Routine treatment addition or switch not advisable in MDD patients showing early nonresponse

Major depressive disorder (MDD) patients who do not respond at the second week of treatment with mirtazapine monotherapy, paroxetine monotherapy or their combination appear to show improvements at the eighth week of treatment, according to a study. The data do not support recommendations to routinely offer additional treatment or a switch in treatment strategy to patients who exhibit nonresponse early in the treatment.

The study randomized 204 adult patients with MDD of at least moderate severity who had not achieved early improvement on paroxetine during a 2-week open-label phase trial. These patients who randomly assigned to receive mirtazapine plus placebo (n=68), paroxetine plus placebo (n=68) or mirtazapine plus paroxetine (n=68), with 164 patients completing the outcome assessment.

The primary endpoint of Hamilton Rating Scale for Depression 17-item (HAMD-17) scores at week 8 did not significantly differ across the three treatment groups. The mean changes in HAMD-17 scores were 12.98 points in the mirtazapine group, 12.50 points in the paroxetine group and 13.27 points in the combination group.

The average time to response was shortest in the combination group at 4.9 weeks, followed by the mirtazapine group at 5.2 weeks and the paroxetine group at 5.4 weeks. The corresponding average times to remission were 5.5, 5.4 and 5.6 weeks, respectively. The overall log-rank test of the time to response and remission in the Kaplan–Meier analysis did not achieve significance (p=0.119 and p=0.444, respectively).

Participants on paroxetine monotherapy were least likely to experience adverse effects.

The findings provide no evidence the combination of mirtazapine plus paroxetine outperforms its monotherapy counterparts in the treatment of MDD patients who are early nonresponders to paroxetine, researchers said.

The researchers advised against switching patients who do not exhibit improvement after 2 weeks of monotherapy to combination treatment, adding that patients should continue to wait to assess response after a period of adequate duration with adequate dose as suggested in treatment guidelines.