Abnormal Eye Movement and Agitated Delirium in a 26-Year-Old

Caroline Tschibelu, MD


January 20, 2021


Serotonin syndrome is a potentially life-threatening condition that occurs secondary to serotonin toxicity in the central and peripheral nervous systems. This can be due to a combination of serotonergic agents, an increase in therapeutic dosing of a serotonergic agent, and an overdose or inadvertent interactions of serotonergic agents. Serotonin syndrome is a clinical diagnosis; therefore, a careful and thorough history and physical and neurologic examinations are essential, as is a high level of suspicion.[1]

Serotonin syndrome results from excessive stimulation, or agonist activity at postsynaptic serotonin receptors; most often implicated is excessive binding at 5-HT2A and 5-HT1A receptors subtypes. Those two subtypes may be the predominant cause of symptoms.[2] Presenting symptoms can widely vary and range from mild to life-threatening.

Serotonin (5-HT) is produced in the neurons from L-tryptophan, and its concentration is regulated through feedback loops controlling its reuptake and metabolism. 5-HT receptors in the central nervous system regulate attention, behavior, temperature, the sleep/wake cycle, appetite, and muscle tone.[3]

5-HT receptors are also located in the peripheral nervous system; peripheral serotonin is produced by intestinal enterochromaffin cells and is involved in the regulation of gastrointestinal motility, uterine contraction, bronchoconstriction, and vascular tone. In addition, 5-HT in platelets promotes their aggregation.

No specific laboratory test is indicated to diagnose serotonin syndrome, and serotonin levels do not correlate with the severity of symptoms. The Hunter criteria are the most accurate diagnostic set available to diagnose serotonin syndrome, with 84% sensitivity and 97% specificity. The criteria require that a patient be taking a serotonergic agent and meet at least one of the following conditions[4]:

  • Spontaneous clonus

  • Inducible clonus with agitation or diaphoresis

  • Ocular clonus with agitation or diaphoresis

  • Tremor and hyperreflexia

  • Hypertonia, temperature > 100.4°F (38°C), and ocular or inducible clonus


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