Torsade de Pointes: How Much Do Psychotropics Really Contribute?
Bibliographic record
Abstract
Introduction Based on potential risk of torsade de pointes (TdeP; a rare arrhythmia), regulatory agencies have issue warning for two specific antidepressants. This has translated in clinic as a class effect in that every antidepressant monography or guideline warns against this side effect. Current data suggest that excessive caution in the face of this undesirable effect could have a deleterious effect on mortality. Most research on antidepressant/antipsychotic drugs and TdeP is based on its intermediate marker, the corrected QT interval (QTc) on the electrocardiogram, or case reports. Objectives Our objective is to measure the contribution of psychotropic drugs (antidepressants and antipsychotics) to the arrhythmia itself, and measure its weight among all other risk factors. Methods We completed a retrospective case-control study at the Montreal Heart Institute, with a 1:3 ratio (n=440). We performed hierarchical logistic regression for TdeP (cases vs controls), and included the following independent variables: sex, age, hypokalemia, acute myocardial infarction, left ventricular dysfunction, hepatic failure and/or renal failure, other QTc-prolonging drugs, and psychotropic drugs. We then calculated population attributable risks (PAR). Results In our final model which adjust risk factors for one another, women, acute myocardial infarction, hypokalemia, left ventricular dysfunction, QTc-prolonging drugs, and use of ≥2 antidepressants were significantly associated with TdeP. Age, hepatic and/or renal failure and antidepressants/antipsychotic drug monotherapy were not. The PAR for use of ≥2 antidepressants was 6.3%, while those of other QTc-prolonging drugs, female sex, and left ventricular dysfunction were 55.1%, 41.8%, and 25.6%, respectively. Conclusions When adjusting for concomitant risk factors, monotherapy with antidepressant or antipsychotic drugs is not associated with TdeP. On its side, the use of ≥2 antidepressants is associated with TdeP, with a PAR of lesser magnitude than sex, left ventricular dysfunction, and other QTc-prolonging drugs. This research provides a more nuanced perspective on the relationship between psychotropic drugs and the occurrence of this arrhythmia. Disclosure of Interest None Declared
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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 source (direct Gemma or distilled Codex), 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".