Moderate
Probable
Description
Sertraline combined with trazodone may increase the risk of serotonin syndrome due to additive serotonergic effects.
Mechanism
Sertraline inhibits SERT; trazodone inhibits serotonin reuptake and is a 5-HT2 receptor antagonist, producing combined serotonergic stimulation.
Clinical Significance
Case reports of serotonin syndrome exist; the combination is sometimes used for treatment-resistant depression with insomnia under close monitoring.
Management
Use at the lowest effective doses; monitor for signs of serotonin toxicity including agitation, tremor, and hyperthermia.