Serotonin Syndrome

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Serotonin Syndrome

Serotonin syndrome is often related to iatrogenic causes - medication interactions and intentional self-poisoning - which develops over the course of hours. The classic triad for recognition we all learn is:

  • Mental Status Changes - anxiety, agitation, restlessness, disorientation

  • Autonomic Hyperactivity - diaphoresis, tachycardia, hypothermia, HTN, diarrhea, vomiting

  • Neuromuscular Abnormalities - tremor, muscle rigidity, myoclonus, hyper-reflexia, b/l babinski (all more pronounced in lower extremities)

Diagnosis is made clinically using Hunter Criteria, patient must be taking one serotonergic agent and meet any ONE of the following:

  • Spontaneous clonus

  • Inducible clonus PLUS agitation or diaphoresis

  • Ocular clonus PLUS agitation or diaphoresis

  • Tremor PLUS hyperreflexia

  • Hypertonia PLUS fever PLUS ocular clonus or inducible clonus

The big question is how do you differentiate the other conditions that make people hot and altered?

  • NMS: Also has hyperthermia, AMS, elevated CK/LFTs, and even muscle rigidity - but - NMS is subacute (days to weeks) instead of acute (hours), is more associated with bradyreflexia, and severe rigidity (buzz word: lead pipe rigidity).

  • Anticholinergic Toxicity: Also has agitation, AMS, hyperthermia - but - take care to go a good MSK exam and note the reflexes and tone which should be normal in the anticholinergic toxidrome

  • Malignant Hyperthermia: Also has rigidity, tachycardia, hyperthermia, and acidosis - but - the clinical situation is different as MH is usually related to halogenated volatile anesthetics and depolarizing muscle relaxers.

Treatment is largely supportive care, but also keep these key steps in mind (they’ll be on boards)

  1. Discontinue offending drugs

  2. Sedate with BZD

  3. If that does not help -> Cyproheptadine

    1. When administered as an antidote for serotonin syndrome, an initial dose of 12 mg is recommended, followed by 2 mg every two hours until clinical response is seen. Cyproheptadine is only available in an oral form! You will likely have to place an NG to administer this medication

Gene Novikov, MD