CONTROLLED COMPARISON OF MILNACIPRAN AND FLUOXETINE IN MAJOR DEPRESSION

The efficacy and the tolerance of milnacipran (100 mg/day), a second g eneration antidepressant which equipotently inhibits both noradrenalin e and serotonin reuptake, was compared to fluoxetine (20 mg/day), a se lective serotonin reuptake inhibitor, in two parallel groups of, respe ctively, 97 and 93 major depressive outpatients. The duration of the s tudy was 6 weeks, with assessments every 2 weeks by means of the Montg omery and Asberg depression scale (MADRS), the Hamilton depression sca le, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetin e over milnacipran on most rating instruments: MADRS (P = 0.01) includ ing five individual items, Hamilton depression scale (P = 0.002) inclu ding ten individual items, CGI of severity (P = 0.01) and therapeutica l index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psyc hostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of sympt oms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could re sult from the selection of a dose of milnacipran below the optimal the rapeutic dose for this type of psychiatric patients or to the administ ration of the compounds in single daily intakes, whereas milnacipran p ossesses a plasma elimination half-life of only 7 h.