Clinical presentation of serotonergic toxidrome

Serotonergic toxidrome is best described as a spectrum of severity.

Effects of mild serotonergic toxidrome include tremor, mild tachycardia, inducible clonus, and lower limb hyperreflexia. It is unlikely to trouble the patient and often occurs at therapeutic doses of serotonergic drugs.

Effects of moderate serotonergic toxidrome include agitation, sustained clonus, tachycardia and hyperthermia less than 39ºC. It causes the patient distress and requires symptomatic relief.

Severe serotonergic toxidrome (serotonergic crisis) is a medical emergency and progresses to life-threatening multiorgan failure if not treated within hours. Effects of severe serotonergic toxidrome include rapidly progressive hyperthermia, muscle rigidity with sustained clonus, and seizures. It most commonly occurs with co-ingestion of serotonergic drugs that cause serotonin excess through different pharmacological actions. A monoamine oxidase inhibitor or stimulant drug is often involved in the most severe cases.

Note: Severe serotonergic toxidrome is a medical emergency and progresses to life-threatening multiorgan failure if not treated promptly.
The Hunter serotonin toxicity criteria (see Hunter serotonin toxicity criteria) can be used to help confirm a diagnosis of moderate or severe serotonergic toxidrome.

Several rare but serious conditions can symptomatically mimic serotonergic toxidrome (ie fever, altered conscious state, neuromuscular symptoms). Conditions to exclude are:

  • withdrawal syndromes—alcohol, baclofen, benzodiazepines, gamma-hydroxybutyrate
  • CNS infection—encephalitis, meningitis
  • nonconvulsive seizures
  • malignant hyperthermia.

Other toxidromes, such as anticholinergic toxidrome, sympathomimetic toxidrome and neuroleptic malignant syndrome, can also be confused with serotonergic toxidrome.

Figure 1. Hunter serotonin toxicity criteria.

[NB1]

A clinical diagnosis of serotonergic toxidrome can be made if the patient has taken a serotonergic drug and meets one of the following criteria:

  • spontaneous clonus
  • inducible clonus PLUS EITHER agitation or sweating
  • ocular clonus PLUS EITHER agitation or sweating
  • tremor PLUS hyperreflexia
  • hypertonia PLUS temperature more than 38ºC PLUS EITHER inducible clonus or ocular clonus.
Note:

NB1: These criteria have an 84% sensitivity and 97% specificity for diagnosis of serotonergic toxidrome.

Adapted with permission of Oxford University Press from: Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635-42. [URL]