Tianeptine 2475030 226152545 2008-07-17T01:39:10Z 24.109.109.31 /* Uses */ {{Drugbox| |IUPAC_name = 7-((3-Chloro-6,11-dihydro-6-methyldibenzo(c,f)<br> ''(1,2)thiazepin-11-yl)amino)heptanoic acid S,S-dioxide | image=Tianeptine.svg | image2=Tianeptine3d.png | CAS_number=66981-73-5 | ATC_prefix=N06 | ATC_suffix=AX14 | ATC_supplemental= | PubChem=68870 | DrugBank= | C=21 | H=25 | Cl=1 | N=2 | O=4 | S=1 | 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> | metabolism = hepatic | elimination_half-life=2.5 hours (2.5 +/- 1.1 h)<ref name=bioavailable /> | pregnancy_AU = | routes_of_administration= Oral | excretion = [[Renal]]<ref name=bioavailable /> }} '''Tianeptine''' ([[International Nonproprietary Name|INN]]) (Stablon, Coaxil, Tatinol), is described as a [[selective serotonin reuptake enhancer]] ([[SSRE]]). Unlike conventional [[tricyclic antidepressant]]s, tianeptine enhances the reuptake of [[serotonin]] instead of inhibiting it, opposite to the action of SSRIs. Tianeptine, indicated as a [[thymoleptic]], antagonises 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. 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.<ref>http://brainmeta.com/forum/index.php?s=&showtopic=14231&view=findpost&p=88307</ref> 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]].<ref>[http://www.ncbi.nlm.nih.gov/pubmed/10847314 Modafinil augmentation of antidepressant treatment...[J Clin Psychiatry. 2000&#93; - PubMed Result<!-- Bot generated title -->]</ref> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/8668756?dopt=Abstract Novel French antidepressants not available in the ...[Psychopharmacol Bull. 1995&#93; - PubMed Result<!-- Bot generated title -->]</ref> 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 drug]]s. 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. The last remaining production (in Latin America) for its predecessor amineptine was discontinued in 2006, leaving tianeptine as the sole antidepressant in Servier's portfolio. ==Uses== ===Approved=== Tianeptine shows efficacy against serious depressive episodes ([[major depression]]), comparable to [[amitriptyline]], [[imipramine]] and [[fluoxetine]], but with fewer side effects. It 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 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> ===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.<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 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.<ref name=Lechin_Fuad_et_al_1998 /> 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.<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> A clinical trial in Spain that ended in January of 2007 has shown that tianeptine is effective in treating pain due to [[fibromyalgia]].[http://www.controlled-trials.com/ISRCTN16400909/][http://www.institutferran.es/investigacion.htm] Tianeptine is also being studied in the treatment of [[Attention-deficit hyperactivity disorder|ADD/ADHD]]. <!--==Mechanism of Action== ==Metabolism==--> ==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 | accessdaymonth=8 October | accessyear=2005}}</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 | accessdaymonth=20 October | accessyear=2005 }}</ref> ==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.<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> 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.<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> 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. ==Drug interactions== No sufficient data available at present date. ==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. ==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 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. <ref>{{cite web | author=The Good Drug Guide - BioPsychiatry.com| year=2006 | title=A Case of Tianeptine Abuse | url=http://www.biopsychiatry.com/tianeptine-excess.htm | accessdaymonth=14 March | accessyear=2008}}</ref> ==See also== *[[amineptine]] *[[serotonin]] *[[antidepressant]] *[[clinical depression]] ==References== {{reflist}} ==External links== *{{cite web | title=Tianeptine: a review of its use in depressive disorders | url=http://www.biopsychiatry.com/tianeptinerev.htm | accessdaymonth=7 October | accessyear=2005 }} * [http://www.servier.com/ Servier Homepage] * [http://www.tianeptine.com/ Tianeptine.com] {{Antidepressants}} [[Category:Selective serotonin reuptake enhancers]] [[pl:Tianeptyna]] [[ru:Тианептин]]