Serotonin syndrome

Epidemiology

Etiology

Serotonergic drugs

Antidepressants (e.g., MAOIs, SSRIs, SNRIs, tricyclic antidepressants, vortioxetine, vilazodone, trazodone)
Anxiolytics (e.g., buspirone)
Anticonvulsants (e.g., valproate)
Opioids (e.g., tramadol, meperidine)
NMDA receptor antagonists (e.g., dextromethorphan)
5-HT3 receptor antagonists (e.g., ondansetron)
Serotonin receptor agonists (e.g., triptans, ritonavir)
Antibiotics (e.g., linezolid)
Herbal supplements (e.g., St. John's wort, ginseng, tryptophan)
- Tryptophan is precursor of serotonin
Recreational stimulants (e.g., MDMA, cocaine)

Tip

Serotonin syndrome rarely occurs with a single serotonergic drug used at therapeutic doses. More commonly, it is due to the combined effects of several serotonergic medications, overdose, and/or a drug-drug interaction. E.g. a depressed patient also takes linezolid.

Pathophysiology

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Clinical features

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Onset: acute, typically within 24 hours of administration of the causative drug
Classic triad
- Autonomic dysfunction
  - Diaphoresis
  - Tachycardia
  - Hypertension
  - Mydriasis
- Neuromuscular excitability: can lead to hyperthermia
  - Contrast to Parkinson disease
  - Hyperreflexia
  - Myoclonus
  - Clonus
  - Horizontal ocular clonus
  - Hypertonicity
  - Rigidity (especially in the lower extremities)
- Altered mental status
  - Delirium
  - Psychomotor agitation

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Diagnostics

Treatment

Agitation and excessive muscle activity: Treat with benzodiazepines.
Hyperthermia: Initiate cooling measures, e.g., by reducing ambient temperature, applying cooling blankets or ice packs, administering cold IV fluids.
Autonomic instability
- Give antihypertensive treatment.
- Treat MAOI-induced hypotension or shock.
Moderate to severe and/or refractory cases
- Consider treatment with 5-HT2A receptor antagonists: cyproheptadine