Leo Sher, M.D.

Our research report, “The number of previous depressive episodes is positively associated with cortisol response to fenfluramine administration” was published 20 years ago in December 2004 in the Annals of the New York Academy of Sciences (1).

Multiple reports document hypothalamic-pituitary-axis (HPA) hyperactivity in depressed patients. Measurement of cortisol levels after ingestion of fenfluramine, a specific serotonin releaser/uptake inhibitor agent, provides an index of HPA activity. To our knowledge, our study was the first study of the effect of a number of previous depressive episodes on cortisol responses to fenfluramine administration.

Unipolar depressed patients and healthy volunteers were included in the study. Demographic and clinical parameters were assessed and recorded. Response to fenfluramine administration was measured by the difference between maximum hourly plasma cortisol measurements after fenfluramine administration and baseline levels measured before fenfluramine administration. The number of previous major depressive episodes was a predictor of cortisol response to fenfluramine administration in depressed patients. Higher cortisol responses were associated with more prior episodes of major depression. The relationship of cortisol to the number of previous depressive episodes remained significant after controlling for age. Our finding highlighted the importance of possible cumulative effects of repeated episodes of major depression.

Reference

1. Sher L, Oquendo MA, Galfalvy HC, Cooper TB, Mann JJ. The number of previous depressive episodes is positively associated with cortisol response to fenfluramine administration. Ann N Y Acad Sci. 2004 Dec;1032:283-6. doi: 10.1196/annals.1314.039