Pediatric Selective Serotonin Reuptake Inhibitor Toxicity Differential Diagnoses

Updated: Apr 12, 2022
  • Author: Mohamed K Badawy, MD, FAAP; Chief Editor: Stephen L Thornton, MD  more...
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Diagnostic Considerations

Serotonin syndrome produces a clinical picture that is very similar to neuroleptic malignant syndrome (NMS). Both syndromes are associated with autonomic dysfunction, alteration of mental status, rigidity, and hyperthermia. Clinical differentiation between these syndromes is very important because management may differ. For example, chlorpromazine may be of some benefit in serotonin syndrome, whereas it may cause further deterioration in NMS. Distinctions between the syndromes include the following:

  • NMS develops in association with neuroleptics, whereas serotonin syndrome develops in association with serotonergic agents.
  • NMS has a slow onset (days to weeks) and a slow progression of 24-72 hours, whereas serotonin syndrome has a more rapid onset and progression.
  • NMS is associated with bradykinesia and lead pipe rigidity, whereas serotonin syndrome is associated with hyperkinesia and less rigidity.
  • NMS is an idiosyncratic reaction to therapeutic doses, whereas serotonin syndrome is a manifestation of toxicity, frequently generated from the combination of 2 drugs with serotonergic activity.

A study concluded that although the characteristics of serotonin syndrome are well defined, some physicians may not be aware of the phenomenon. The retrospective review reported that 5 of 7 patients with serotonin syndrome were initially diagnosed with exacerbation of their psychiatric disorder, 2 patients were diagnosed with gastroenteritis, and 1 patient was diagnosed with a severe drug overdose. [11]

Neonatal serotonin toxicity

Neonates born to mothers who took therapeutic SSRI medications during pregnancy may exhibit symptoms due to toxicity or to drug withdrawal, or may be asymptomatic. Why this variation occurs is not fully understood. With symptomatic newborns it is important to differentiate whether they are manifesting toxicity or withdrawal; SSRIs are excreted in breast milk, so breastfeeding can help alleviate withdrawal symptoms but will exacerbate toxicity. Elevated Neonatal Abstinence Syndrome (NAS) scores are an early indication of both toxicity and withdrawal symptoms. Detectable neonatal drug levels and the presence of clonus support the diagnosis of toxicity. [12]   

Differential Diagnoses