Serotonin syndrome: When the happy hormone gets angry

Serotonin syndrome is a life-threatening condition caused by iatrogenic overactivation of 5HT1a and 5HT2a receptors characterized by the triad of encephalopathy, dysautonomia, and neuromuscular abnormalities. Although certain narcotics have been implicated, case reports related to fentanyl are scarce and the entire drug class is likely under-recognized as a potential precipitant in the clinical setting. We describe a postoperative patient who developed moderately severe serotonin syndrome while receiving a high-dose fentanyl infusion in the context of outpatient paroxetine therapy. The case was successfully managed by the withdrawal of the offending agents and treatment with cyproheptadine. We present a summary of the pathophysiology, diagnosis, and management of the serotonin syndrome.