was published on 01 July 1995

Abstract

Synopsis

Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile.

Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin (5-hydroxytryptamine; 5-HT) in rat brain synaptosomes and rat and human platelets, increases 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebral tissue and plasma, and reduces serotonergic-induced behaviour. Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, antagonises stress-induced behavioural deficits and prevents changes in cerebral morphology.

The antidepressant efficacy of tianeptine, as shown in 2 trials of patients with major depression or depressed bipolar disorder with or without melancholia, is greater than that of placebo. In patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, Imipramine and fluoxetine and may be superior to that of maprotiline in patients with coexisting depression and anxiety. However, submaximal dosages of amitriptyline and maprotiline were used in these studies. Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups.

Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, Imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used. Studies of tianeptine in patients with primary anxiety have not been conducted.

Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. The incidence o f dry mouth (38 vs 20%), constipation (19 vs 15%), dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%) and postural hypotension (8 vs 3%) are greater with amitriptyline than with tianeptine. Insomnia and nightmares occur in more tianeptine than amitriptyline recipients (20 vs 7%). The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increased sensitivity to the adverse effects associated with psychotropic drugs. Discontinuation of tianeptine has not been associated with a withdrawal syndrome, and no deaths from overdosage have been reported.

Thus, tianeptine is a unique antidepressant agent that increases the reuptake of serotonin while paradoxically having well documented therapeutic activity compared with other antidepressant agents. Tianeptine also has anxiolytic properties in patients with coexisting depression and anxiety, and appears to have a more favourable tolerability profile than amitriptyline in terms of anticholinergic, sedative and cardiovascular adverse effects. These properties may be particularly useful in patients with coexisting anxiety and depression, and in the elderly and patients withdrawing from the effects of alcohol.

Pharmacodynamic Properties

Tianeptine is a novel antidepressant agent that, in contrast with classical tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs), stimulates presynaptic serotonin (5-hydroxytryptamine; 5-HT) uptake in rat brain (cortex and hippocampus) and rat and human platelets following both short and long term administration. Tianeptine and its metabolites have no effect on serotonin uptake in vitro. The activity of tianeptine appears to be selective for serotonergic mechanisms although most reports show that the drug does not bind to serotonin receptor subtypes.

Tianeptine does not directly affect the uptake or release of dopamine or interfere with monoamine oxidase activity or monoamine uptake. However, the drug increases levels of the dopamine metabolite dihydroxyphenylacetic acid and increases extracellular concentrations of dopamine.

In contrast to other tricyclic antidepressants and paroxetine, tianeptine reduced most 5-hydroxytryptophan (5-HTP; a serotonin precursor)-induced behaviours in rats while the drug had no effect on behaviour elicited by postsynaptic serotonin receptor stimulation. However, after 4 weeks’ tianeptine administration, behavioural responses to tryptophan or 5-HTP were unaffected or intensified and were similar to those with paroxetine. The antidepressant properties of tianeptine have been demonstrated in animal models of depression. Tianeptine also reduced anxiety in the rat (social interaction test) and counteracted benzodiazepine and ethanol withdrawal-induced anxiety.

Tianeptine reduces stimulation of the hypothalamic-pituitary-adrenal axis in response to stress, antagonises stress-induced behavioural deficits in animal models of depression, and prevents stress- or corticosterone-induced changes in cerebral morphology. Although the exact mechanism of these effects is unknown, evidence suggests that the effects of tianeptine on serotonin reuptake account for these observations.

Tianeptine had no significant effects on memory or vigilance in healthy volunteers; single doses had activating effects followed by sedation according to electroencephalographic (EEG) mapping. Tianeptine does not significantly affect sleep EEG parameters in healthy volunteers.

Pharmacokinetic Properties

Maximum plasma concentration (Cmax) was 0.3 mg/L, time to Cmax (tmax) was 0.94h and bioavailability was 99% following a single oral dose of tianeptine 12.5mg in young healthy volunteers. The drug is not subject to first-pass hepatic metabolism. Food delays, but does not affect the extent of, absorption. The apparent volume of distribution of tianeptine is low (0.5 to 0.8 L/kg) and protein binding is high (95%). The pharmacokinetics of tianeptine are linearly related to dose.

Tianeptine is extensively metabolised by extrarenal routes; <3% of the dose is excreted unchanged in the urine. β-Oxidation is the major metabolic pathway. MC5 (pentanoic acid) and MC3 (propionic acid) are the major metabolites in plasma and urine, respectively; MC5 possesses antidepressant activity.

The overall pharmacokinetic profile of single doses of tianeptine in adults with depression is similar to that in healthy volunteers although the terminal elimination half-life (t½β) is longer (6.3 vs 2.5h). Furthermore, the overall pharmacokinetics of tianeptine at steady-state are similar to those after single dose administration although area under the concentration-time curve (AUC) was significantly higher after 1 month than after a single dose (1.3 vs 1 mg/L ∙ h).

The t½β and AUC of MC5 following a single oral dose of tianeptine 12.5mg were increased in patients with chronic renal failure. Similarly, t½β of tianeptine (after oral and intravenous administration) was increased, clearance of tianeptine (after intravenous administration) was decreased, and the Cmax and tmax of MC5 (after oral administration) were increased in the elderly compared with younger counterparts. Thus, dosage adjustments are recommended in patients with chronic renal failure and in the elderly. Dosage adjustments do not appear to be necessary in patients undergoing haemodialysis or those with chronic alcoholism, and are not likely to be necessary in patients with compensated hepatic impairment.

Therapeutic Efficacy

The efficacy of tianeptine in the treatment of depression was greater than that of placebo in 2 trials of patients with major depression or depressed bipolar disorder, with or without melancholia. Furthermore, the antidepressant efficacy of tianeptine 25 to 50 mg/day administered for 4 weeks to 3 months appeared to be similar to that of amitriptyline 50 to 100 mg/day, imipramine 100 to 200 mg/day and fluoxetine 20 mg/day in patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymia. However, it must be noted that submaximal dosages of amitriptyline were used in these studies. Response rates of 58 to 78%, according to Montgomery-Åsberg Depression Rating Scale (MÅDRS), Hamilton Depression Rating Scale (HDRS) or Clinical Global Impression (CGI) scores, have been reported with tianeptine. Evidence from a noncomparative trial suggests that tianeptine may also be effective in patients with endogenous depression.

Therapeutic benefits observed after short term therapy appear to progressively improve with long term (up to 1 year) tianeptine therapy. Furthermore, prolonged tianeptine treatment may also reduce the incidence of relapse and recurrence of depression. A placebo-controlled trial of long term therapy with this drug is currently under way.

The anxiolytic properties of tianeptine appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline in patients with depression and coexisting anxiety; however, submaximal dosages of amitriptyline and maprotiline were used and studies of tianeptine in patients with primary anxiety have not been conducted. Tianeptine reduced Hamilton Anxiety Rating Scale (HARS) scores by 36 to 66%. Furthermore, tianeptine appeared to reduce the need for concomitant anxiolytics compared with fluoxetine.

Short term tianeptine therapy effectively reduced depression and anxiety in elderly patients with major depression without melancholia or psychotic features or dysthymic disorder. Therapeutic benefits were at least sustained in the long term. Tianeptine was also effective in the treatment of patients with major depression or dysthymic disorder following alcohol withdrawal.

Tolerability

Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. In a general practice study involving 1858 patients with depression treated with tianeptine for 3 months, the most common adverse events were dry mouth (12%), constipation (4%), bitter taste (4%), ‘change in dreaming’ (4%), drowsiness (4%), weight gain (3%), agitation/tension (3%) and nausea (3%). In more than 3300 patients treated with tianeptine for up to 1 year, no significant changes in heart rate, blood pressure, cardiac conduction or ventricular function were observed. Less than 5% of patients withdrew from short or long term tianeptine treatment because of an adverse event.

Tianeptine appears to have a lower propensity to cause sedative, anticholinergic and cardiovascular effects than classical tricyclic antidepressant agents. In a review of double-blind trials, dry mouth (38 vs 20%) occurred in significantly more amitriptyline than tianeptine recipients; heart rate increased with amitrip-tyline and decreased with tianeptine. There was also a trend towards more dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%), postural hypotension (8 vs 3%) and constipation (19 vs 15%) with amitriptyline. Insomnia and nightmares occurred in significantly more tianeptine than amitriptyline recipients (20 vs 7%). No significant electrocardiographic (ECG) changes were observed with tianeptine. The tolerability profile of tianeptine was similar to that of fluoxetine in a clinical trial.

The low incidences of anticholinergic effects, sedation and cardiotoxicity make tianeptine particularly attractive for use in the elderly and in patients with previous alcoholism who are known to have increased sensitivity to the adverse effects of psychotropic agents. A review of noncomparative trials involving 549 elderly patients, and a long term trial of tianeptine in 130 patients with depression following alcohol withdrawal support the favourable tolerability profile of tianeptine in these patient groups.

Dosage and Administration

Tianeptine 12.5mg 3 times daily is the recommended dosage in patients with depression. Some patients may benefit from a dosage of 50 mg/day whereas a reduced daily dosage of 25 mg/day is recommended in patients with severe renal failure and in the elderly. Progressive therapeutic improvements have been observed over a 1-year period and long term treatment may reduce depressive relapse or recurrence.

Salicylic acid decreases the protein binding of tianeptine. Therefore, a reduced dosage of tianeptine is recommended when high dosages of salicylic acid are concomitantly administered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Labrid C, Mocaër E, Kamoun A. Neurochemical and pharmacological properties of tianeptine, a novel antidepressant. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 56–60

    Google Scholar 

  2. Ansseau M. The paradox of tianeptine. Eur Psychiatry 1993; 8 Suppl. 2: 89s–93s

    Google Scholar 

  3. Curzon G. Serotonergic mechanisms of depression. Clin Neuropharmacol 1988; 11 Suppl. 2: 11–20

    Google Scholar 

  4. Mennini T, Mocaer E, Garattini S. Tianeptine, a selective enhancer of serotonin uptake in rat brain. Naunyn Schmiedebergs Arch Pharmacol 1987 Nov; 336: 478–82

    PubMed  CAS  Google Scholar 

  5. Koshikawa N, Mocaër E, Stephenson JD. The effects of tianeptine on wet-dog shakes, fore-paw treading and a flexor reflex in rats are consistent with enhancement of 5-hydroxytrypt-amine uptake. Eur J Pharmacol 1991 May 30; 198: 51–7

    PubMed  CAS  Google Scholar 

  6. Ortiz J, Mocaër E, Artigas F. Effects of the antidepressant drug tianeptine on plasma and platelet serotonin concentrations in the rat. Eur J Pharmacol 1991 Jul 9; 199: 335–9

    PubMed  CAS  Google Scholar 

  7. Fattaccini CM, Bolaños Jimenez F, Gozlan H, et al. Tianeptine stimulates uptake of 5-hydroxytryptamine in vivo in the rat brain. Neuropharmacology 1990 Jan; 29: 1–8

    PubMed  CAS  Google Scholar 

  8. Invernizzi R, Pozzi L, Garattini S, et al. Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism. Neuropharmacology 1992 Mar; 31: 221–7

    PubMed  CAS  Google Scholar 

  9. Sacchetti G, Bonini I, Waeterloos GC, et al. Tianeptine raises dopamine and blocks stress-induced noradrenaline release in the rat frontal cortex. Eur J Pharmacol 1993 May 19; 236: 171–5

    PubMed  CAS  Google Scholar 

  10. Bertorelli R, Amoroso D, Girotti P, et al. Effect of tianeptine on the central cholinergic system: involvement of serotonin. Naunyn Schmiedebergs Arch Pharmacol 1992 Mar; 345: 276–81

    PubMed  CAS  Google Scholar 

  11. Garattini S. Tianeptine enhances 5-HT uptake and inhibits experimental depression and stress [abstract 1402]. 9th World Congress of Psychiatry; 1993 Jun 6–12

  12. Kato G, Weitsch AF. Neurochemical profile of tianeptine, a new antidepressant drug. Clin Neuropharmacol 1988; 11 Suppl 2: S43–50

    PubMed  CAS  Google Scholar 

  13. Mocaër E, Rettori MC, Kamoun A. Pharmacological antidepressive effects and tianeptine-induced 5-HT uptake increase. Clin Neuropharmacol 1988; 11 Suppl 2: S32–42

    PubMed  Google Scholar 

  14. Datla KP, Curzon G. Behavioural and neurochemical evidence for the decrease of brain extracellular 5-HT by the antidepressant drug tianeptine. Neuropharmacology 1993 Sep; 32: 839–45

    PubMed  CAS  Google Scholar 

  15. Whitton PS, Sarna GS, O’Connell MT, et al. The effect of the novel antidepressant tianeptine on the concentration of 5-hydroxytryptamine in rat hippocampal dialysates in vivo. Neuropharmacology 1991 Jan; 30: 1–4

    PubMed  CAS  Google Scholar 

  16. Coppen AJ, Doogan BP. Serotonin and its place in the pathogenesis of depression. J Clin Psychiatry 1988; 49 Suppl: 4–11

    Google Scholar 

  17. Chamba G, Lemoine P, Flachaire E, et al. Increased serotonin platelet uptake after tianeptine administration in depressed patients. Biol Psychiatry 1991 Sep 15; 30: 609–17

    PubMed  CAS  Google Scholar 

  18. Ortiz J, Mariscot C, Alvarez E, et al. Effects of the antidepressant drug tianeptine on plasma and platelet serotonin of depressive patients and healthy controls. J Affect Disord 1993 Dec; 29: 227–34

    PubMed  CAS  Google Scholar 

  19. De Simoni MG, Deluigi A, Clavenna A, et al. In vivo studies on the enhancement of serotonin reuptake by tianeptine. Brain Res 1992 Mar 6; 574: 93–7

    PubMed  Google Scholar 

  20. Whitton PS, Sarna GS, Datla KP, et al. Effects of tianeptine on stress-induced behavioural deficits and 5-HT dependent behaviour. Psychopharmacology 1991; 104(1): 81–5

    PubMed  CAS  Google Scholar 

  21. Stephenson JD, Koshikawa N, Rettori M-C. Comparison of the effects of acute and chronic tianeptine on 5-HT-evoked behaviours of rats [abstract 487]. 9th World Congress of Psychiatry; 1993 Jun 6–12

  22. Koshikawa N, Tomiyama K, Stephenson JD. Effects of acute and chronic treatments with tianeptine and paroxetine on 5-HTP-evoked changes in 5-HT content of rat hippocampal dialysates [abstract]. Br J Pharmacol 1994; 112: 309

    Google Scholar 

  23. Chaouloff F. Effects of tianeptine on 5-HTP-induced and dextrofenfluramine-induced hypophagia in the rat. Pharmacol Biochem Behav 1993 Apr; 44: 989–92

    PubMed  CAS  Google Scholar 

  24. Romero G, Toscano E, Montero D, et al. Effect of prenatal exposure to tianeptine on different neurotransmitter receptors and 5-HT-stimulated inositol phosphate formation in rat brain. J Neural Transm Gen Sect 1992; 90: 113–24

    PubMed  CAS  Google Scholar 

  25. Watanabe Y, Sakai RR, McEwen BS, et al. Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin. Brain Res 1993 Jun 25; 615: 87–94

    PubMed  CAS  Google Scholar 

  26. Mennini T, Garattini S. Neurobiology of tianeptine. Anew pharmaceutic agent [in French]. Presse Med 1991 Nov 14; 20: 1823–7

    PubMed  CAS  Google Scholar 

  27. Murdoch D, McTavish D. Sertraline: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs 1992; 44(4): 604–24

    PubMed  CAS  Google Scholar 

  28. Kuroda Y, Watanabe Y, McEwen BS. Tianeptine decreases both serotonin transporter mRNA and binding sites in rat brain. Eur J Pharmacol 1994; 268: R3–5

    PubMed  CAS  Google Scholar 

  29. Tanda G, Carboni E, Frau R, et al. Increase of extracellular dopamine in the prefrontal cortex: a trait of drugs with antidepressant potential? Psychopharmacology 1994; 115: 285–8

    PubMed  CAS  Google Scholar 

  30. Dresse A, Scuvée-Moreau J. Electrophysiological effects of tianeptine on rat locus coeruleus, raphe dorsalis, and hippocampus activity. Clin Neuropharmacol 1988; 11 Suppl 2: S51–8

    PubMed  CAS  Google Scholar 

  31. Dresse A, Scuvée-Moreau J, Mocaër E, et al. Electrophysiologic studies of tianeptine and other antidepressants [in French]. Presse Med 1991 Nov 14; 20: 1807–11

    PubMed  CAS  Google Scholar 

  32. Blier P, Piñeyro G, Deveault L, et al. Electrophysiological effects of acute and long-term tianeptine administration on serotonin neurotransmission [abstract]. Eur Psychiatry 1994; 9 Suppl. 1: 141s

    Google Scholar 

  33. Kelly JP, Leonard BE, Rettori M-C. The effects of tianeptine and sertraline in 3 animal models of depression [abstract 783]. 9th World Congress of Psychiatry; 1993 Jun 6–12

  34. File SE, Mabbutt PS. Effects of tianeptine in animal models of anxiety and on learning and memory. Drug Dev Res 1991; 23(1):47–56

    CAS  Google Scholar 

  35. File SE, Andrews N, Zangrossi Jr H. Tianeptine counteracts the anxiogenic effects of benzodiazepine withdrawal, but not those of exposure to cat odour. Eur Psychiatry 1993; 8 Suppl. 2: 75–80

    Google Scholar 

  36. File SE, Andrews N, al-Farhan M. Anxiogenic responses of rats on withdrawal from chronic ethanol treatment: effects of tianeptine. Alcohol Alcohol 1993 May; 28: 281–6

    PubMed  CAS  Google Scholar 

  37. Checkley S. Neuroendocrine mechanisms and the precipitation of depression by life events. Br J Psychiatry 1992; 160 Suppl. 15: 7–17

    Google Scholar 

  38. Delbende C, Delarue C, Lefebvre H, et al. Glucocorticoids, transmitters and stress. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 24–34

    Google Scholar 

  39. Delbende C, Mocaër E, Rettori M, et al. Effect of the antidepressant tianeptine on the activity of the hypothalamo-pitu-itary-adrenal axis. Eur Psychiatry 1993; 8 Suppl. 2: 49s–54s

    Google Scholar 

  40. Broqua P, Baudrie V, Laude D, et al. Influence of the novel antidepressant tianeptine on neurochemical, neuroendocrinological, and behavioral effects of stress in rats. Biol Psychiatry 1992 Feb 15; 31: 391–400

    PubMed  CAS  Google Scholar 

  41. Guillaume V, Magnan E, Cataldi M, et al. Effect of tianeptine on the hypothalamic control of the corticotrophic response to stress. Eur Psychiatry 1993; 8 Suppl. 2: 55s–60s

    Google Scholar 

  42. Fontanges R, Mimouni J, de Grieve X, et al. Effect of tianeptine on neuroendocrine, enzyme and behavioral responses to restraint stress in male rats. Eur Psychiatry 1993; 8 Suppl. 2: 67–73

    Google Scholar 

  43. Curzon G, Datla KP. Effects of tianeptine on behavioural and neurochemical responses to immobilization stress. Eur Psychiatry 1993; 8 Suppl. 2: 61s–6s

    Google Scholar 

  44. Curzon G, Kennett GA, Sarna GS, et al. The effects of tianeptine and other antidepressants on a rat model of depression. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 51–5

    Google Scholar 

  45. Bueno L, Fioramonti J, Rettori MC. Inhibition of stress-induced colonic motor alterations by tianeptine [abstract 782]. 9th World Congress of Psychiatry; 1993 Jun 6–12

  46. Delbende C, Contesse V, Mocaër E. The novel antidepressant, tianeptine, reduces stress-evoked stimulation of the hypothalamo-pituitary-adrenal axis. Eur J Pharmacol 1991 Sep 24; 202: 391–6

    PubMed  CAS  Google Scholar 

  47. Delbende C, Tranchand Bunel D, Tarozzo G, et al. Effect of chronic treatment with the antidepressant tianeptine on the hypothalamo-pituitary-adrenal axis. Eur J Pharmacol 1994 Jan 14; 251: 245–51

    PubMed  CAS  Google Scholar 

  48. McEwen BS. Stress and the hippocampus. An update on current knowledge [in French]. Presse Med 1991 Nov 14; 20: 1801–6

    PubMed  CAS  Google Scholar 

  49. McEwen BS, Gould EA, Sakai RR. The vulnerability of the hippocampus to protective and destructive effects of glucocorticoids in relation to stress. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 18–23

    Google Scholar 

  50. Mennini T, Taddei C, Codegoni A, et al. Acute noise stress reduces [3H]5-hydroxytryptamine uptake in rat brain synap-tosomes: protective effects of buspirone and tianeptine. Eur J Pharmacol 1993 Sep 14; 241: 255–60

    PubMed  CAS  Google Scholar 

  51. Watanabe Y, Gould E, Daniels DC, et al. Tianeptine attenuates stress-induced morphological changes in the hippocampus. Eur J Pharmacol 1992 Nov 3; 222: 157–62

    PubMed  CAS  Google Scholar 

  52. Broqua P, Baudrie V, Chaouloff F. Differential effects of the novel antidepressant tianeptine on L-5-hydroxytryptophan (5-HTP)-elicited corticosterone release and body weight loss. Eur Neuropsychopharmacol 1992 Jun; 2: 115–20

    PubMed  CAS  Google Scholar 

  53. McEwen BS, Angulo J, Gould E, et al. Antidepressant modulation of isolation and restraint stress effects on brain chemistry and morphology. Eur Psychiatry 1993; 8 Suppl. 2: 41–8

    Google Scholar 

  54. Poirier MF, Galinowski A, Amado-Boccara I, et al. Effects of tianeptine on attention, memory and psychomotor performance using neuropsychological methods in young healthy volunteers. Eur Psychiatry 1993; 8 Suppl. 2: 95s–102s

    Google Scholar 

  55. von Frenckell R, Ansseau M, Dulcire C, et al. Effects of tianeptine on vigilance and memory in young healthy volunteers. Psychiatr & Psychobio 1990; 5: 375–80

    Google Scholar 

  56. Saletu B, Grimberger J, Anderer P, et al. Comparative pharmacodynamic studies with the novel serotonin uptake-enhancing tianeptine and inhibiting fluvoxamine utilizing EEG mapping and psychometry. J Neural Transm (Submitted)

  57. Staner L, Bertolino A, Cassano GB, et al. European multicentre study of tianeptine versus imipramine and placebo in the treatment of major depression and depressed bipolar disorder [abstract]. Eur Psychiatry 1994; 9 Suppl. 1: 140s

    Google Scholar 

  58. Mendlewicz J. Sleep EEG study of acute administration of tianeptine in ten young healthy volunteers. A double-blind placebo-controlled study. Servier. C-1574-214-BEL, volume 1/6; 1994 (Data on file)

  59. Daoust M, Compagnon P, Legrand E, et al. Tianeptine, a specific serotonin uptake enhancer, decreases ethanol intake in rats — rapid communication. Alcohol Alcohol 1992 Jan; 27: 15–7

    PubMed  CAS  Google Scholar 

  60. Jaffard R, Mocaer E, Poignant J-C, et al. Effects of tianeptine on spontaneous alternation, simple and concurrent spatial discrimination learning and on alcohol-induced alternation deficits in mice. Behav Pharmacol 1991 Feb; 2: 37–46

    PubMed  Google Scholar 

  61. Nicot G, Lachatre G, Gonnet C, et al. Ion-pair extraction and high-performance liquid chromatographic determination of tianeptine and its metabolites in human plasma, urine and tissues. J Chromatogr 1986 Aug 22; 381: 115–26

    PubMed  CAS  Google Scholar 

  62. Salvadori C, Ward C, Defrance R, et al. The pharmacokinetics of the antidepressant tianeptine and its main metabolite in healthy humans — influence of alcohol co-administration. Fundam Clin Pharmacol 1990; 4: 115–25

    PubMed  CAS  Google Scholar 

  63. Grislain L, Gele P, Bertrand M, et al. The metabolic pathways of tianeptine, a new antidepressant, in healthy volunteers. Drug Metab Dispos 1990 Oct; 18: 804–8

    PubMed  CAS  Google Scholar 

  64. Royer RJ, Albin H, Barrucand D, et al. Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors. Clin Neuropharmacol 1988; 11 Suppl 2:S90–6

    PubMed  CAS  Google Scholar 

  65. Bouyer I, Farinotti R, Gelé P, et al. Metabolism of tianeptine after single and multiple dosing in man [abstract 31.02.35]. Psychopharmacology 1988; 96 Suppl.: 275

    Google Scholar 

  66. Dresse A, Rosen JM, Brems H, et al. Influence of food on tianeptine and its main metabolite kinetics. J Clin Pharmacol 1988 Dec; 28: 1115–9

    PubMed  CAS  Google Scholar 

  67. Ansseau M, Wauthy J, von Frenckell R, et al. Gradually increased doses of tianeptine: maximal tolerated dose and linearity of the pharmacokinetics [abstract]. An Psiquiatria 1992; 8 Suppl. 1: 56

    Google Scholar 

  68. Ansseau M. Tolerance and pharmacokinetic study following single oral increasing doses of tianeptine sodium salt in healthy male volunteers. Servier. P2.R.92.10.01574.HPK; Jan, 1993 (Data on file)

  69. Riché C. The pharmacokinetics of tianeptine and its MC5 metabolite on repeated dosing in depressed adults. Servier. PMH 1574 01 021; Aug, 1991 (Data on file)

  70. Salvadori C, Merdjan H, Brouard R, et al. Tianeptine and its main metabolite. Disposition in chronic renal failure and haemodialysis. Fundam Clin Pharmacol 1990; 4: 663–71

    PubMed  CAS  Google Scholar 

  71. Zini R, Morin D, Salvadori C, et al. Tianeptine binding to human plasma proteins and plasma from patients with hepatic cirrhosis or renal failure. Br J Clin Pharmacol 1990 Jan; 29: 9–18

    PubMed  CAS  Google Scholar 

  72. Royer RJ, Royer-Morrot MJ, Paille F, et al. Tianeptine and its main metabolite pharmacokinetics in chronic alcoholism and cirrhosis. Clin Pharmacokinet 1989 Mar; 16: 186–91

    PubMed  CAS  Google Scholar 

  73. Grasela TH, Fiedler-Kelly JB, Salvadori C, et al. Development of a population pharmacokinetic database for tianeptine. Eur J Clin Pharmacol 1993; 45(2): 173–9

    PubMed  CAS  Google Scholar 

  74. Grasela TH, Fiedler-Kelly JB, Salvadori C, et al. Predictive performance of pre-marketing tianeptine pharmacokinetic parameters as applied to post-marketing data [abstract]. Clin Pharmacol Ther 1993 Feb; 53: 215

    Google Scholar 

  75. Carlhant D, Le Garrec J, Guedes Y, et al. Pharmacokinetics and bioavailability of tianeptine in the elderly. Drug Invest 1990; 2(3): 167–72

    Google Scholar 

  76. Demotes-Mainard F, Galley P, Manciet G, et al. Pharmacokinetics of the antidepressant tianeptine at steady state in the elderly. J Clin Pharmacol 1991 Feb; 31: 174–8

    PubMed  CAS  Google Scholar 

  77. Jeanniot JP. A study of the pharmacokinetics of tianeptine and its metabolite MC5 in the elderly depressed patient after single and repeated administration of tianeptine sodium salt. Servier. P2.R.90.22.01574.HPK; Jun, 1991 (Data on file)

  78. Bourgeois M, Delalleau B, Féline A, et al. Tianeptine in episodes of major depression with melancholia and signs of endogenicity [in French]. Presse Med 1991 Nov 14; 20: 1837–43

    PubMed  CAS  Google Scholar 

  79. Guelfi JD, Dulcire C, Le-Moine P, et al. Clinical safety and efficacy of tianeptine in 1,858 depressed patients treated in general practice. Neuropsychobiology 1992; 25: 140–8

    PubMed  CAS  Google Scholar 

  80. Costae Silva JA, Ruschel SS. Tianeptine versus placebo study in major depressions and depressive bipolar disorders [abstract]. Eur Psychiatry 1994; 9 Suppl. 1: 140

    Google Scholar 

  81. Costa e Silva JA. Efficacy of tianeptine in the treatment of major depressive episodes with or without melancholia. A double-blind study: tianeptine versus placebo. Servier. CN-1574-207-BRA; Oct, 1994 (Data on file)

  82. Bersani G, Pasini A, Brancato T, et al. Serotonin and depression: controlled multicentred study — tianeptine vs amitriptyline [in Italian]. Stand Diagn Epidemiol 1989: 1243-9

  83. Guelfi JD, Pichot P, Dreyfus JF. Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptyline. Neuropsychobiology 1989; 22: 41–8

    PubMed  CAS  Google Scholar 

  84. Invernizzi G, Aguglia E, Bertolino A, et al. The efficacy and safety of tianeptine in the treatment of depressive disorder: results of a controlled double-blind multicentre study vs. amitriptyline. Neuropsychobiology 1994; 30: 85–93

    PubMed  CAS  Google Scholar 

  85. Cassano GB, Lôo H, Mendlewicz J. Efficacy of tianeptine in the treatment of major depressions (single episode or recurrent) and depressed bipolar disorders. A double-blind study: tianeptine versus placebo and imipramine. Servier. CI-1574-205; Oct, 1994 (Data on file)

  86. Alby JM, Ferreri M, Cabanne J, et al. Efficacy of tianeptine (Stablon™) for the treatment of major depression and dysthymia with somatic complaints. A comparative study versus fluoxetine (Prozac™) [in French]. Ann de Psychiatrie 1993; 8(2): 136–44

    Google Scholar 

  87. Chaby L, Grinsztein A, Weitzman JJ, et al. Anxio-depressive disorders in menopausal and pre-menopausal women. Double blind study of tianeptine versus maprotiline [in French]. Presse Med 1993 Jul 3–10; 22: 1133–8

    PubMed  CAS  Google Scholar 

  88. Guelfi JD, Dulcire C, Le Moine P, et al. Extensive study of tianeptine in general practice. Preliminary results. Drug Invest 1990; 2(4): 268–72

    Google Scholar 

  89. Guelfi JD. Efficacy of tianeptine in comparative trials versus reference antidepressants. An overview. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 72–5

    Google Scholar 

  90. Lôo H, Ganry H, Dufour H, et al. Long-term use of tianeptine in 380 depressed patients. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 61–5

    Google Scholar 

  91. Sarteschi P, Bersani G, Ciani N, et al. Long-term treatment of depression by tianeptine [abstract]. Eur Neuropsycho-pharmacol 1993 Sep; 3 Spec, issue: 333–4

    Google Scholar 

  92. Raffaitin F. Efficacy and acceptability of tianeptine in the elderly: a review of clinical trials. Eur Psychiatry 1993; 8 Suppl. 2: 117s–24s

    Google Scholar 

  93. Malauzat D, Danic C, Peyrouzet J-M, et al. Interest and necessity of long term antidepressant treatment in elderly patients, after resolution of depressive episode [in French]. Psychol Med 1990; 22(9): 903–22

    Google Scholar 

  94. Chapuy P, Cuny G, Delomier Y, et al. Tianeptine and depression in 140 elderly patients treated for 1 year [in French]. Presse Med 1991 Nov 14; 20: 1844–52

    PubMed  CAS  Google Scholar 

  95. Malka R, Lôo H, Ganry H, et al. Long-term administration of tianeptine in depressed patients after alcohol withdrawal. Br J Psychiatry 1992 Feb; 160 Suppl. 15: 66–71

    Google Scholar 

  96. Björk K. The efficacy of zimeldine in preventing depressive episodes in recurrent major depressive disorders — a double-blind placebo-controlled study. Acta Psychiatr Scand 1983; 68 Suppl. 308: 182–9

    Google Scholar 

  97. Lôo H, Ganry G, Dufour H, et al. Role of tianeptine in preventing depression relapse and recurrence. Early estimation [in French]. Presse Med 1991 Nov 14; 20: 1864–8

    PubMed  Google Scholar 

  98. Mindham RHS, Howland C, Shepherd M. An evaluation of continuation therapy with tricyclic antidepressants in depressive illness. Psychol Med 1973; 3: 5–17

    PubMed  CAS  Google Scholar 

  99. Stein MK, Rickels K, Weise C. Maintenance therapy with amitriptyline: a controlled trial. Am J Psychiatry 1980; 137: 370–1

    PubMed  CAS  Google Scholar 

  100. Montgomery SA, Dufour H, Brion S, et al. The prophylactic efficacy of fluoxetine in unipolar depression. Br J Psychiatry 1988; 153 Suppl. 3: 69–75

    Google Scholar 

  101. Kupfer DJ, Frank E, Perel JM, et al. Five-year outcome for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1992; 49: 769–73

    PubMed  CAS  Google Scholar 

  102. Malka R. Role of drug therapies in the treatment of alcoholism: alcohol and anxiety — alcohol and depression. Clin Neuropharmacol 1988; 11 Suppl. 2: S69–73

    PubMed  Google Scholar 

  103. Lôo H, Malka R, Defiance R, et al. Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients. Neuropsychobiology 1988; 19: 79–85

    PubMed  Google Scholar 

  104. Macher JP, Minot R, Duval F, et al. Neuroelectrophysiologic studies in alcoholic patients, undergoing withdrawal and depressed, and treated by tianeptine [in French]. Presse Med 1991 Nov 14; 20: 1853–7

    PubMed  CAS  Google Scholar 

  105. Favre JD, Lôo H, Marey C, et al. Long-term efficacy of tianeptine on alcoholic relapses in non-depressed alcoholic patients. Preliminary results. Eur Psychiatry 1993; 8 Suppl. 2: 125–9

    Google Scholar 

  106. Delalleau B, Dulcire C, Le-Moine P, et al. Analysis of the side effects of tianeptine. Clin Neuropharmacol 1988; 11 Suppl. 2: S83–9

    PubMed  Google Scholar 

  107. Juvent M, Douchamps J, Delcourt E, et al. Lack of cardiovascular side effects of the new tricyclic antidepressant tianeptine. A double-blind, placebo-controlled study in young healthy volunteers. Clin Neuropharmacol 1990 Jan—Feb; 13: 48–57

    PubMed  CAS  Google Scholar 

  108. Lôo H, Delalleau N, Kamoun A. Tianeptine: clinical properties. Eur Psychiatry 1993; 8 Suppl. 2: 103s–9s

    Google Scholar 

  109. Lasnier C, Marey C, Lapeyre G. Cardiovascular tolerance to tianeptine [in French]. Presse Med 1991 Nov 14; 20: 1858–63

    PubMed  CAS  Google Scholar 

  110. Zini R, Morin D, Salvadori C, et al. The influence of various drugs on the binding of tianeptine to human plasma proteins. Int J Clin Pharmacol Ther Toxicol 1991 Feb; 29: 64–6

    PubMed  CAS  Google Scholar 

  111. Toon S, Holt BL, Langley SJ, et al. Pharmacokinetic and pharmacodynamic interaction between the antidepressant tianeptine and oxazepam at steady-state. Psychopharmacology 1990; 101: 226–32

    PubMed  CAS  Google Scholar 

  112. Larrey D, Tinel M, Lettéron P, et al. Metabolic activation of the new tricyclic antidepressant tianeptine by human liver cytochrome P450. Biochem Pharmacol 1990 Aug 1; 40: 545–50

    PubMed  CAS  Google Scholar 

  113. Angst J. Epidemiology of depression. Psychopharmacology 1992; 106 Suppl.: S71–74

    Google Scholar 

  114. Scott J. Epidemiology, demography and definitions. Int Clin Psychopharmacol 1991; 6 Suppl. 1: 1–12

    PubMed  Google Scholar 

  115. Smith HA, Wedlund PJ. Depression: its classification, epidemiology, expression and treatment. J Pharmacoepidemiol 1991; 2: 3–30

    Google Scholar 

  116. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the united states. Arch Gen Psychiatry 1994; 51: 8–19

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centonan Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Michelle I. Wilde & Paul Benfield

Authors
  1. Michelle I. Wilde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Benfield
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Various sections of the manuscript reviewed by: M. Ansseau, Centre Hospitalier Universitaire de Liège, Service de Psychiatrie, Domaine Universitaire du Sart Tilman, Liège, Belgium; A. Galinowski, Service Hospitalo-Universitaire de Santé Mentale et de Thérapeutique, Hôpital Sainte-Anne, Paris, France; J.D. Guelfi, Clinique des Maladies Mentales et de l’Encéphale, Paris, France; R.T. Joffe, Faculty of Health Sciences, Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada; S. Kasper, Psychiatric Department, University of Vienna, Vienna, Austria; N. Koshikawa, Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan; M. Lader, Clinical Psychopharmacology, Institute of Psychiatry, London, England; H. Lôo, Service Hospitalo-Universitaire de Santé Mentale et de Thérapeutique, Hôpital Sainte-Anne, Paris, France; B.S. McEwen, Laboratory of Neuroendocrinology, Rockefeller University, New York, New York, USA; T. Mennini, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy; E.H. Pi, Department of Psychiatry and the Behavioural Sciences, University of Southern California School of Medicine, Los Angeles, California, USA; R.M. Post, National Institute of Mental Health, Bethesda, Maryland, USA; J. Del Río, Departmento de Farmacologia, Universidad de Navarra, Pamplona, Spain; N. Sherwood, Human Psychopharmacology Research Unit, University of Surrey, Surrey, England; J.D. Stephenson, Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, London, England; P.S. Whitton, Department of Pharmacology, School of Pharmacy, University of London, London, England

An erratum to this article is available at http://dx.doi.org/10.1007/BF03260138.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilde, M.I., Benfield, P. Tianeptine. Drugs 49, 411–439 (1995). https://doi.org/10.2165/00003495-199549030-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199549030-00007

Keywords

Search

Navigation