To investigate the antidepressant effect of high-dose milnacipran, we retrospectively compared three groups of inpatients with major depression; those who were given milnacipran >100–150 mg/day (high-dose milnacipran group), those treated with milnacipran at maximum doses of 50–100 mg/day (standard-dose milnacipran group), and those treated with paroxetine at maximum doses of 40 mg/day (paroxetine group). The Hamilton Depression Rating Scale (HAM-D) scores of the three groups showed significant decrease at discharge compared to the scores at admission, indicating improvement of depressive symptoms for each group. However, the mean HAM-D score on admission was significantly lower for the standard-dose milnacipran group than the high-dose milnacipran and paroxetine groups. Additional intermediate assessment of the high-dose milnacipran group showed that the effect of milnacipran was dose-dependent with an additional improvement when patients were increase from 100 to 150 mg/day. These results suggest that patients suffering from moderate to severe depression with relative high HAM-D scores may benefit from treatment with high-dose milnacipran
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