Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study

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 heterog...

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Published in:	Psychological medicine 2019-05, Vol.49 (7), p.1118-1127
Main Authors:	Webb, Christian A., Trivedi, Madhukar H., Cohen, Zachary D., Dillon, Daniel G., Fournier, Jay C., Goer, Franziska, Fava, Maurizio, McGrath, Patrick J., Weissman, Myrna, Parsey, Ramin, Adams, Phil, Trombello, Joseph M., Cooper, Crystal, Deldin, Patricia, Oquendo, Maria A., McInnis, Melvin G., Huys, Quentin, Bruder, Gerard, Kurian, Benji T., Jha, Manish, DeRubeis, Robert J., Pizzagalli, Diego A.
Format:	Article
Language:	eng
Subjects:	Adolescent Adult Aged Algorithms Anhedonia Antidepressants Antidepressive Agents - therapeutic use Artificial intelligence Clinical guidelines Cognition Cognitive ability Demography Depressive Disorder, Major - diagnosis Depressive Disorder, Major - diagnostic imaging Depressive Disorder, Major - psychology Depressive personality disorders Double-Blind Method Endophenotypes Fees & charges Female Funding Grants Hedonic response Humans Individualized Intervention Laboratories Learning Learning algorithms Machine Learning Male Mental depression Middle Aged Neurosis Neuroticism Original Articles Parsing Pathophysiology Patient Outcome Assessment Pharmaceuticals Precision Medicine Prospective Studies Royalties Schizophrenia Science Sertraline Sertraline - therapeutic use Severity Substance abuse treatment Treatment Outcome Validity Variables Young Adult
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Summary:	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. Within an 8-week multisite trial of sertraline v. 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. 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 = 0.15), 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 = 0.58). 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.
ISSN:	0033-2917 1469-8978