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

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Dec 1;35(8):1983-9. doi: 10.1016/j.pnpbp.2011.08.008. Epub 2011 Aug 24.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Citalopram / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Drug Substitution
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / therapeutic use
  • Prospective Studies
  • Sertraline / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Antidepressive Agents
  • Citalopram
  • Paroxetine
  • Sertraline