Serotonin reuptake inhibitors (SRIs)

Name: Sulfonamide-derived drugs (non-antibacterial)
Creator: Jason Cafer, MD

Every drug whose SERT blockade is clinically significant (serotonicity rating ≥2), whatever its label class: SSRIs, SNRIs, clomipramine, vilazodone, vortioxetine — and the opioids tramadol, meperidine and methadone
Membership is derived from the card’s serotonicity rating, so this row and the drug card cannot disagree
The core antidepressant and anti-anxiety mechanism; benefit builds over weeks as receptors adapt
The non-antidepressant members matter for one reason: they count toward serotonin toxicity with an MAOI
Serotonin toxicity with MAOIs (potentially fatal), bleeding with NSAIDs and anticoagulants, hyponatremia in the elderly, sexual dysfunction, discontinuation symptoms
Washout before an MAOI is drug-specific — fluoxetine’s long half-life is the classic trap

Class at a glance

Every drug whose SERT blockade is clinically significant (serotonicity rating ≥2), whatever its label class: SSRIs, SNRIs, clomipramine, vilazodone, vortioxetine — and the opioids tramadol, meperidine and methadone
Membership is derived from the card’s serotonicity rating, so this row and the drug card cannot disagree

The core antidepressant and anti-anxiety mechanism; benefit builds over weeks as receptors adapt
The non-antidepressant members matter for one reason: they count toward serotonin toxicity with an MAOI

Serotonin toxicity with MAOIs (potentially fatal), bleeding with NSAIDs and anticoagulants, hyponatremia in the elderly, sexual dysfunction, discontinuation symptoms
Washout before an MAOI is drug-specific — fluoxetine’s long half-life is the classic trap

Why are tramadol and meperidine in a serotonin reuptake inhibitor row?
Their SERT blockade is clinically significant — enough to cause serotonin toxicity with an MAOI — even though they are prescribed as opioids.