Serotonin syndrome

General information

  • Increasing incidence mirrors increased use of serotonergic medication
  • May occur in any age
  • Presentation may be very similar to neuroleptic malignant syndrome from which myoclonus and tremor may be the most reliable differentiating signs
  • Usually develops within 6-8 hours from initiating or increasing the dose of serotonergic medication while NMS usually develops over several days
  • Usually resolves within less than 24 hours while NMS typically requires several days
  • Leukocytosis, elevated creatine phosphokinase, elevated hepatic transaminases, and metabolic acidosis are seen in severe cases of both conditions
  • Symptoms and signs include:
    • Hyperreflexia
    • Tremor
    • Myoclonus (inducible or spontaneous)
    • Ocular clonus
    • Muscle rigidity
    • Diaphoresis
    • Agitation
    • Mental status changes
    • Akathisia
    • Mydriasis
    • Incoordination
    • Shivering
    • Dry mucous membranes
    • Babinski sign
    • Increased intestinal motility and diarrhea

Hunter serotonin toxicity criteria

The patient must have taken a serotonergic drug in the past 5 weeks and have at least one of the following criteria:

  • Spontaneous myoclonus
  • Inducible clonus and either agitation or diaphoresis
  • Ocular clonus and agitation or diaphoresis
  • Tremor and hyperreflexia
  • Is hypertonic and has a temperature >38°C and has ocular clonus or inducible clonus

Differential

  • Neuroleptic malignant syndrome
  • Anticholinergic toxicity
  • Malignant hyperthermia

Workup

Depending on the patient’s condition and the differentials being contemplated, the following may be required:

  • Complete blood count
  • Electrolyte status
  • BUN and creatinine
  • CPK
  • Hepatic transaminases
  • Urinalysis
  • Blood and urine cultures
  • CSF analysis and cultures
  • Chest X-ray
  • Head CT

Management

Management is mostly supportive. Early recognition is important.

  • Discontinuation of all serotonergic agents
  • Severely ill patients should be admitted to ICU
  • Autonomic instability may be difficult to manage in severe cases. Prefer short-acting agents and avoid rapid changes in blood pressure and pulse, eg use esmolol or nitroprusside instead of propranolol in hypertensive, tachychardic patients
  • Sedate with benzodiazepines
  • Hydrate
  • Maintain euthermia by antipyretics and passive cooling. If extreme hyperpyrexia consider neuromuscular paralysis and intubation
  • Propranolol, diphenhydramine, chlorpromazine, diazepam, and methysergide have been used to treat serotonin syndrome.
  • Cyproheptadine is a 5-HT2A antagonist and antihistamine that can reverse clinical symptoms in hours. Starting dose is 12 mg, followed by 2 mg every 2 hours until resolution.

Drugs associated with serotonin syndrome

  • 3,4 Methylenedioxymethamphetamine (MDMA or ecstasy)
  • Amphetamines
  • Atypical neuroleptics
  • Buspirone hydrochloride
  • Cocaine
  • Dextromethorphan
  • Dietary supplements: ginseng, St. John’s wort
  • Linezolid
  • Lithium
  • L-tryptophan
  • Lysergic acid diethylamide (LSD)
  • Monoamine oxidase inhibitors
  • Opiates (except morphine)
  • Selective serotonin reuptake inhibitors
  • Serotonin-norepinephrine reuptake inhibitors
  • Tramadol
  • Tricyclic antidepressants
  • Triptans