Antidepressant drug-specific prediction of depression treatment outcomes from genetic and clinical variables
Bibliographic record
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".