Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta-analysis

T. A. Furukawa, K. Maruo, H. Noma, S. Tanaka, H. Imai, K. Shinohara, K. Ikeda, S. Yamawaki, S. Z. Levine, Y. Goldberg, S. Leucht, A. Cipriani

Research output: Contribution to journalArticlepeer-review


Objective : The role of baseline severity as effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This study aims to examine whether baseline severity modifies the efficacy of various antidepressants for major depression through individual participant data (IPD) meta-analysis. Method: We identified all placebo-controlled, double-blind randomised trials of new generation antidepressants in the acute phase treatment of major depression conducted in Japan and requested their IPD through the public–private partnerships (PPPs) between the relevant academic societies and the pharmaceutical companies. The effect modification by baseline depression severity was examined through six increasingly complex competing mixed-effects models for repeated measures. Results: We identified eleven eligible trials and obtained IPD from six, which compared duloxetine, escitalopram, mirtazapine, paroxetine or bupropion against placebo (total n = 2464). The best-fitting model revealed that the interaction between baseline severity and treatment was not statistically significant (coefficient = −0.04, 95% confidence interval: −0.16 to 0.08, P = 0.49). Several sensitivity analyses confirmed the robustness of the findings. Conclusion: We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.

Original languageEnglish
Pages (from-to)450-458
Number of pages9
JournalActa Psychiatrica Scandinavica
Issue number6
StatePublished - Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


  • antidepressives
  • depression
  • meta-analysis

ASJC Scopus subject areas

  • Psychiatry and Mental health

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