INITIAL INCREASE OF PLASMA SEROTONIN - A BIOLOGICAL PREDICTOR FOR THEANTIDEPRESSANT RESPONSE TO CLOMIPRAMINE

Hypofunction of the serotonin (5-HT) system might be involved in depre ssion. Initial effects of the 5-HT reuptake inhibitor clomipramine (CM I) on plasma 5-HT have never been assessed. On Day 1, 27 depressed pat ients received either a 25-mg CMI slow infusion or a 25-mg CMI tablet in a randomized, double-blind double-dummy design. The daily dose was subsequently titrated up to 75 mg i.v. or 150 mg orally. The Montgomer y-Asberg Depression Rating Scale (MADRS) was rated on Days 1, 4, 7 and 14. High-performance liquid chromatography (HPLC-EC) assays of plasma 5-HT, platelet 5-HT, and CMI were performed on Day I before and after the infusion. On Day I, both groups experienced a mean (nonsignifican t) plasma 5-HT increase; in the i.v. group this initial increase corre lated with MADRS decrease over 14 days (r = 0.76, p =.0025). Correlati ons between platelet 5-HT and MADRS decrease were not significant, The se preliminary data show that: i) CMI administration results in initia l changes in plasma 5-HT; and ii) i.v. CMI-induced initial plasma 5-HT increase is consistent with the CMI 5-HT profile, and might predict t he clinical response to CMI.