Milnacipran versus Sertraline in Major Depressive Disorder: A Double-Blind Randomized Comparative Study on the Treatment Effect and cbeta-Adrenergic Receptor Responsiveness

Yang, Jong Chul; Kim, Sung Wan; Yu, Bum Hee

Abstract

OBJECTIVE
This study was aimed to compare the efficacy and tolerability of milnacipran and sertraline treatment in patients with major depressive disorder and to evaluate the relationships between beta-adrenergic receptor responsiveness and depressive mood states. METHODS: Fifty three patients who had a diagnosis of major depressive disorder according to the DSM-IV and showed scores of 17 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to either milnacipran or sertraline treatment group. Each patient received 8 weeks of antidepressant treatment with one of the two drugs. Efficacy was assessed using the HAM-D, Beck Depression Inventory (BDI), Montgomery and Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI). Twenty normal control subjects who had no history of psychiatric and major medical illness and were matched with the depressed patients considering age, sex and body mass index were recruited for the comparison of beta-adrenergic receptor responsiveness between depressed patients and normal control subjects. We measured beta-adrenergic receptor density, lymphocyte cAMP ratio (ratio of isoproterenol-stimulated cAMP/basal cAMP), and receptor affinity (Kd) in all subjects. We also investigated beta-adrenergic receptor responsiveness before and after treatment in depressed patients. RESULTS: Twelve patients in milnacipran group and 15 patients in sertraline group were completed this study. In all assessment scales for depression, we found significant decrease in depression severity in both milnacipran and sertraline groups. Both of the two drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. And there were significant differences in the means of Kd values between control subjects and depressed patients before treatment. We found a significant negative correlation between Kd values and BDI scores. After treatment with either milnacipran or sertraline, cAMP ratio (4.8+/-1.6 vs 5.7+/-2.5, p=0.095) and Kd value (65.6+/-11.9 vs 74.6+/-7.8, p=0.066) tended to increase, but there was no significant difference in beta-adrenergic receptor responsiveness between milnacipran and sertraline group. CONCLUSION: Both milnacipran and sertraline were not different in the clinical efficacy in major depressive disorder. In depressed patients, beta-adrenergic receptor responsiveness is reduced and both milnacipran and sertraline antidepressants tended to increase beta-adrenergic receptor responsiveness.