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Jimmy O. Ibikunle, M.D., Penn State College of Medicine, Department of Psychiatry, 500 University Drive, Hershey, PA 17033

1. Recognize constellation of signs and symptoms for diagnosis of serotonin syndrome.
2. Demonstrate understanding of pharmacokinetics pertinent in medication management
with serotonergic agents.

Serotonin syndrome is a toxic, potentially fatal hyperserotonergic state.(1) It has been reported at initiation, in overdose and combination of serotonergic agents. It also occurs in recreational substance abuse Sternbach’s diagnostic criteria(1) include autonomic, neuromuscular and cognitive symptoms and signs. Method: A retrospective chart review of toxicology consults at a university medical center for reported or suspected overdose and drug interactions involving at least one known serotonergic agent(2) was done. Individuals with substance intoxication and animal bites were excluded. Results: Of the 173 cases, over a 5-year period, 5 met criteria(1) for serotonin syndrome, constituting 2.89%. Mean age was 34.4. Four patients were female. One required ICU stay; others were discharged within 24 hours; all survived. Three cases occurred in the course of medication adjustments: switching from fluoxetine to trazodone, augmenting fluoxetine with Lithium and simultaneously increasing doses of fluoxetine and trazodone. Two cases involved intentional overdose: one with venlafaxine and the other with sertraline; the latter followed a recent switch to fluvoxamine. Cognitive symptoms were the most common initial presentation. Conclusion: Occurrence during medication changes supports an iatrogenic etiology. No cases involved a MAOI, notorious for its precipitant effect, and fluoxetine’s pharmacokinetics(2) suggests its predisposition.


Sternbach H. The serotonin syndrome. American Journal of Psychiatry, 1991;148:705-13.

Mills KC. Serotonin syndrome. American Family Physician, 1995;25:1475-82.

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