The effect of treatment with a new antidepressant, INN 00835, on platelet serotonin uptake in depressed patients

Background: INN 00835 (4-fluoro-L-phenylalanyl-trans-4-hydroxy-L-prolyl-L-a rginyl-glycyl-tryptophanamide ditrifluoroacetate) is a synthetic pentapepti de antidepressant with a potential for rapid onset of action, We were inter ested to see if such action could be correlated with serotonin uptake by pl atelets. Methods: In a phase II clinical trial, unipolar depressed patients were administered active drug, INN 00835 or placebo, subcutaneously, at 0. 2 mg/kg, once daily for 5 consecutive days, Efficacy of treatment was evalu ated by psychometric tests (HAMD, MADS, CSRS, CGI and total VAS). Changes i n platelet uptake rates of serotonin (H-3-5HT) were measured in plasma from the patients participating in the phase II clinical trial, prior to and im mediately after treatment with INN 00835 (19 patients) or placebo (16 patie nts), to evaluate the effect of treatment with INN 00835 on the rate of pla telet 5-HT uptake. Results: The data evaluated by using the psychometric te sts indicated a significant response to treatment with INN 00835 after 5 da ys of dosing. The rates of platelet 5-HT uptake were lower prior to treatme nt (baseline), and increased after the 5-day treatment period. The change i n the uptake rate (Delta V-max) following treatment was significantly large r in the active group than in the placebo group (P < 0.05), The difference between the placebo group and the patients who responded to treatment was e ven larger. Limitations: Small number of subjects. Conclusion: The data ten d to substantiate the use of platelet serotonin uptake as a biochemical mar ker of effective treatment of depression. (C) 1999 Elsevier Science B.V. Al l rights reserved.