Fenfluramine challenge in unipolar depression with and without anger attacks

We have previously hypothesized that patients with major depression and anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks. We wanted to compare the prolactin response to fenfluramine challenge, as an indirect measure of central serotonergic function, in depressed patients with and without anger attacks. We recruited 37 outpatients (22 men and 15 women; mean age: 39.5±10.5) with DSM-III-R major depressive disorder, diagnosed with the SCID-P. Their initial 17-item Hamilton Rating Scale for Depression score was ≥16. Patients were classified as either having or not having anger attacks with the Anger Attacks Questionnaire. All patients received a single-blind placebo challenge followed by a fenfluramine challenge (60 mg orally) the next day. Plasma prolactin measurements were obtained with double antibody radioimmunoassay before and after both placebo and fenfluramine challenges, and fenfluramine and norfenfluramine blood levels after each challenge were determined by gas chromatography. Of the 37 study participants, 17 (46%) were classified as having anger attacks. There were no significant differences in age, gender, fenfluramine, or norfenfluramine blood levels between depressed patients with and without anger attacks. Depressed patients with anger attacks showed a significantly blunted prolactin response to fenfluramine challenge compared to patients without anger attacks. As previous studies have shown blunted prolactin responses to fenfluramine in impulsive aggression among patients with personality disorders, our results support our hypothesis that depressed patients with anger attacks may have a relatively greater serotonergic dysregulation than depressed patients without these attacks.