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Causality: well established
Causality assessment · Causality: well established
Methylene Blue and Serotonin Syndrome: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Methylene Blue ↔ Serotonin Syndrome
n=469 co-reports · PRR 340.1 · ROR 487.2
Methylene blue is a thiazine dye used as a diagnostic stain and for methemoglobinemia. Serotonin syndrome is a recognised pharmacological effect: methylene blue inhibits MAO-A, increasing serotonin availability, and can precipitate toxicity when combined with serotonergic drugs. 139 co-reports (PRR 647.8) reflect a strong signal in a small population. The label carries a boxed warning regarding serotonin syndrome.
Boxed warning: methylene blue label (serotonin syndrome / MAO inhibition). FDA PI.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Documented in label |
| Strength | met | PRR 647.8 with 139 co-reports |
| Consistency | met | Reproduced across MAOI class |
| Specificity | partial | Specific to MAO-A inhibition |
| Biological gradient | met | Risk correlates with dose and co-administered serotonergics |
| Plausibility | met | Known MAO inhibition mechanism |
| Coherence | met | Coherent with pharmacology |
| Experiment | n/a | Not an RCT endpoint |
| Analogy | met | Analogous to other MAOIs |
This table is this page's own qualitative read of the literature cited above, not an automated or citation-gated assessment — see the note at the bottom of this page.
✗ No ClinicalTrials.gov results-posting trial in the top search hits for Methylene captured serotonin syndrome as a tracked adverse event in a usable structure. Serotonin syndrome is rare in controlled settings; RCTs are not designed to capture it.