Establishing Evidence for Clinical Utility of a Neuroimaging Biomarker in Major Depressive Disorder: Prospective Testing and Implementation Challenges

Abstract

BackgroundAlthough a number of neuroimaging biomarkers for response have been proposed, none have been tested prospectively for direct effects on treatment outcomes. To the best of our knowledge, this is the first prospective test of the clinical utility of the use of an imaging biomarker to select treatment for patients with major depressive disorder. MethodsEligible participants (n = 60) had a primary diagnosis of major depressive disorder and were assigned to either escitalopram or cognitive behavioral therapy based on fluorodeoxyglucose positron emission tomography activity in the right anterior insula. The overall study remission rate after 12 weeks of treatment, based on the end point Hamilton Depression Rating Scale score, was then examined for futility and benefit of the strategy. ResultsRemission rates demonstrated lack of futility at the end of stage 1 (37%, 10/27), and the study proceeded to stage 2. After adjustment for the change in stage 2 sample size, the complete remission rate did not demonstrate evidence of benefit (37.7%, 95% confidence interval, 26.3%–51.4%, p = .38). However, total remission rates (complete and partial remission) did reach significance in post hoc analysis (49.1%, 95% confidence interval, 37.6%–60.7%, p = .020). ConclusionsThe study shows some evidence for a role of the right anterior insula in the clinical choice of major depressive disorder monotherapy. The effect size, however, is insufficient for the use of insula activity as a sole predictive biomarker of remission. The study also demonstrates the logistical difficulties in establishing clinical utility of biomarkers.