SARIs work differently from SSRIs. Instead of relying mainly on blocking the serotonin transporter, a SARI like trazodone combines weak serotonin reuptake inhibition with meaningful blockade of the 5-HT2A serotonin receptor, plus antihistamine (H1) and alpha-1 adrenergic blocking activity. That combination is why trazodone tends to be sedating at low doses and is prescribed off-label for sleep far more often than as a primary antidepressant at typical antidepressant doses.
SARI (Serotonin Antagonist and Reuptake Inhibitor)
Also called: Serotonin antagonist/reuptake inhibitor
A class of antidepressant that both blocks certain serotonin receptors (mainly 5-HT2A) and weakly inhibits the reuptake of serotonin. Trazodone is the most widely prescribed drug in this class.