Tianeptine

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Tianeptine
Systematic (IUPAC) name
7-((3-Chloro-6,11-dihydro-6-methyldibenzo(c,f)

(1,2)thiazepin-11-yl)amino)heptanoic acid S,S-dioxide
Identifiers
CAS number 66981-73-5
ATC code N06AX14
PubChem 68870
Chemical data
Formula C21H25ClN2O4S 
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 described as a selective serotonin reuptake enhancer (SSRE), structurally similar to the tricyclic antidepressants. Unlike tricyclics, however, it enhances the reuptake of serotonin instead of inhibiting it. Stablon, indicated as a thymoleptic, antagonises the effects of serotonin in the limbic system and the pre-frontal cortex, give rise to a mood elevation, compared to mood blunting associated with SSRIs.

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.[2] Suggested dosage is three times times daily, due to its short duration of action. Tianeptine is synergistic and can be used in conjunction with other stimulants such as modafinil.[3] [4]

Tianeptine is claimed to have 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.

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 as well as in Asia and Latin America.

Contents

[edit] Uses

[edit] 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 on paroxetine (Paxil) or tianeptine (Stablon) therapy showed equivalent panic-blocking effects.[5]

[edit] Investigational, off-label, and unapproved

Tianeptine has been reported to be very effective for asthma starting in August of 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.[6] Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic patients.[7] As tianeptine was the only agent known to reduce both 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.[6] By November of 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.[8]

A 2005 study in Egypt demonstrated tianeptine to be effective in men with depression and erectile dysfunction.[9]

A clinical trial in Spain that ended in January of 2007 has shown that tianeptine is effective in treating pain due to fibromyalgia.[1][2]

Tianeptine is also being studied in the treatment of ADD/ADHD.

[edit] Contraindications

According to Servier International, tianeptine is contraindicated in children under 15 years of age, people taking MAOIs, and pregnant or lactating women.[10] However, as of 2005, there are no studies published showing increased risk of birth defects.[11]

[edit] 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.[12]

So far neither seizures nor kidney or bone marrow damage have been noted.

Liver toxicity has been observed very rarely, as is the case with amineptine, however, this is thought to be due to genetic predisposition and is often preceded by rash, itching, fever, and/or abdominal pain.

Sema Gülen Yıldırım and colleagues reported in 2004 of a case of hypomania caused by tianeptine.[13]

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.[14] No data is available regarding effects of the drug on postsynaptic receptors.

[edit] Drug interactions

No sufficient data available at present date.

[edit] Celiac Disease patients

Stablon is gluten and gliadin-free, according to PT. Servier Indonesia.

[edit] Usual doses

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

[edit] 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.

[edit] 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 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. [15]

[edit] See also

[edit] 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. ^ http://brainmeta.com/forum/index.php?s=&showtopic=14231&view=findpost&p=88307
  3. ^ Modafinil augmentation of antidepressant treatment...[J Clin Psychiatry. 2000] - PubMed Result
  4. ^ Novel French antidepressants not available in the ...[Psychopharmacol Bull. 1995] - PubMed Result
  5. ^ 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. PMID 15582922. 
  6. ^ 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
  7. ^ 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
  8. ^ 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. 
  9. ^ 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 0 (0). doi:10.1111/j.1743-6109.2005.00141.x. 
  10. ^ Les Labotoires Servier (2005). STABLON (Tianeptine) - Summary of Product Characteristics. STABLON (Tianeptine) - OVERVIEW. Servier International. Retrieved on 8 October 2005.
  11. ^ Google search of The National Center for Biotechnology Information website for articles containing "tianeptine" and "prenatal". Retrieved on 20 October 2005.
  12. ^ 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
  13. ^ (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. 
  14. ^ 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
  15. ^ The Good Drug Guide - BioPsychiatry.com (2006). A Case of Tianeptine Abuse. Retrieved on 14 March 2008.

[edit] External links

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Psychoanaleptics: antidepressants (N06A)
MAOIs
RIs
SSREs
Tianeptine
AAs