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Emulating a target trial of dynamic treatment strategies for major depressive disorder using data from the STAR*D randomized trial

      Abstract

      Background

      Clinical guidelines recommend adding a second drug for patients with major depressive disorder who have a partial response, and switching antidepressants for those who show no response or intolerance. The authors compared this guidelines-based strategy to other strategies for the management of unresponsive depression.

      Methods

      1436 individuals experiencing treatment failure with citalopram and still requiring antidepressant therapy were identified in the STAR*D trial. A (hypothetical) target trial was then designed and emulated. The following strategies for decision-making were compared: sequential monotherapy (SM), sequential dual non-SSRI (SD), and the guidelines-based. The primary outcome was symptomatic remission, defined as a HDRS score<7 or two consecutive QIDS-C16<5. Secondary outcomes were serious events (hospitalizations, suicide and mortality). Inverse probability weighting was used to control for confounding.

      Results

      971 patients were eligible for our emulation. Patients initiating SD had the lowest levels of depression at baseline. The estimated 9-month probability of remission was 43.5% for SM, 47.6% for SD, and 53.2% for guidelines-based. Compared with SM, the difference in 9-month probability of remission was -4.2% (95%CI: -15.6,4.6) for SD and -9.7% (-19.3,1.9) for guidelines-based. The 9-month relative risks (RR) of remission were 1.09 (0.90,1.38) and 1.22 (0.96,1.46), respectively. Results were consistent across sensitivity analyses. The 9-month RR of serious events were 0.77 (0.38,1.40) and 0.62 (0.33,1.00), respectively.

      Conclusions

      Using the guidelines-based strategy was associated with an increased probability of remission and a lower risk of serious adverse events. The potential implications are substantial given the large number of patients experiencing treatment failure to antidepressants.
      ClinicalTrials.gov (NCT00021528)

      Keywords

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