Tianeptine: Wikis

  
  

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Tianeptine
Systematic (IUPAC) name
7-(3-Chloro-6-methyl-6,11-dihydrodibenzo[ c,f][1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide
Identifiers
CAS number 66981-73-5
ATC code N06AX14
PubChem 68870
Chemical data
Formula C 21H25ClN2O4S 
Mol. mass 436.953 g/mol
Pharmacokinetic data
Bioavailability 99 ± 29%[1]
Metabolism hepatic
Half life 2.5 hours (2.5 ± 1.1 h)[1]
Excretion Renal[1]
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes Oral

Tianeptine (INN) (Stablon, Coaxil, Tatinol) is a selective serotonin reuptake enhancer (SSRE) drug used for treating Major depressive episodes (mild, moderate, or severe). Unlike conventional tricyclic antidepressants, tianeptine enhances the reuptake of serotonin instead of inhibiting it, opposite to the action of SSRIs. Moreover, it enhances the extracellular concentration of dopamine in the nucleus accumbens.[2]

Tianeptine, indicated as a thymoleptic, reduces the effects of serotonin in the limbic system and the pre-frontal cortex, giving rise to a mood elevation, unlike the mood blunting associated with SSRIs. Like SSRIs, however, tianeptine's onset-of-action delay is approximately 2-6 weeks with improvements sometimes noticeable in as soon as one week.

Its short-lived, but pleasant, stimulant effect experienced by some patients is shared with its predecessor, amineptine, whose side effects related to dopamine uptake inhibitor activity resulted in Servier's research into Tianeptine. Suggested dosage is three times daily, due to its short duration of action. Tianeptine is synergistic and has been used in conjunction with other drugs such as modafinil.[3][4]

Tianeptine has a strong antidepressant and anxiolytic properties with a relative lack of sedative, anticholinergic and cardiovascular adverse effects, thus suggesting it is particularly suitable for use in elderly patients and in those following alcohol withdrawal; such patients can be more sensitive to the adverse effects of psychotropic drugs.[5]

Currently, tianeptine is approved in France and manufactured and marketed by Laboratoires Servier SA; it is also marketed in a number of other European countries under the trade name Coaxil as well as in Asia and Latin America as Tatinol.

Contents

Uses

Approved

Tianeptine shows efficacy against serious depressive episodes (major depression), comparable to amitriptyline, imipramine and fluoxetine, but with fewer side effects. It was shown to be more effective than maprotiline in a group of patients with co-existing depression and anxiety. Tianeptine also displays significant anxiolytic properties and is useful in treating a spectrum of anxiety disorders including panic disorder, as evidenced by a study in which those administered 35% CO2 gas (carbogen) on paroxetine (Paxil) or tianeptine (Stablon) therapy showed equivalent panic-blocking effects.[6]

Investigational and ongoing research

Tianeptine has been reported to be very effective for asthma starting in August 1998, when Dr. Fuad Lechin and colleagues at the Central University of Venezuela Institute of Experimental Medicine in Caracas published the results of a 52-week randomized controlled trial of asthmatic children; the children in the groups that received tianeptine had a sharp decrease in clinical rating and increased lung function.[7] Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic patients.[8] As tianeptine was the only agent known to both reduce free serotonin in plasma and enhance uptake in platelets, they decided to use it to see if reducing free serotonin levels in plasma would help.[7] By November 2004, there had been two double-blind placebo-controlled crossover trials, and a 25,000+ patient open-label study lasting over seven years, all showing effectiveness.[9] A 2005 study in Egypt demonstrated tianeptine to be effective in men with depression and erectile dysfunction.[10] Tianeptine also has anticonvulsant and analgesic effects,[11] and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to fibromyalgia.[12] Tianeptine is also being studied in the treatment of ADD/ADHD.

It is currently being researched for its effectiveness in irritable bowel syndrome.[13]

Tinaneptine has been found to be effective in depression in Parkinson's disease.[14] and in chronic posttraumatic stress disorder [15] of which is was as effective and safe as fluoxetine (an SSRI)and moclobemide (an MAO-A inhibitor)[16]

Contraindications

According to Servier International, tianeptine is contraindicated in children under 15 years of age, people taking MAOIs, and pregnant or lactating women.[17] However, as of 2005, there are no studies published showing increased risk of birth defects.[18]

Side effects

Tianeptine was both studied for short-term (3 month) and long-term treatment (12 months) and equally well tolerated. The studies encompassed 1,300 to nearly 3,000 patients each.

Side effects are as follows (Amitriptyline vs Tianeptine):

  • dry mouth (38% vs 20%)
  • constipation (19% vs 15%)
  • dizziness/syncope (23% vs 13%)
  • drowsiness (17% vs 10%)
  • postural hypotension (8% vs 3%)
  • Insomnia and vivid dreams (7% vs 20%)

Costa e Silva and colleagues at the Jardim Botanico in Rio de Janeiro, Brazil reported a greater frequency of headaches in the tianeptine group as compared with placebo.[19]

Sema Gülen Yıldırım and colleagues reported in 2004 of a case of hypomania caused by tianeptine.[20]

Interestingly, tianeptine along with its two metabolites (S8849, S3139) does not affect the reuptake of monoamines (DA, 5-HT, and noradrenaline) in vitro. Results from in vivo studies confirm that serotonin reuptake is enhanced -while dopamine and noradrenaline are unaffected- suggesting a mechanism independent of SERT.[21] No data is available regarding effects of the drug on postsynaptic receptors.

Drug interactions

No sufficient data available at present date.

Usual doses

Although Servier's official recommendation is 12.5 mg three times per day before the main meals of the day, lower or higher doses may be used as determined by your prescribing physician.

Coping with suicide risks

As is generally true for activating/nonsedating antidepressants, particularly agitated patients or those developing increase of energy together with suicidal thoughts before remission occurs will normally need initial comedication (1 to 4 weeks) with an effective sedating drug such as a benzodiazepine, barbiturate or neuroleptic. Additionally, hospitalisation of these patients is desirable (close observation possible). These measures to lower the risk of suicide should be continued until remission of depression is stable.

Abuse and addiction potential

Abuse of tianeptine is rare and only seen thus far in a few patients with pre-existing multi-substance abuse disorders. One patient reportedly consumed a total of two hundred and forty 12.5 mg tablets (3000 mg) per day for several months and was later successfully detoxified in an inpatient setting. The report indicated that a tolerance was developed and there were physical withdrawal symptoms.[22] However, in 2007, according to the French Health Products Safety Agency (Afssaps),[23] Servier agreed to modify the label of its antidepressant Stablon/Coaxil (tianeptine) following problems of dependency. One hundred forty-one (141) cases of abuse were identified between 1989 and 2004, which correlates to an incidence of 1 to 3 cases per 1000 patients treated with tianeptine. The main reason for abuse is to achieve an anxiolytic effect. According to Servier, cessation of treatment is difficult due to the possibility of withdrawal symptoms.[24][25] Singapore's Ministry of Health has restricted the use of tianeptine to psychiatrists due to its abuse potential, while Bahrain has classified it a controlled substance due to increasing reports of misuse and abuse by patients.[26][27] Tianeptine, under the Coaxil brand name, has been intravenously injected by drug users in Armenia and Russia.[28][29] This method of administration reportedly causes an opiate-like effect, and is sometimes used in an attempt to lessen opiate withdrawal symptoms.[28] As the tablets did not fully dissolve and often the solution is not filtered well, the particles contained in the injected fluid block small blood vessels, leading to thrombosis, then severe necrosis.

References

  1. ^ a b c Royer RJ, Albin H, Barrucand D, Salvadori-Failler C, Kamoun A (1988). "Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors". Clinical Neuropharmacology 11 (Suppl 2): S90–6. PMID 3180120.   List of Library Holdings Worldwide
  2. ^ Invernizzi R e.a. (1992). "Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism". Neuropharmacology 3: 211–7.   |url= http://www.tianeptine.com/dopamine-nacc.html }}
  3. ^ Menza MA, Kaufman KR, Castellanos A (May 2000). "Modafinil augmentation of antidepressant treatment in depression". J Clin Psychiatry 61 (5): 378–81. PMID 10847314.  
  4. ^ Mitchell PB (1995). "Novel French antidepressants not available in the United States". Psychopharmacol Bull 31 (3): 509–19. PMID 8668756.  
  5. ^ PMID: 18072812
  6. ^ Schruers, Koen; Eric Griez (2004). "The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder". Journal of Psychopharmacology 18 (4): 553–8. doi:10.1177/0269881104047283. PMID 15582922. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15582922&dopt=ExternalLink.  
  7. ^ a b Lechin F, van der Dijs B, Orozco B, Jara H, Rada I, Lechin ME, Lechin AE (1998). "The serotonin uptake-enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind, crossover, placebo-controlled study". Journal of Clinical Pharmacology 38 (10): 918–25. PMID 9807972.   Fulltext options (subscription required) List of Library Holdings Worldwide
  8. ^ Lechin F, van der Dijs B, Orozco B, Lechin M, Lechin AE (1996). "Increased levels of free serotonin in plasma of symptomatic asthmatic patients". Annals of Allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology 77 (3): 245–53. PMID 8814052.   List of Library Holdings Worldwide
  9. ^ Lechin F, van der Dijs B, Lechin AE (2004). "Treatment of bronchial asthma with tianeptine". Methods and Findings in Experimental and Clinical Pharmacology 26 (9): 697–701. doi:10.1358/mf.2004.26.9.872567.  
  10. ^ El-Shafey, Hany; Ahmad Atteya, Samir Abu el-Magd, Ahmad Hassanein, Ahmad Fathy, and Rany Shamloul (2005). "Tianeptine Can Be Effective in Men with Depression and Erectile Dysfunction". Journal of Sexual Medicine 3 (0): 910. doi:10.1111/j.1743-6109.2005.00141.x. http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1743-6109.2005.00141.x.  
  11. ^ Uzbay TI (May 2008). "Tianeptine: potential influences on neuroplasticity and novel pharmacological effects". Progress in Neuro-psychopharmacology & Biological Psychiatry 32 (4): 915–24. doi:10.1016/j.pnpbp.2007.08.007. PMID 17826881.  
  12. ^ [1][2]
  13. ^ http://www.pharmoscorp.com/development/tianeptine.html
  14. ^ PMID: 17457538
  15. ^ PMID: 16329631
  16. ^ Eur Psychiatry. 2006 Apr;21(3):174-9. Epub 2005 Jun 17. A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder PMID: 15964747
  17. ^ Les Labotoires Servier (2005). "STABLON (Tianeptine) - Summary of Product Characteristics". STABLON (Tianeptine) - OVERVIEW. Servier International. http://www.servier.com/pro/Neurosciences/stablon/stablon_spc.asp. Retrieved 8 October 2005.  
  18. ^ "Google search of The National Center for Biotechnology Information website for articles containing "tianeptine" and "prenatal"". http://www.google.com/search?hl=en&lr=&safe=off&client=firefox-a&rls=org.mozilla%3Aen-US%3Aofficial&q=site%3Ancbi.nlm.nih.gov+tianeptine+prenatal&btnG=Search. Retrieved 20 October 2005.  
  19. ^ Costa e Silva JA, Ruschel SI, Caetano D, Rocha FL, da Silva Lippi JR, Arruda S, Ozun M (1997). "Placebo-controlled study of tianeptine in major depressive episodes". Neuropsychobiology 35 (1): 24–9. doi:10.1159/000119326. PMID 9018020.   List of Library Holdings Worldwide
  20. ^ (Turkish) Yıldırım, Sema Gülen; Ayşe Devrim Başterzi and Erol Göka (2004). "Tianeptinin Neden Olduğu Hipomani; Bir Olgu Sunumu / Tianeptine Induced Mania: A Case Report" (PDF). Klinik Psikiyatri Dergisi 7 (4): 177–180. http://www.klinikpsikiyatri.org/pdf/4/7/177.pdf.  
  21. ^ Mennini T, Mocaer E, Garattini S (1987). "Tianeptine, a selective enhancer of serotonin uptake in rat brain". Naunyn-Schmiedeberg's Archives of Pharmacology 336 (5): 478–82. doi:10.1007/BF00169302. PMID 3437921.   List of Library Holdings Worldwide
  22. ^ The Good Drug Guide - BioPsychiatry.com (2006). "A Case of Tianeptine Abuse". http://www.biopsychiatry.com/tianeptine-excess.htm. Retrieved 14 March 2008.  
  23. ^ French Health Products Safety Agency (Afssaps) (2007). "Important Information on Drug: Update of the Summary of Product Characteristics Stablon , 16 May 2007 (French)". http://agmed.sante.gouv.fr/htm/10/filltrpsc/lp070502.htm. Retrieved 24 July 2008.  
  24. ^ APM Health Europe (2007). "Addiction leads to warning on Servier's antidepressant Stablon". http://health.apmnews.com/depechesPublieesDepeches.php?annee=2007&mois=5&jour=21. Retrieved 24 July 2008.  
  25. ^ Dr. Valerie Gibaja (2006). "Use, Drug Abuse and Tianeptine (in French)" (PDF). http://www.chu-toulouse.fr/IMG/pdf/Actes_des_Xemes_rencontres_version_finale.pdf. Retrieved 24 July 2008.  
  26. ^ World Health Organisation (2001). "Pharmaceuticals: Restrictions in use and availability, March 2001" (PDF). http://www.who.int/medicinedocs/pdf/s2203e/s2203e.pdf. Retrieved 24 July 2008.  
  27. ^ World Health Organisation (2003). "Pharmaceuticals: Restrictions in use and availability, April 2003" (PDF). http://whqlibdoc.who.int/hq/2003/EDM_QSM_2003.5.pdf. Retrieved 24 July 2008.  
  28. ^ a b Richard Ives (2008). "Assessment Mission Report for the SCAD V Programme, Component on Prevention and on Media Work" (PDF). http://scadarmenia.org/docs/eng/mission_report_prevention.pdf.  
  29. ^ Flavio Mirella, et al. (2005). "Illicit Drug Trades in the Russian Federation" (PDF). http://www.unodc.org/pdf/russia/Publications/drug%20trends%202005_eng.pdf. Retrieved 4 November 2008.  

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