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

Abstract

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.

Cortisol, ACTH, Prolactin and Beta-Endorphin Responses to Fenfluramine Administration in Major-Depressed Patients

“…These findings consolidate earlier reports [Muhlbauer and Muller-Oerlinghausen, 1985;Asnis et al" 1988;Lopez-Ibor et al, 1988], Furthermore, we found that the secretion of the related pituitary hormones -ACTH and P-endorphins -did not differ between major and minor depressives. These results are at variance with the find ings of Meltzer et al [1984] and Maes et al [1987Maes et al [ , 1989d who found a hyperresponsivity of ACTH and/or cortisol after loading with 5-hydroxytryptophan in major depressives.…”

Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression

“…The reported increases in plasma cortisol response to fenfluramine following lithium treatment (Mannel et al, 1997; Muhlbauer and Muller-Oerlinghausen, 1985) and in the L-5-HTTP-induced cortisol response following divalproex treatment (Maes et al, 1997) in BD patients appear particularly compatible with enhanced post-synaptic 5-HT 1A receptor function. In the case of lithium, the increase in post-synaptic 5-HT 1A receptor BP P fits within the context of increased serotonin release more generally, implying that these changes would interact to enhance post-synaptic 5-HT 1A receptor neurotransmission.…”

Augmenting - Reducing Response to Auditory Evoked Potentials and its Relationship to the Prophylactic Effect of Lithium Salts

“…. hypo thesis that lithium might possibly act by a serotonergic mechanism, it is planned to examine the central serotonergic acitivty by use of the fenfluramine test (13) in the same subjects where also the ASF to auditory stimuli is assessed. Surprisingly, the latencies of the NI and P2 components were significantly shorter in the responders than in the nonresponders.…”