Excess
serotonin in the central nervous system leads to a condition commonly referred to as the
serotonin syndrome, but better described as a spectrum of toxicity -
serotonin toxicity.
Serotonin toxicity is characterised by neuromuscular excitation (clonus,
hyperreflexia,
myoclonus, rigidity), autonomic stimulation (
hyperthermia,
tachycardia, diaphoresis,
tremor,
flushing) and changed mental state (anxiety, agitation,
confusion).
Serotonin toxicity can be: mild (serotonergic features that may or may not concern the patient); moderate (toxicity which causes significant distress and deserves treatment, but is not life-threatening); or severe (a medical emergency characterised by rapid onset of severe
hyperthermia,
muscle rigidity and
multiple organ failure). Diagnosis of
serotonin toxicity is often made on the basis of the presence of at least three of Sternbach'
s 10 clinical features. However, these features have very low specificity. The Hunter
Serotonin Toxicity Criteria use a smaller, more specific set of clinical features for diagnosis, including clonus, which has been found to be more specific to
serotonin toxicity. There are several
drug mechanisms that cause excess
serotonin, but severe
serotonin toxicity only occurs with combinations of drugs acting at different sites, most commonly including a
monoamine oxidase inhibitor and a
serotonin reuptake inhibitor. Less severe toxicity occurs with other combinations, overdoses and even single-
drug therapy in susceptible individuals. Treatment should focus on cessation of the serotonergic medication and supportive care. Some
antiserotonergic agents have been used in clinical practice, but the preferred agent, dose and indications are not well defined.