Abstract The onset of action (during the first 2 weeks of treatment) of moclobemide (450 mg/day), a reversible MAO-A inhibitor, was compared in a double-blind, multi-center trial with clomipramine (150 mg/day) on dimensional and global depressive symptoms in 124 hospitalized patients suffering from a major depressive episode according to DSM-III-R criteria and with blunted affect and retardation. An earlier efficacy was found for moclobemide with significant treatment differences in favor of moclobemide, which were detected on negative symptoms (anhedonia, blunted affect and retardation) on days 7 and 10. The overall effect on depression at the end of the 4-week trial period was similar in both groups. However, a higher termination rate due to lack of efficacy was found with moclobemide (10 vs. 3). The tolerability was significantly better for moclobemide, as shown by the lower frequency of adverse events.