Risk of adverse events in treatment-resistant depression: Propensity-score-matched comparison of antidepressant augment and switch strategies

Richard A. Hansen, Stacie B. Dusetzina, Alan R. Ellis, Til Stürmer, Joel F. Farley, Bradley N. Gaynes

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Objective: The objective was to assess differences in adverse events between major depressive patients augmented with a second medication and patients switched to an alternative monotherapy after failing first-step treatment with citalopram. Method: Adverse event profiles for second-step switch and augment medication strategies were compared using public data files from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. In the STAR*D trial, participants failing citalopram selected acceptable next-step strategies and were randomized within acceptable strategies. This design resulted in clinically important differences when comparing across strategies, so a propensity-score-matched sample was created to compare switch (n=269) and augment (n=269) strategies. Results: Incidence proportions of any adverse event and specific adverse events were similar between the augment and switch groups. The overall incidence proportion of any distressing event was 0.78 [95% confidence interval (CI) 0.72-0.84] in the augment group and 0.80 (95% CI 0.74-0.85) in the switch group. This contrasts unmatched analyses where distressing adverse events were less common in the augment group than the switch group (risk ratio 0.85, 95% CI 0.81-0.90). Conclusion: After adjusting for selection bias inherent in the STAR*D comparison of augment with switch, clinically meaningful differences in the adverse event profiles between these treatment strategies were not observed.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalGeneral Hospital Psychiatry
Issue number2
StatePublished - Mar 2012

Bibliographical note

Funding Information:
This project was funded under Contract No. HHSA290-2005-0040-I-TO2 from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services (DHHS) , as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by AHRQ or DHHS. Copyright assertion has been provided.


  • Adverse events
  • Augment
  • Major depression
  • Propensity score
  • Switch


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