The most commonly prescribed antidepressants are SSRIs, drugs that are supposed to selectively target the neurotransmitter serotonin. But there is another antidepressant that has a very different mode of action. It is called tianeptine, and it has been approved for prescription as an antidepressant by the French drug regulatory agency. Tianeptine is an SSRE, a selective serotonin reuptake enhancer. Instead of increasing the amount of serotonin in the brain, it is supposed to decrease it. If the theory that depression is caused by a deficiency of serotonin were correct, we would expect to make depression worse. But it doesn’t. In clinical trials comparing the effects of tianeptine to those of SSRIs and tricyclic antidepressants, 63% of patients show significant improvement (defined as a 50% reduction in symptoms), the same response rate that is found for SSRIs, NDRIs, and tricyclics, in this type of trial (Wagstaff, Ormrod, & Spencer, 2001). It simply does not matter what is in the medication – it might increase serotonin, decrease it, or have no effect on serotonin at all. The effect on depression is the same. - www.ncbi.nlm.nih.gov