CYP2D6 and serotonin syndrome: Combination of tramadol with selective serotonin reuptake inhibitors (SSRIs; fluoxetine, paroxetine, and to a lesser extent sertraline) inhibits CYP2D6 and may cause the serotonin syndrome because SSRIs, apart from inhibiting tramadol metabolism, increase the level of serotonin in the CNS; they should not be coadministered with tramadol.