OK, so these two have always tripped me up. They are kind of similar, but not really 100% similar. Maybe part of the problem is that they are taught together – you know, kind of like the Monteggiazzi fracture. But then again, a lot of their symptoms overlap. The purpose of this Briefs is to hopefully provide some clarity between the two.

Serotonin syndrome

Serotonin syndrome’s key clinical features are:

  • Hyperthermia
  • Confusion & Agitation
  • Diaphoresis
  • Myoclonus & hyperreflexia
  • Increased muscle tone – especially lower extremities
  • Mydriasis
  • Increases in HR, RR and BP

It occurs in patients who take medications (and substances) with a wide array of psychoactive properties – but classically serotonergic agents. This includes SSRIs, MAOIs, fentanyl, ecstasy (3,4-MDMA), linezolid and tramadol among others. The diagnosis is clinical and the treatment is supportive. The Hunter Toxicity criteria have been proposed for diagnosis. Patients must be taking a serotonergic agent and have ONE of the following:

  • Spontaneous clonus
  • Inducible clonus PLUS agitation or diaphoresis
  • Ocular clonus PLUS agitation or diaphoresis
  • Tremor PLUS hyperreflexia
  • Hypertonia PLUS temperature above 38ºC PLUS ocular clonus or inducible clonus

Serotonin syndrome develops within 24 hours and resolves just as quickly. In addition to supportive measures and withdrawal of the offending drug treatments include benzodiazepines and cyproheptadine.

The most specific finding in serotonin syndrome is myoclonus

Fun fact: Bruxism (teeth grinding) is a classic finding in patients on ecstasy

Neuroleptic malignant syndrome

The key clinical features of NMS are:

  • Hyperthermia
  • Marked muscle rigidity – “lead pipe” rigidity; a stable resistance to passive movement of all joints
  • Hyporeflexia
  • Variable mental status changes from stupor to n normal alertness
  • Normal pupils
  • Increases in HR, RR and BP

NMS is an idiosyncratic medication reaction to dopaminergic agents. It develops over days to weeks. Common offending agents include antipsychotics and similarly neuropharmacologic agents like metoclopramide. Treatment is supportive; dantrolene, bromocriptine, and amantadine are other potential therapies.

The muscle rigidity of NMS is generalized and very severe

How do I know the difference?

Its not easy, especially when patients are on SSRIs and antipsychotics simultaneously. Some differentiating features include:

  • Onset – Serotonin syndrome: 24 hours  /  NMS: days to weeks
  • Neuromuscular symptoms – Serotonin syndrome: Hyperreactivity (tremor, clonus, reflexes)  /  NMS: Bradyreflexia, severe muscular rigidity

Additionally, Per Perry et al. ” the clinical laboratory profile of elevations in creatine kinase, [transaminases], and white blood cell count, coupled with a low serum iron level, distinguishes NMS from SS among patients taking neuroleptic and serotonin agonist medications simultaneously.”

What else is kind of similar and should be on the differential

Acute dystonic reaction, anticholinergic toxicity, malignant hyperthermia, sympathomimetic agents, sedative-hypnotic withdrawal, meningitis, and encephalitis.