Antidepressant drug-specific prediction of depression treatment outcomes from genetic and clinical variables

Raquel Iniesta, Karen Hodgson, Daniel Richard Stahl, Karim Malki, Wolfgang Maier, Marcella Rietschel, Ole Mors, Joanna Hauser, Neven Henigsberg, Mojca Zvezdana Dernovšek, Daniel Souery, Richard Dobson, Katherine. J Aitchison , Anne Farmer, Peter McGuffin, Cathryn M. Lewis, Rudolf Uher

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Abstract

Individuals with depression differ substantially in their response to treatment with antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict who will respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables. Using statistical learning on common genetic variants and clinical information in a training sample of 280 individuals randomly allocated to 12-week treatment with antidepressants escitalopram or nortriptyline, we derived models to predict remission with each antidepressant drug. We tested the reproducibility of each prediction in a validation set of 150 participants not used in model derivation. An elastic net logistic model based on eleven genetic and six clinical variables predicted remission with escitalopram in the validation dataset with area under the curve 0.77 (95%CI; 0.66-0.88; p = 0.004), explaining approximately 30% of variance in who achieves remission. A model derived from 20 genetic variables predicted remission with nortriptyline in the validation dataset with an area under the curve 0.77 (95%CI; 0.65-0.90; p < 0.001), explaining approximately 36% of variance in who achieves remission. The predictive models were antidepressant drug-specific. Validated drug-specific predictions suggest that a relatively small number of genetic and clinical variables can help select treatment between escitalopram and nortriptyline.
Original languageEnglish
Article number5530
Number of pages9
JournalScientific Reports
Volume8
Issue number1
Early online date3 Apr 2018
DOIs
Publication statusPublished - 3 Apr 2018

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