Causality assessment · Causality: well established

Fluoxetine and Serotonin syndrome: is the FAERS signal real?

n=1,720 co-reports · PRR 31.2 · ROR 32.0

Fluoxetine side-effect profile All assessments See in the full list

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.

Causality: well established

Fluoxetine ↔ Serotonin syndrome

n=1,720 co-reports · PRR 31.2 · ROR 32.0

Fluoxetine, a selective serotonin-reuptake inhibitor, raises synaptic serotonin; excess serotonergic activity produces serotonin syndrome — agitation, clonus, hyperthermia, autonomic instability — most often when an SSRI is combined with another serotonergic drug (MAOIs, tramadol, triptans, linezolid). In this dataset serotonin syndrome carries 1,720 co-reports (PRR 31.2). Fluoxetine's long half-life makes the effect linger after the drug is stopped, and MAOI combinations are contraindicated.

Regulatory basis: fluoxetine prescribing information — serotonin syndrome; contraindicated with MAOIs.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Onset within hours to days of serotonergic load
Strength	met	PRR 31.2, large
Consistency	met	Reproduced across serotonergic drugs
Specificity	partial	Not specific to one drug within the class
Biological gradient	met	Worse with higher combined serotonergic load
Plausibility	met	Excess-serotonin mechanism
Coherence	met	Fits SSRI pharmacology
Experiment	met	Case series and dechallenge support it
Analogy	met	Analogous to other SSRI/MAOI combinations

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 fluoxetine captured serotonin syndrome as a tracked adverse event in a usable structure. Serotonin syndrome is usually combination-triggered and rarely arises in single-agent trial arms, so trials did not capture it as a coded event.