Tianeptine is an effective antidepressant with original neurochemical properties. Tianeptine increases the serotonin (5-HT) reuptake after acute and chronic treatment. The efficacy of tianeptine (T) versus placebo (P) was evaluated in the treatment of psychasthenia, because of the role of 5-HT in obsessive-compulsive disorders, the last state of psychasthenia in term of severity. Patients were recruited using the psychasthenia scale; then, their MADRS scores limited those who turned out to the depression. Mean inclusion MADRS scores where 12 (T) and 11.8 (P). Tianeptine is an effective treatment for patients suffering from psychasthenia. Tianeptine is more effective than placebo in global score and in sub-scores (asthenia and somatic symptoms) of the psychasthenia scale. In spite of weak inclusion scores in MADRS, patients taking tianeptine also showed significant improvement, greater than with placebo. The percentage of patients with a reduction equal to or greater than 50% of their MADRS score was significantly more important in tianeptine group. These results could be the illustration of the decrease in associated depressive symptoms or the result of an improvement of symptoms common to MADRS and psychasthenia scales. The same favorable results were obtained in symptoms of anxiety scored by HARS. In term of safety, tianeptine is equivalent to a placebo if we consider somatic complaints expressed by the patients, global improvement evaluated by the patient and the investigator, weight and blood pressure. Interruption of treatment for side-effects concerns the placebo group only (3 versus 0). This excellent safety is particularly well-adapted to the treatment of these out-patients.