Oral d-fenfluramine test in treatment-refractory depression: Plasma prolactin response compared in patients with and without suicide attempts and in a healthy reference group

Background: Fenfluramine (d-FEN) has been used as a serotonin challenge agent to assess central serotonin availability. Blunted serum prolactin (PRL) response to d-FEN has been reported in depressed patients, in suicide-prone patients, and in patients with aggression and personality disorders. We have analyzed suicidality in relation to central serotonergic events by comparing the PRL response to d-FEN in chronically depressed patients with and without suicide attempts and in healthy volunteers. Methods: In 56 inpatients (10 patients with and 46 without suicide attempts) with at least 2 years of treatment-refractory depression (TRD) (DSM-IV) and a reference group of 30 healthy adults, the PRL response after an oral dose of 30 mg d-FEN was followed for 5 h. Results: Controlling for group differences in age, sex, and weight, the PRL response to d-FEN did not differ significantly between the three groups. Far from confirming the hypothesis of a blunted PRL response in depressed patients, our results suggest: (1) that duration and treatment resistance of depression may affect the PRL secretion, and (2) that TRD and major depression may differ in biological relationship to suicidal behavior. Limitations: The findings require corroboration in larger and more closely matched study populations. The fenfluramine concentration was not analyzed in blood. Conclusions: PRL responses to d-FEN challenge did not differ between TRD patients with and without suicidality and the healthy reference group. Chronicity/treatment refractoriness per se may be related to a serotonergic mechanism.