Tianeptine

Tianeptine (INN) (Stablon®, Coaxil®, Tatinol®), is described as a selective serotonin reuptake enhancer (SSRE), structurally similar to the tricyclic antidepressants. Unlike the tricyclics, however, it enhances the reuptake of serotonin instead of blocking it. Interestingly, tianeptine along with its two metabolites (S8849, S3139) does not affect uptake of monoamines (i.e. DA, 5-HT, and noradrenaline) in vitro. Results from in vivo studies confirm that monoamine reuptake is enhanced, suggesting a mechanism independent of SERT. No data is available regarding effects of the drug on postsynaptic receptors.

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.

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.

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. Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic patients. 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. 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.

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

Tianeptine is also being studied in the treatment of ADD/ADHD, while a new clinical trial will begin in 2007 for treatment of fibromyalgia.

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

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 nightmares occur more often in tianeptine than in amitriptyline recipients (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.

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.

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 potential
Relatively rare and only seen thus far in a few patients with previous or pre-existing multi-substance abuse disorders. One patient reportedly consumed a total of 240 tablets per day for several months and was later successfully detoxified in an inpatient setting. Singapore has restricted the prescription of tianeptine to psychiatrists. Bahrain has designated tianeptine a controlled substance.