Serotonin Syndrome (Serotonin Toxicity)

Develops within hours of starting a serotonergic drug, increasing its dose, or combining interacting agents. The key distinguishing feature is neuromuscular excitation (clonus — including ocular clonus — and myoclonus), which is not typically seen in other toxidromes.

Clinical triad

• Neuromuscular excitation — hyper-reflexia, clonus, shivering, tremor, hypertonia, rigidity
• Autonomic effects — hyperthermia (mild <38.5°C, severe >38.5°C), diaphoresis, flushing, mydriasis, tachycardia
• CNS effects — agitation, anxiety, confusion

Severity spectrum

Severity	Features
Mild	Unlikely to interfere with the patient; can occur even at therapeutic doses
Moderate	Symptoms cause the patient distress
Severe (serotonin crisis)	Rapidly progressive hyperthermia and muscle rigidity — a medical emergency, can progress to multiorgan failure within hours if untreated. Usually involves serotonergic drugs acting at different sites (e.g. an MAOI plus an SSRI).

Implicated medications

SSRIs, SNRIs, TCAs, MAOIs; opioids (especially tramadol, also pethidine, fentanyl, dextromethorphan); St John’s Wort; amphetamines; MDMA/ecstasy. Notably not typically implicated: triptans, ondansetron.

Treatment

• Cease the inciting agent(s) in all cases.
• Mild–moderate toxicity generally needs no active treatment beyond stopping the drug.
• Severe cases need hospitalisation with sedation, intubation and active cooling as required.