Research

Computational Psychiatry & Decision-making

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Abstracts

  • Personalized prediction of antidepressant versus placebo response: Evidence from the EMBARC study.
  • Webb CA, Trivedi MD, Cohen C, Dillon DG, Fournier F, Goer F., Fava M, McGrath PJ, Weissman M, Parsey R, Adams P, Trombello JM, Cooper C, Deldin P, Oquendo MA, McInnis MG, Huys Q, Bruder G, Kurian B, Jha M, DeRubeis RJ, and Pizzagalli DA
  • Psychological Medicine (2018). In Press.
  • Background: Major Depressive Disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia and cognitive control deficits. Methods: Within an eight-week multisite trial of sertraline vs. placebo for depressed adults (n =216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics. Results: Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage (post-treatment Hamilton Rating Scale for Depression [HRSD] difference # 3) with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d =.15), those identified as optimally suited to sertraline at pre- treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7)(d =.58). Conclusions: A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.