Association of Linezolid With Risk of Serotonin Syndrome in Patients Receiving Antidepressants
Bibliographic record
Abstract
Importance: Linezolid has the potential to interact with some antidepressants, leading to serotonin syndrome. However, few empirical data support warnings for patients taking antidepressants to avoid linezolid. Objectives: To examine the incidence of serotonin syndrome in patients receiving oral linezolid and how concomitant antidepressant treatment changes this risk. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative databases at ICES to collect data from outpatients 66 years or older in Ontario, Canada, who were prescribed oral linezolid for any duration from October 1, 2014, to January 1, 2021, with follow-up to 30 days (January 31, 2021). Exposures: The use of antidepressants while receiving linezolid therapy vs no antidepressant use while receiving linezolid therapy. Main Outcomes and Measures: The primary outcome was clinically significant serotonin syndrome based on a physician diagnosis, Sternbach criteria, or the Hunter Serotonin Toxicity Criteria within 30 days of starting oral linezolid treatment. Secondary outcomes were altered mental status, hospitalization, or death within 30 days of starting linezolid treatment. Results: The study included 1134 patients (age ranges, 66-69 years for 225 patients [19.8%], 70-79 years for 473 patients [41.7%], and ≥80 years for 436 patients [38.4%]; 595 [52.5%] male) who were prescribed linezolid. Of 1134 patients, 215 (19.0%) were also taking antidepressants. Serotonin syndrome occurred in fewer than 6 patients (<0.5%). The number of serotonin syndrome cases were fewer in the antidepressant group. In a propensity score-matched cohort, the adjusted risk difference for serotonin syndrome between the antidepressant group and the no antidepressant group was -1.2% (95% CI, -2.9% to 0.5%). There were similar rates of altered mental status, hospitalization, and death between the propensity score-matched groups. Conclusions and Relevance: In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely. Concurrent antidepressants did not significantly increase the risk of serotonin syndrome. These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction.
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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 | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".