A New Reanalysis of STAR*D Data
How does it inform our current understanding of antidepressants?
A team of research investigators has reanalyzed the patient-level data set of the famous ‘Sequenced Treatment Alternatives to Relieve Depression’ (STAR*D) study, following the analysis plan as specified by the original research protocol and related publications. The analysis by Pigott et al., published earlier this year in BMJ Open, reports substantially lower remission rates than the original STAR*D articles had reported.1
Almost everyone in psychiatry is familiar with the broad details of STAR*D, the largest and longest clinical trial conducted to evaluate medication treatment of depression. See this Wikipedia article for a quick overview, or this 2006 summary paper in American Journal of Psychiatry for scientific results as reported originally. It was conducted across 41 clinical sites (a mix of psychiatric and primary care clinics) funded by the NIMH. The trial had four treatment steps, with different options available in steps 2-4 (with the exception of a very underutilized cognitive behavioral therapy option in step 2, all other interventions were medications). After the four treatment steps, subjects were followed for another 12 months, during which their care was guided by their usual providers and not by the researchers.
Clinical trials, especially those conducted by pharmaceutical companies, rely on volunteers recruited through advertising and exclude patients with medical and psychiatric comorbidities. This limits our ability to generalize those results to “real-world patients.” STAR*D recruited patients who were seeking help in primary care and psychiatric settings and included patients with medical and psychiatric comorbidities. The trial was open-label, and treatment allocation was based on patient preference (it wasn’t randomized).
What most people remember, if they remember anything from the results of STAR*D, is the figure of 67%: after undergoing four treatment steps, 67% of people who completed treatment were in remission from their depression. This statistic is highly cited in academic as well as mainstream publications. In contrast, Pigott et al. reported a cumulative remission rate of 35.0% when using the protocol-stipulated assessment measure and inclusion/exclusion criteria.
What explains this discrepancy? And what does this mean, if anything, for our current understanding and clinical use of antidepressant medications?