Anecdotal Failures in the Diagnosis of Serotonin Syndrome


Clinical Question: What is the validity of commonly held beliefs regarding serotonin syndrome (SS)?

Background: SS is a potentially life-threatening condition caused by serotonin excess in the central nervous system. The authors tested the validity of four widely accepted tenets about SS: that the Hunter criteria are superior, that the onset of SS is rapid compared to neuroleptic malignant syndrome (NMS), that hyperthermia is common with SS, and that SS can be distinguished from NMS based on medication history.

Study Design: Systematic review and meta-analysis.

Setting: PubMed and Web of Science.

Synopsis: Researchers identified 299 case reports from 2004 to 2014 in which SS was the most likely diagnosis based on one of three available diagnostic systems. Rhabdomyolysis with creatine kinase >1,500 and ICU treatment were used as proxies for SS severity. The Hunter criteria (the current gold standard) identified fewer overdoses, episodes of rhabdomyolysis, and ICU cases than the Sternbach or Radomski criteria. Combinations of antidepressants with methylene blue, opiates, or linezolid were the most common reasons for ICU admission. Symptom onset was within six hours in only 27.5% of cases. Hyperthermia was present in only 9.2% of patients with SS.

Hospitalists cannot rely on any one set of criteria to diagnose SS. The typical combinations of opiates or linezolid with antidepressants should raise the level of suspicion for SS. Rigidity and rhabdomyolysis occur commonly in both NMS and SS. Hyperthermia and timing of onset are not good indicators to the diagnosis of SS.

Bottom line: A high index of suspicion rather than reliance on classification systems or anecdotal key symptoms is necessary when considering SS.

Citation: Werneke U, Jamshidi F, Taylor DM, Ott M. Conundrums in neurology: diagnosing serotonin syndrome – a meta-analysis of cases. BMC Neurol. 2016;16:97.