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| C=21 | H=25 | Cl=1 | N=2 | O=4 | S=1
| C=21 | H=25 | Cl=1 | N=2 | O=4 | S=1
| molecular_weight = 436.953 g/mol
| molecular_weight = 436.953 g/mol
| bioavailability= 99 ± 29%<ref name=bioavailable>{{cite journal | author=Royer RJ, Albin H, Barrucand D, Salvadori-Failler C, Kamoun A | title=Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors | journal=Clinical Neuropharmacology | volume=11 | issue=Suppl 2 | year=1988 | pages=S90–6 | pmid=3180120}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=3180120&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]</ref>
| bioavailability= 99 ± 29%<ref name=bioavailable>{{cite journal |author=Royer RJ, Albin H, Barrucand D, Salvadori-Failler C, Kamoun A |title=Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors |journal=Clinical Neuropharmacology |volume=11 Suppl 2 |issue= |pages=S90–6 |year=1988 |pmid=3180120}}</ref>
| metabolism = hepatic
| metabolism = hepatic
| elimination_half-life=2.5 hours (2.5 ± 1.1 h)<ref name=bioavailable />
| elimination_half-life=2.5 hours (2.5 ± 1.1 h)<ref name=bioavailable />
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| excretion = [[Renal]]<ref name=bioavailable />
| excretion = [[Renal]]<ref name=bioavailable />
}}
}}
'''Tianeptine''' ([[International Nonproprietary Name|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 antidepressant]]s, 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<ref>{{cite journal |author=Invernizzi R e.a. |title=Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism |journal=Neuropharmacology |volume=3 |pages=211–7 |year=1992 |url= http://www.tianeptine.com/dopamine-nacc.html }}</ref> and modulates the D<sub>2</sub> and D<sub>3</sub> dopamine receptors<ref>[http://www.tianeptine.com/dopamined2d3.html]</ref>. There is also action on the NMDA and AMPA receptors.
'''Tianeptine''' ([[International Nonproprietary Name|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 antidepressant]]s, 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<ref>{{cite journal |author=Invernizzi R, Pozzi L, Garattini S, Samanin R |title=Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism |journal=Neuropharmacology |volume=31 |issue=3 |pages=221–7 |year=1992 |month=March |pmid=1630590}}</ref> and modulates the D<sub>2</sub> and D<sub>3</sub> dopamine receptors.<ref>[http://www.tianeptine.com/dopamined2d3.html]</ref> There is also action on the NMDA and AMPA receptors.


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.
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, [[Survector|amineptine]], whose side effects related to dopamine uptake inhibitor activity resulted in [[Servier]]'s research into tianeptine.{{Citation needed|date=January 2009}} 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]].<ref>{{cite journal |author=Menza MA, Kaufman KR, Castellanos A |title=Modafinil augmentation of antidepressant treatment in depression |journal=J Clin Psychiatry |volume=61 |issue=5 |pages=378–81 |year=2000 |month=May |pmid=10847314 }}</ref><ref>{{cite journal |author=Mitchell PB |title=Novel French antidepressants not available in the United States |journal=Psychopharmacol Bull |volume=31 |issue=3 |pages=509–19 |year=1995 |pmid=8668756 }}</ref>
Its short-lived, but pleasant, [[stimulant]] effect experienced by some patients is shared with its predecessor, [[Survector|amineptine]], whose side effects related to dopamine uptake inhibitor activity resulted in [[Servier]]'s research into tianeptine.{{Citation needed|date=January 2009}} 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]].<ref>{{cite journal |author=Menza MA, Kaufman KR, Castellanos A |title=Modafinil augmentation of antidepressant treatment in depression |journal=The Journal of Clinical Psychiatry |volume=61 |issue=5 |pages=378–81 |year=2000 |month=May |pmid=10847314}}</ref><ref>{{cite journal |author=Mitchell PB |title=Novel French antidepressants not available in the United States |journal=Psychopharmacology Bulletin |volume=31 |issue=3 |pages=509–19 |year=1995 |pmid=8668756}}</ref>


Tianeptine has 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 drug]]s.<ref>{{cite pmid|18072812}}</ref>
Tianeptine has 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 drug]]s.<ref>{{cite journal |author=Kasper S, McEwen BS |title=Neurobiological and clinical effects of the antidepressant tianeptine |journal=CNS Drugs |volume=22 |issue=1 |pages=15–26 |year=2008 |pmid=18072812 |url=http://content.wkhealth.com/linkback/openurl?issn=1172-7047&volume=22&issue=1&spage=15}}</ref>


Recent interesting results indicate [[anticonvulsant]] and [[analgesic]] activity of tianeptine and its possible interaction with [[adenosine]] A<sub>1</sub> receptors.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/17826881</ref>
Recent interesting results indicate [[anticonvulsant]] and [[analgesic]] activity of tianeptine and its possible interaction with [[adenosine]] A<sub>1</sub> receptors.<ref>{{cite journal |author=Uzbay TI |title=Tianeptine: potential influences on neuroplasticity and novel pharmacological effects |journal=Progress in Neuro-psychopharmacology & Biological Psychiatry |volume=32 |issue=4 |pages=915–24 |year=2008 |month=May |pmid=17826881 |doi=10.1016/j.pnpbp.2007.08.007}}</ref>


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 Stablon and Tatinol.
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 Stablon and Tatinol.
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==Uses==
==Uses==
===Approved===
===Approved===
Tianeptine shows efficacy against serious depressive episodes ([[major depression]]), comparable to [[amitriptyline]], [[imipramine]] and [[fluoxetine]], but with far 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% [[carbon dioxide|CO<sub>2</sub>]] gas ([[carbogen]]) on [[paroxetine]] (Paxil) or tianeptine (Stablon) therapy showed equivalent panic-blocking effects.<ref name=Schruers_and_Griez_2004>{{cite journal | first = Koen | last = Schruers | coauthors = Eric Griez | title = The effects of tianeptine or paroxetine on 35% CO<sub>2</sub> provoked panic in panic disorder | journal = Journal of Psychopharmacology | volume = 18 | issue = 4 | year = 2004 | pages = 553–8 | pmid = 15582922 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15582922&dopt=ExternalLink | doi = 10.1177/0269881104047283}}</ref>
Tianeptine shows efficacy against serious depressive episodes ([[major depression]]), comparable to [[amitriptyline]], [[imipramine]] and [[fluoxetine]], but with far 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% [[carbon dioxide|CO<sub>2</sub>]] gas ([[carbogen]]) on [[paroxetine]] (Paxil) or tianeptine (Stablon) therapy showed equivalent panic-blocking effects.<ref name=Schruers_and_Griez_2004>{{cite journal |author=Schruers K, Griez E |title=The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder |journal=Journal of Psychopharmacology |volume=18 |issue=4 |pages=553–8 |year=2004 |month=December |pmid=15582922 |doi=10.1177/0269881104047283}}</ref>


===Investigational and ongoing research===
===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.<ref name=Lechin_Fuad_et_al_1998>{{cite journal | author=Lechin F, van der Dijs B, Orozco B, Jara H, Rada I, Lechin ME, Lechin AE | title=The serotonin uptake-enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind, crossover, placebo-controlled study | journal=Journal of Clinical Pharmacology | volume=38 | issue=10 | year=1998 | pages=918–25 | pmid=9807972}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9807972&dopt=ExternalLink Fulltext options] (subscription required) [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9807972&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]</ref> Two years earlier, they had found a close, positive association between free serotonin in [[blood plasma|plasma]] and severity of asthma in symptomatic patients.<ref name=Lechin_Fuad_et_al_1996>{{cite journal | author=Lechin F, van der Dijs B, Orozco B, Lechin M, Lechin AE | title=Increased levels of free serotonin in plasma of symptomatic asthmatic patients | journal=Annals of Allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology | volume=77 | issue=3 | year=1996 | pages=245–53 | pmid=8814052}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=8814052&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]</ref> 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.<ref name=Lechin_Fuad_et_al_1998 /> 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.<ref name=By_2004>{{cite journal | author=Lechin F, van der Dijs B, Lechin AE | title=Treatment of bronchial asthma with tianeptine | journal= Methods and Findings in Experimental and Clinical Pharmacology | volume=26 | issue=9 | year=2004 | pages=697–701 | doi=10.1358/mf.2004.26.9.872567}}</ref> A 2005 study in Egypt demonstrated tianeptine to be effective in men with depression and [[erectile dysfunction]].<ref name=erectile_dysfunction>{{cite journal | first = Hany | last = El-Shafey | coauthors = Ahmad Atteya, Samir Abu el-Magd, Ahmad Hassanein, Ahmad Fathy, and Rany Shamloul | year = 2005 | title = Tianeptine Can Be Effective in Men with Depression and Erectile Dysfunction | journal = Journal of Sexual Medicine | volume = 3 | issue = 0 | doi = 10.1111/j.1743-6109.2005.00141.x | url = http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1743-6109.2005.00141.x | pages = 910}}</ref> Tianeptine also has [[anticonvulsant]] and [[analgesic]] effects,<ref name="pmid17826881">{{cite journal |author=Uzbay TI |title=Tianeptine: potential influences on neuroplasticity and novel pharmacological effects |journal=Progress in Neuro-psychopharmacology & Biological Psychiatry |volume=32 |issue=4 |pages=915–24 |year=2008 |month=May |pmid=17826881 |doi=10.1016/j.pnpbp.2007.08.007 |url= |issn=}}</ref> and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to [[fibromyalgia]].<ref>[http://www.controlled-trials.com/ISRCTN16400909/][http://www.institutferran.es/investigacion.htm]</ref> Tianeptine is also being studied in the treatment of [[Attention-deficit hyperactivity disorder|ADD/ADHD]].
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.<ref name=Lechin_Fuad_et_al_1998>{{cite journal |author=Lechin F, van der Dijs B, Orozco B, ''et al.'' |title=The serotonin uptake-enhancing drug tianeptine suppresses asthmatic symptoms in children: a double-blind, crossover, placebo-controlled study |journal=Journal of Clinical Pharmacology |volume=38 |issue=10 |pages=918–25 |year=1998 |month=October |pmid=9807972 |url=http://jcp.sagepub.com/cgi/pmidlookup?view=long&pmid=9807972}}</ref> Two years earlier, they had found a close, positive association between free serotonin in [[blood plasma|plasma]] and severity of asthma in symptomatic patients.<ref name=Lechin_Fuad_et_al_1996>{{cite journal |author=Lechin F, van der Dijs B, Orozco B, Lechin M, Lechin AE |title=Increased levels of free serotonin in plasma of symptomatic asthmatic patients |journal=Annals of Allergy, Asthma & Immunology |volume=77 |issue=3 |pages=245–53 |year=1996 |month=September |pmid=8814052}}</ref> 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.<ref name=Lechin_Fuad_et_al_1998 /> 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.<ref name=By_2004>{{cite journal | author=Lechin F, van der Dijs B, Lechin AE | title=Treatment of bronchial asthma with tianeptine | journal= Methods and Findings in Experimental and Clinical Pharmacology | volume=26 | issue=9 | year=2004 | pages=697–701 | doi=10.1358/mf.2004.26.9.872567}}</ref> A 2005 study in Egypt demonstrated tianeptine to be effective in men with depression and [[erectile dysfunction]].<ref name=erectile_dysfunction>{{cite journal |author=El-Shafey H, Atteya A, el-Magd SA, Hassanein A, Fathy A, Shamloul R |title=Tianeptine can be effective in men with depression and erectile dysfunction |journal=The Journal of Sexual Medicine |volume=3 |issue=5 |pages=910–7 |year=2006 |month=September |pmid=16942535 |doi=10.1111/j.1743-6109.2005.00141.x}}</ref> Tianeptine also has [[anticonvulsant]] and [[analgesic]] effects,<ref name="pmid17826881">{{cite journal |author=Uzbay TI |title=Tianeptine: potential influences on neuroplasticity and novel pharmacological effects |journal=Progress in Neuro-psychopharmacology & Biological Psychiatry |volume=32 |issue=4 |pages=915–24 |year=2008 |month=May |pmid=17826881 |doi=10.1016/j.pnpbp.2007.08.007}}</ref> and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to [[fibromyalgia]].<ref>[http://www.controlled-trials.com/ISRCTN16400909/][http://www.institutferran.es/investigacion.htm]</ref> Tianeptine is also being studied in the treatment of [[Attention-deficit hyperactivity disorder|ADD/ADHD]].


It is currently being researched for its effectiveness in irritable bowel syndrome.<ref>http://www.pharmoscorp.com/development/tianeptine.html</ref>
It is currently being researched for its effectiveness in irritable bowel syndrome.<ref>http://www.pharmoscorp.com/development/tianeptine.html</ref>


Tinaneptine has been found to be effective in depression in Parkinson's disease<ref>{{cite pmid|17457538}}</ref> and in [[post-traumatic stress disorder]]<ref>{{cite pmid|16329631}}</ref> of which it was as safe and effective as fluoxetine (Prozac, an SSRI) and moclobemide (Aurorix, an MAO-A inhibitor)<ref>{{cite pmid|15964747}}</ref>
Tinaneptine has been found to be effective in depression in Parkinson's disease<ref>{{cite journal |author=Levin OS |title=Coaxil (tianeptine) in the treatment of depression in Parkinson's disease |journal=Neuroscience and Behavioral Physiology |volume=37 |issue=4 |pages=419–24 |year=2007 |month=May |pmid=17457538 |doi=10.1007/s11055-007-0029-0}}</ref> and in [[post-traumatic stress disorder]]<ref>{{cite journal |author=Aleksandrovskiĭ IuA, Avedisova AS, Boev IV, ''et al.'' |title=[Efficacy and tolerability of coaxil (tianeptine) in the therapy of posttraumatic stress disorder] |language=Russian |journal=Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova |volume=105 |issue=11 |pages=24–9 |year=2005 |pmid=16329631}}</ref> of which it was as safe and effective as fluoxetine (Prozac, an SSRI) and moclobemide (Aurorix, an MAO-A inhibitor).<ref>{{cite journal |author=Onder E, Tural U, Aker T |title=A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder following an earthquake |journal=European Psychiatry |volume=21 |issue=3 |pages=174–9 |year=2006 |month=April |pmid=15964747 |doi=10.1016/j.eurpsy.2005.03.007}}</ref>
<!--==Mechanism of Action==
<!--==Mechanism of Action==
==Metabolism==-->
==Metabolism==-->


==Contraindications==
==Contraindications==
According to Servier International, tianeptine is contraindicated in children under 15 years of age, people taking [[MAOI]]s, and pregnant or lactating women.<ref name=spc_con>{{cite web | author=Les Labotoires Servier | year=2005 | title=STABLON (Tianeptine) - Summary of Product Characteristics | work=STABLON (Tianeptine) - OVERVIEW | publisher=Servier International | url=http://www.servier.com/pro/Neurosciences/stablon/stablon_spc.asp | accessdate=8 October 2005 | dateformat=dmy}}</ref> However, as of 2005, there are no studies published showing increased risk of birth defects.<ref name=As_of_2005>{{cite web | title=Google search of The National Center for Biotechnology Information website for articles containing "tianeptine" and "prenatal" | url=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 | accessdate=20 October 2005 | dateformat=dmy }}</ref>
According to Servier International, tianeptine is contraindicated in children under 15 years of age, people taking [[MAOI]]s, and pregnant or lactating women.<ref name=spc_con>{{cite web | author=Les Labotoires Servier | year=2005 | title=STABLON (Tianeptine) - Summary of Product Characteristics | work=STABLON (Tianeptine) - OVERVIEW | publisher=Servier International | url=http://www.servier.com/pro/Neurosciences/stablon/stablon_spc.asp | accessdate=8 October 2005 | dateformat=dmy}}</ref> However, as of 2005, there are no studies published showing increased risk of birth defects.<ref name=As_of_2005>{{cite web | title=Google search of The National Center for Biotechnology Information website for articles containing "tianeptine" and "prenatal" | url=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 | accessdate=20 October 2005 | dateformat=dmy }}{{rs}}</ref>


==Side effects==
==Side effects==
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*[[Insomnia]] and vivid dreams (7% vs 20%)
*[[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.<ref name=more_headaches>{{cite journal | author=Costa e Silva JA, Ruschel SI, Caetano D, Rocha FL, da Silva Lippi JR, Arruda S, Ozun M | title=Placebo-controlled study of tianeptine in major depressive episodes | journal=Neuropsychobiology | volume=35 | issue=1 | year=1997 | pages=24–9 | pmid=9018020 | doi=10.1159/000119326}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9018020&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]</ref>
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.<ref name=more_headaches>{{cite journal |author=Costa e Silva JA, Ruschel SI, Caetano D, ''et al.'' |title=Placebo-controlled study of tianeptine in major depressive episodes |journal=Neuropsychobiology |volume=35 |issue=1 |pages=24–9 |year=1997 |pmid=9018020}}</ref>


Sema Gülen Yıldırım and colleagues reported in 2004 of a case of hypomania caused by tianeptine.<ref name=mania>{{tr icon}} {{cite journal | first = Sema Gülen | last = Yıldırım | coauthors = Ayşe Devrim Başterzi and Erol Göka | year = 2004 | title = Tianeptinin Neden Olduğu Hipomani; Bir Olgu Sunumu / Tianeptine Induced Mania: A Case Report | journal = Klinik Psikiyatri Dergisi | volume = 7 | issue = 4 | pages = 177–180 | url = http://www.klinikpsikiyatri.org/pdf/4/7/177.pdf | format = PDF}}</ref>
Sema Gülen Yıldırım and colleagues reported in 2004 of a case of hypomania caused by tianeptine.<ref name=mania>{{tr icon}} {{cite journal | first = Sema Gülen | last = Yıldırım | coauthors = Ayşe Devrim Başterzi and Erol Göka | year = 2004 | title = Tianeptinin Neden Olduğu Hipomani; Bir Olgu Sunumu |trans_title=Tianeptine Induced Mania: A Case Report | journal = Klinik Psikiyatri Dergisi | volume = 7 | issue = 4 | pages = 177–180 | url = http://www.klinikpsikiyatri.org/pdf/4/7/177.pdf | format = PDF}}</ref>


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.<ref name=difference>{{cite journal | author=Mennini T, Mocaer E, Garattini S | title=Tianeptine, a selective enhancer of serotonin uptake in rat brain | journal=Naunyn-Schmiedeberg's Archives of Pharmacology | volume=336 | issue=5 | year=1987 | pages=478–82 | pmid=3437921 | doi=10.1007/BF00169302}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=3437921&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]</ref> No data is available regarding effects of the drug on postsynaptic receptors.
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.<ref name=difference>{{cite journal |author=Mennini T, Mocaer E, Garattini S |title=Tianeptine, a selective enhancer of serotonin uptake in rat brain |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |volume=336 |issue=5 |pages=478–82 |year=1987 |month=November |pmid=3437921}}</ref> No data is available regarding effects of the drug on postsynaptic receptors.


==Drug interactions==
==Drug interactions==

Revision as of 22:43, 28 February 2010

Coaxil redirects here. For the transmission line for radio frequency signals, see Coaxial cable.
Tianeptine
Clinical data
Routes of
administration		Oral
ATC code
Pharmacokinetic data
Bioavailability99 ± 29%[1]
Metabolismhepatic
Elimination half-life2.5 hours (2.5 ± 1.1 h)[1]
ExcretionRenal[1]
Identifiers
  • 7-(3-Chloro-6-methyl-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.131.750 100.069.844, 100.131.750 Edit this at Wikidata
Chemical and physical data
FormulaC21H25ClN2O4S
Molar mass436.953 g/mol g·mol−1

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] and modulates the D2 and D3 dopamine receptors.[3] There is also action on the NMDA and AMPA receptors.

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.[citation needed] 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.[4][5]

Tianeptine has 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.[6]

Recent interesting results indicate anticonvulsant and analgesic activity of tianeptine and its possible interaction with adenosine A1 receptors.[7]

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 Stablon and Tatinol.

Uses

Approved

Tianeptine shows efficacy against serious depressive episodes (major depression), comparable to amitriptyline, imipramine and fluoxetine, but with far 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.[8]

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.[9] Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic patients.[10] 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.[9] 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.[11] A 2005 study in Egypt demonstrated tianeptine to be effective in men with depression and erectile dysfunction.[12] Tianeptine also has anticonvulsant and analgesic effects,[13] and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to fibromyalgia.[14] Tianeptine is also being studied in the treatment of ADD/ADHD.

It is currently being researched for its effectiveness in irritable bowel syndrome.[15]

Tinaneptine has been found to be effective in depression in Parkinson's disease[16] and in post-traumatic stress disorder[17] of which it was as safe and effective as fluoxetine (Prozac, an SSRI) and moclobemide (Aurorix, an MAO-A inhibitor).[18]

Contraindications

According to Servier International, tianeptine is contraindicated in children under 15 years of age, people taking MAOIs, and pregnant or lactating women.[19] However, as of 2005, there are no studies published showing increased risk of birth defects.[20]

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):

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.[21]

Sema Gülen Yıldırım and colleagues reported in 2004 of a case of hypomania caused by tianeptine.[22]

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

Drug interactions

No sufficient data available at present date.

Usual doses

The recommended dosage is three tablets daily, one in the morning, one at midday, and one in the evening before the main meals of the day. In chronic alcoholics, whether cirrhotic or not, no alteration of dosage is necessary. In subjects over 70 years of age, and in subjects with renal insufficiency, the dosage should be restricted to two tablets per day.[24]

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.[25] However, in 2007, according to the French Health Products Safety Agency (Afssaps),[26] 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.[27][28] 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.[29][30] Tianeptine, under the Coaxil brand name, has been intravenously injected by drug users in Armenia and Russia.[31][32] This method of administration reportedly causes an opiate-like effect, and is sometimes used in an attempt to lessen opiate withdrawal symptoms.[31] 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Invernizzi R, Pozzi L, Garattini S, Samanin R (1992). "Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism". Neuropharmacology. 31 (3): 221–7. PMID 1630590. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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  4. ^ Menza MA, Kaufman KR, Castellanos A (2000). "Modafinil augmentation of antidepressant treatment in depression". The Journal of Clinical Psychiatry. 61 (5): 378–81. PMID 10847314. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Mitchell PB (1995). "Novel French antidepressants not available in the United States". Psychopharmacology Bulletin. 31 (3): 509–19. PMID 8668756.
  6. ^ Kasper S, McEwen BS (2008). "Neurobiological and clinical effects of the antidepressant tianeptine". CNS Drugs. 22 (1): 15–26. PMID 18072812.
  7. ^ Uzbay TI (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ Schruers K, Griez E (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ a b Lechin F, van der Dijs B, Orozco B; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ 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. 77 (3): 245–53. PMID 8814052. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ El-Shafey H, Atteya A, el-Magd SA, Hassanein A, Fathy A, Shamloul R (2006). "Tianeptine can be effective in men with depression and erectile dysfunction". The Journal of Sexual Medicine. 3 (5): 910–7. doi:10.1111/j.1743-6109.2005.00141.x. PMID 16942535. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ Uzbay TI (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ [2][3]
  15. ^ http://www.pharmoscorp.com/development/tianeptine.html
  16. ^ Levin OS (2007). "Coaxil (tianeptine) in the treatment of depression in Parkinson's disease". Neuroscience and Behavioral Physiology. 37 (4): 419–24. doi:10.1007/s11055-007-0029-0. PMID 17457538. {{cite journal}}: Unknown parameter |month= ignored (help)
  17. ^ Aleksandrovskiĭ IuA, Avedisova AS, Boev IV; et al. (2005). "[Efficacy and tolerability of coaxil (tianeptine) in the therapy of posttraumatic stress disorder]". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova (in Russian). 105 (11): 24–9. PMID 16329631. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  18. ^ Onder E, Tural U, Aker T (2006). "A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder following an earthquake". European Psychiatry. 21 (3): 174–9. doi:10.1016/j.eurpsy.2005.03.007. PMID 15964747. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  19. ^ Les Labotoires Servier (2005). "STABLON (Tianeptine) - Summary of Product Characteristics". STABLON (Tianeptine) - OVERVIEW. Servier International. Retrieved 8 October 2005. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  20. ^ "Google search of The National Center for Biotechnology Information website for articles containing "tianeptine" and "prenatal"". Retrieved 20 October 2005. {{cite web}}: Unknown parameter |dateformat= ignored (help)[unreliable source?]
  21. ^ Costa e Silva JA, Ruschel SI, Caetano D; et al. (1997). "Placebo-controlled study of tianeptine in major depressive episodes". Neuropsychobiology. 35 (1): 24–9. PMID 9018020. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  22. ^ Template:Tr icon Yıldırım, Sema Gülen (2004). "Tianeptinin Neden Olduğu Hipomani; Bir Olgu Sunumu" (PDF). Klinik Psikiyatri Dergisi. 7 (4): 177–180. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |trans_title= ignored (|trans-title= suggested) (help)
  23. ^ 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. PMID 3437921. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Les Laboratoires Servier (2009). "Stablon - Summary of Product Characteristics, March 2009". Retrieved 21 February 2010. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  25. ^ The Good Drug Guide - BioPsychiatry.com (2006). "A Case of Tianeptine Abuse". Retrieved 14 March 2008. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  26. ^ French Health Products Safety Agency (Afssaps) (2007). "Important Information on Drug: Update of the Summary of Product Characteristics Stablon , 16 May 2007 (French)". Retrieved 24 July 2008. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  27. ^ APM Health Europe (2007). "Addiction leads to warning on Servier's antidepressant Stablon". Retrieved 24 July 2008. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  28. ^ Dr. Valerie Gibaja (2006). "Use, Drug Abuse and Tianeptine (in French)" (PDF). Retrieved 24 July 2008. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  29. ^ World Health Organisation (2001). "Pharmaceuticals: Restrictions in use and availability, March 2001" (PDF). Retrieved 24 July 2008. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  30. ^ World Health Organisation (2003). "Pharmaceuticals: Restrictions in use and availability, April 2003" (PDF). Retrieved 24 July 2008. {{cite web}}: Unknown parameter |dateformat= ignored (help)
  31. ^ a b Richard Ives (2008). "Assessment Mission Report for the SCAD V Programme, Component on Prevention and on Media Work" (PDF). Retrieved 4 November 2008.
  32. ^ Flavio Mirella; et al. (2005). "Illicit Drug Trades in the Russian Federation" (PDF). Retrieved 4 November 2008. {{cite web}}: Explicit use of et al. in: |author= (help)

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