Leo Sher, M.D.

Fifteen years ago, our paper, “Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls” was published in Psychoneuroendocrinology (1). In this study, we compared the prolactin response to fenfluramine administration in unipolar depressed patients (major depressive disorder), depressed patients with bipolar disorder, and healthy controls.

One hundred and fifty-eight depressed patients with unipolar depression (major depressive disorder), 21 patients with bipolar disorder and 32 healthy volunteers participated in the study. Subjects were administered 0.8 mg/kg of d,l-fenfluramine orally at 9 am. Blood samples were drawn 15 min before capsule administration (time -15), at time of administration of the capsule (time 0) and then hourly for 5 h. Blood samples were analyzed for prolactin, fenfluramine, and norfenfluramine levels

We observed a trend towards a blunted prolactin response in depressed patients compared to healthy controls, after controlling for sex, family history, family history-by-gender interaction, and baseline levels. We did not find a significant difference between unipolar and bipolar patients in the baseline prolactin levels or the response to the fenfluramine administration. We also found a negative correlation between aggression and impulsivity scores and prolactin responses in subgroup with unipolar but not bipolar depression. Female patients with unipolar depression who had first-degree relatives with unipolar depression and normal controls had significantly higher prolactin responses than female patients with unipolar depression who did not have first-degree relatives with unipolar depression.

The lack of difference in the response to fenfluramine administration between unipolar and bipolar depressed patients may indicate that overall serotonergic function in unipolar and bipolar depressed patients is similarly impaired. Although we found that overall serotonergic function in unipolar and bipolar depressed patients is similar, we could not exclude the possibility that the impairment of serotonergic function in unipolar and bipolar depressed patients may involve different components of the serotonin system in different brain regions.

Reference

1. Sher L, Oquendo MA, Li S, Ellis S, Brodsky BS, Malone KM, Cooper TB, Mann JJ. Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls. Psychoneuroendocrinology 2003;28(4):559-73.