Fenfluramine stimulation of serum cortisol in patients with major affective disorders and healthy controls: further evidence for a central serotonergic action of lithium in man.

In order to investigate the influence of lithium long-term medication on serotonergic neurotransmission, fenfluramine stimulation (FFS) was used for the assessment of hormonal effects under serotonergic control. The cortisol plasma concentration following FFS was examined between 8 a.m. and 1 p.m. in 11 manic-depressive subjects under lithium prophylaxis and in 8 untreated euthymic patients. In addition, 11 healthy subjects with FFS, and 12 other subjects without FFS were investigated. The basal cortisol concentrations show considerable variation. Those of the lithium patients were in general found lower than those of the control groups. In both, the controls and the manic-depressive patients without lithium medication, no gross deviation from the expected physiological decline of morning cortisol values was found. A subtle effect of FFS in healthy subjects could be observed. In the lithium patients, however, a significant inversion of the cortisol secretion pattern with a steep increase between 10 and 12 a.m. could be demonstrated. It is concluded that FFS and lithium long-term medication exert an agonistic influence onto central serotonergic neurotransmission. Pharmacological challenge with fenfluramine may prove to be a useful tool for the investigation of serotonergic mechanisms in biological psychiatry.