Iniesta, Raquel and Hodgson, Karen and Stahl, Daniel and Malki, Karim and Maier, Wolfgang and Rietschel, Marcella and Mors, Ole and Hauser, Joanna and Henigsberg, Neven and Dernovsek, Mojca Zvezdana and Souery, Daniel and Dobson, Richard and Aitchison, Katherine J. and Farmer, Anne and McGuffin, Peter and Lewis, Cathryn M. and Uher, Rudolf (2018) Antidepressant drug-specific prediction of depression treatment outcomes from genetic and clinical variables. Scientific Reports, 8 (1). p. 5530. ISSN 2045-2322
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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.
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| Additional Information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2018 | ||||||||||||||||||||||||||||||||||||
| Departments: | Hrvatski institut za istraživanje mozga Katedra za psihijatriju i psihološku medicinu |
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| Depositing User: | Anja Majstorović | ||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||
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| Date: | 3 April 2018 | ||||||||||||||||||||||||||||||||||||
| Date Deposited: | 26 Jun 2019 08:57 | ||||||||||||||||||||||||||||||||||||
| Last Modified: | 25 Aug 2020 08:05 | ||||||||||||||||||||||||||||||||||||
| Subjects: | / | ||||||||||||||||||||||||||||||||||||
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| URI: | http://medlib.mef.hr/id/eprint/3308 |
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