One hundred and sixty-three patients with major depression were randomly assigned to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical trial. Initially, patients received mirtazapine 20 mg/day or doxepin 75 mg/day; dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day, respectively. Both drugs produced considerable improvement in depressive symptoms with no statistically significant differences between the two patient groups. In the mirtazapine group only two patients prematurely terminated the study due to adverse drug experiences, as compared to six in the doxepin-treated group. Moreover, doxepin-treated patients complained more frequently of dry mouth and movement disorders. In conclusion, mirtazapine is an effective treatment for major depression and appears to offer advantages in tolerability over doxepin.