Requested DocAlert: How to Recognize Serotonin Syndrome

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How to Recognize Serotonin Syndrome

Despite inconsistencies among different sets of criteria, some diagnostic indicators are critical.

The serotonin syndrome (SS) can result from overstimulation of 5-HT1A and 5-HT2 receptors, as manifested by neuromuscular hyperexcitability (such as myoclonus, tremor, hyperreflexia). Because SS can occur with commonly used psychiatric drugs (selective serotonin reuptake inhibitors [SSRIs], migraine medications, opiates), it is important for clinicians to recognize it early. Several classification systems for SS (i.e., Sternbach, Radomski, and Hunter) have been published. Now, researchers have conducted a meta-analysis of 299 adult cases in the literature to compare these sets of criteria.

Topics included how SS compared with neuroleptic malignant syndrome (NMS) and whether hyperthermia was a necessary criterion. Much of the information about these systems was derived from few publications or those limited to a narrow patient population (such as only those taking SSRIs, only in overdose, anecdotal data).

Not all patients had rapid onset, and few presented with hyperthermia. SS was difficult to differentiate from NMS in some cases, especially because some medications have both serotonergic and antidopaminergic properties. A definitive conclusion regarding the relative superiority of the three classification systems could not be reached.


For the practitioner, this meta-analysis provides a review of warning symptoms of SS. When medications with serotonergic properties are prescribed and the patient develops signs of hyperexcitability — whether neurological (myoclonus, tremor, rigidity), vegetative (fever, sweating, tachycardia), or mental (agitation, restlessness, confusion) — we need to immediately consider stopping medications and consider whether the patient needs an emergency evaluation.

Jonathan Silver, MD reviewing Werneke U et al. BMC Neurol 2016.


Werneke U et al. Conundrums in neurology: Diagnosing serotonin syndrome – a meta-analysis of cases. BMC Neurol 2016; 16:97.
[Free full-text BMC Neurol article PDF in PubMed® Central | PubMed® abstract]

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