Paroxetine—The Antidepressant from Hell? Probably Not, But Caution Required
Bibliographic record
Abstract
Paroxetine, also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin and Brisdelle, was first marketed in the U.S. in 1992. Effective for major depression and various anxiety disorders, it quickly gained a sizable share of the antidepressant prescription market. By the late 1990s, paroxetine frequently was being associated with serious drug interactions and medication side effects. Most significantly, in a major Canadian epidemiological study examining the relationship between antidepressants and diseases, paroxetine was associated with a 620 percent increase in the rate of breast cancer in women who had taken it over a four-year period. Though re-analyses of this investigation discounted the magnitude of these findings, other studies have associated paroxetine with numerous side effects and adverse events not reported in clinical trials. Among these are effects on male fertility, birth defects, gestational hypertension, prolonged QT interval in infants, hyperprolactinemia, cognitive impairment in the elderly, autism, sexual side effects, weight gain, and suicidality, aggression, and akathisia in children and adolescents. Paroxetine has the highest inhibitory constant for the P450 2D6 isoenzyme of all antidepressants (Ki = 0.065-4.65 micromoles). This high affinity explains its high inhibitory interaction profile with substrates for 2D6. Paroxetine's potent 2D6 inhibition also implies that significant inhibition of the metabolism of 2D6 carcinogen substrates occurs which implies an increased probability of oncogenesis. Through 2D6 inhibition, tamoxifen metabolism is inhibited, which has been found to increase the risk of dying from breast cancer over a five-year period in women on both medications. Paroxetine also is a potent inhibitor of 3A4 with multiple 3A4 substrate interactions. Paroxetine has the highest known affinity for the serotonin transporter (0.13 nanomoles) of any currently used antidepressant. These characteristics and their potential negative consequences along with other adverse effects are considered and weighed against paroxetine's efficacious antidepressant and anxiolytic effects.
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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 | 0.004 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.002 | 0.004 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.006 | 0.012 |
| Insufficient payload (model declined to judge) | 0.006 | 0.007 |
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".