Serotonin Syndrome — Emergency

Serotonin syndrome (also called serotonin toxicity) is a potentially life-threatening adverse drug reaction resulting from excessive activity of serotonin in the central and peripheral nervous systems, most often when two or more serotonergic agents are combined or doses are escalated.

Implicated drugs include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, tramadol, linezolid, methylene blue, dextromethorphan, ondansetron, MDMA and herbal supplements such as St John wort.

The clinical triad encompasses mental status changes (anxiety, agitation, delirium), autonomic hyperactivity (tachycardia, hypertension, diaphoresis, hyperthermia, mydriasis) and neuromuscular abnormalities (clonus particularly inducible at the ankles, tremor, hyperreflexia and rigidity).

Diagnosis is clinical (Hunter or Sternbach criteria); exclusion of neuroleptic malignant syndrome, anticholinergic toxicity and malignant hyperthermia is essential. Hyperthermia greater than 41 degrees, severe muscle rigidity and rhabdomyolysis define life-threatening disease.

Treatment requires immediate cessation of all serotonergic agents, aggressive cooling, benzodiazepines for agitation and tremor, intravenous fluids, and cyproheptadine (a serotonin antagonist) in moderate to severe cases; intensive care monitoring and intubation with paralytics may be needed.