Risk of Serotonin Syndrome with Concomitant Administration of Linezolid and Serotonin Agonists

Linezolid, an antimicrobial used to treat resistant gram-positive bacteria, can inhibit monoamine oxidase, an enzyme that metabolizes serotonin and other biogenic amines. Inhibition of this enzyme can predispose patients who are concomitantly taking serotonin agonists to serotonin syndrome. Because of the potential of linezolid to inhibit monoamine oxidase, premarketing studies were conducted with drugs such as selective serotonin reuptake inhibitors. No cases of serotonin syndrome were recorded. After linezolid was released to the United States market, several case reports of serotonin syndrome emerged. A literature search revealed 13 cases of serotonin syndrome occurring with the concomitant use of linezolid and drugs possessing serotonergic properties. To direct clinical management of this potential drug interaction, we reviewed reports of serotonin syndrome to determine relevant drug interactions with linezolid and serotonergic drugs and to characterize similarities and differences in the reported cases. Clinicians should obtain complete drug histories to identify patients at risk, strictly monitor drug therapy including concomitant drugs, and receive education about this potential drug interaction and the symptoms of serotonin syndrome.