Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial.

RATIONALE

Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.

OBJECTIVES

We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.

METHOD

Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥50% improvement in the MADRS) at week 8.

RESULTS

Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n=20) showed a higher rate of responders than the Continuing group (n=21) (75% vs. 19%: p=0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤10 in the MADRS) (60% vs. 14%: p=0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p<0.001).

CONCLUSIONS

Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.