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Causality: well established
Causality assessment · Causality: well established
Tramadol 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.
Tramadol ↔ Serotonin syndrome
n=624 co-reports · PRR 18.9 · ROR 19.2
Tramadol is a weak mu-opioid agonist that also inhibits serotonin and noradrenaline reuptake; excess serotonergic activity can produce serotonin syndrome — agitation, clonus, hyperthermia, and autonomic instability — carried here as 624 co-reports (PRR 18.9). Risk is greatest when tramadol is combined with SSRIs, SNRIs, MAOIs, or other serotonergic drugs, and the label warns of this interaction.
Regulatory basis: tramadol prescribing information — serotonin-syndrome interaction warning with serotonergic drugs.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Onset within hours to days |
| Strength | met | PRR 18.9, large |
| Consistency | met | Reproduced across case series |
| Specificity | met | Fairly specific to serotonergic drugs |
| Biological gradient | met | Worse with higher doses |
| Plausibility | met | Excess synaptic serotonin |
| Coherence | met | Fits the mechanism |
| Experiment | n/a | Not a trial endpoint |
| Analogy | met | Analogous to other serotonergic drugs |
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 tramadol captured serotonin syndrome as a tracked adverse event in a usable structure. Serotonin syndrome is an interaction-driven event and is not captured as a coded adverse event in analgesic trials.