CYP2D6 and serotonin syndrome: CYP2D6 poor metabolizers and those with deficient serotonin (5-HT) uptake who take tramadol may be at risk for serotonin syndrome (SS), which begins within 24 hours of starting or increasing a 5-HT reuptake or CYP2D6 inhibitor (Beakley, Kaye, & Kaye, 2015; Houlihan, 2004; Leppert, 2009).