Who Develops Severe or Fatal Adverse Drug Reactions to Selective Serotonin Reuptake Inhibitors?
Why this work is in the frame
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Bibliographic record
Abstract
OBJECTIVE: To ascertain the risk factors associated with the development of severe and fatal adverse drug reactions (ADRs) or intentional overdoses by patients on selective serotonin reuptake inhibitors (SSRIs). METHODS: We undertook a data analysis of Health Canada's database of Adverse Drug Reactions to SSRIs from 1986 to 1996, as well as a literature review. RESULTS: Among the complete ADR reports in the SSRI database, there were no sex differences in occurrences of all ADRs (n = 1011), severe ADRs (n = 295), drug-drug interactions (n = 312), deaths (n = 87), or intentional overdoses (n = 79), when sex differences in prescription practices were considered. There were no differences in ADR rates among different SSRIs. The most common cause of death among patients taking SSRIs was intentional overdose (n = 65, 74.7%). This was reported in 47 (72.3%) women and 18 (27.7%) men. The most common drugs taken with SSRIs in patients who died of intentional overdoses were benzodiazepines, tricyclic antidepressants (TCAs), narcotics, alcohol, and diphenhydramine. Patients who had severe or fatal ADRs were more likely to be taking an SSRI with 2 or more other drugs, including alcohol. Drug combinations that included another CYP-450 drug were especially problematic. A total of 129 cardiovascular ADRs were reported, most of which were severe. These included rhythm disturbances, blood pressure perturbations, and chest pain or angina. Cardiovascular ADRs most often occurred with concomitant drug use of benzodiazepines, TCAs, histamine H2 antagonists, lithium, and calcium channel blockers. There were 3 deaths from malignant neuroleptic syndrome unassociated with intentional overdose. CONCLUSIONS: SSRIs are relatively safe when their widespread use is compared with the prevalence of ADRs. SSRIs may, however, be associated with ADRs, and even death, following intentional overdose or when taken with 2 or more other drugs or alcohol (particularly another drug metabolized by CYP-450). Physicians prescribing SSRIs need to consider drug-drug interactions and carefully monitor patients with severe affective disorders, comorbid medical conditions (especially cardiovascular disease), alcohol abuse, or a history of overdosing.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it