CHANGES IN THE PROLACTIN RESPONSE TO DEXFENFLURAMINE FOLLOWING TIANEPTINE TREATMENT

Serotonin (5-HT) stimulates prolactin release. In the present study, t he ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pre-treatmen t of volunteers with tianeptine, an antidepressant believed to stimula te presynaptic 5-HT uptake. Following a single-blind, random design, o n each experimental day 10 volunteers, each subjected to each regimen, received 60 mg dexfenfluramine taken with 250 mL water at zero time a nd no other treatment; pre-treatment before dexfenfluramine at zero ti me with 12.5 mg tianeptine at -12, -8 and -2; pre-treatment with 12.5 mg tianeptine t.i.d. for 14 days before the dexfenfluramine challenge; or the dexfenfluramine alone after cessation of 14 days of tianeptine treatment. With dexfenfluramine only and with dexfenfluramine after p re-treatment for 14 days with tianeptine, the median prolactin levels at 3,4 and 5h were significantly higher than the respective median bas eline levels. However, all three median post-dexfenfluramine prolactin levels were significantly lower after the 14-day tianeptine treatment than with dexfenfluramine alone. After acute pre-treatment with tiane ptine, the median baseline level of prolactin was significantly higher and the 5 h level significantly lower than with dexfenfluramine alone . The median 5h level after acute tianeptine pre-treatment was also si gnificantly lower than at median baseline. The finding of a blunted pr olactin response, as demonstrated previously with fluoxetine, raises t he possibility that both tianeptine and the 5-HT reuptake inhibitors a ct by decreasing net overall serotonergic transmission. The results ar e not inconsistent with tianeptine enhancing serotonin reuptake. As th e latter has also been demonstrated after multiple doses with antidepr essants such as fluvoxamine, this suggests that the mechanism of tiane ptine may not, in fact, be paradoxical.