Restoring STAR*D: A Reanalysis of Drug-Switch Therapy After Failed SSRI Treatment Using Patient-Level Data with Fidelity to the Original STAR*D Research Protocol.

Abstract

Background: The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial was designed to give guidance in selecting the best next-step treatment for depressed patients who did not remit during their first, and/or subsequent, antidepressant trial, with up to four trials per patient. Our prior research documented protocol violations which inflated STAR*D's reported cumulative remission rate by 91.4%. A similar reanalysis of the step-2 drug-switch trial has not been done until now.

Methods: We reanalyzed the patient-level dataset of STAR*D's drug-switch treatment therapies-with fidelity to the original research protocol and related publications-to determine whether there were clinically-relevant differences in results compared to the original publication.

Results: While our reanalysis largely comported with STAR*D's published findings of no significant differences between drug-switch treatments, we found the following discrepancies: Lower than reported step-2 remission rates ranging from 16.2 to 19.3% (versus 17.6 to 24.8%); A significant increase in treatment-emergent suicidal ideation during the step-2 drug-switch therapies ranging from 11.2 to 15.0% compared to step-1 citalopram treatment (9.0%); A four times greater number of severe suicidal behaviors reported by the treating clinicians compared to the published suicide-related Serious Adverse Events (16 versus 4); and A sustained remission rate of only 3.1 to 8.4%.

Conclusion: Compared to the original publication, our reanalysis found lower remission rates and more suicidal risk than reported. This adds to the discrepancies found in our prior reanalysis and also to the finding that switching antidepressants is not well supported by the evidence.