What are the diagnostic criteria for Serotonin syndrome?

The Bottom Line:

Hunter Serotonin Toxicity Criteria: Decision Rules
In the presence of a serotonergic agent:
1. IF (spontaneous clonus ¼ yes) THEN serotonin toxicity ¼ YES
2. ELSE IF (inducible clonus ¼ yes) AND [(agitation ¼ yes) OR (diaphoresis ¼ yes)]
THEN serotonin toxicity ¼ YES
3. ELSE IF (ocular clonus ¼ yes) AND [(agitation ¼ yes) OR (diaphoresis ¼ yes)] THEN
serotonin toxicity ¼ YES
4. ELSE IF (tremor ¼ yes) AND (hyperreflexia ¼ yes) THEN serotonin toxicity ¼ YES
5. ELSE IF (hypertonic ¼ yes) AND (temperature > 38 C) AND [(ocular clonus ¼ yes)
OR (inducible clonus ¼ yes)] then serotonin toxicity ¼ YES
6. ELSE serotonin toxicity ¼ NO

Reference: Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM.  The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003 Sep;96(9):635-42. 



A ‘yes’ decision on any of the decision rules indicates definite or significant serotonin toxicity of sufficient clinical significance to require consideration of treatment with specific 5-HT2A antagonists. Such patients require admission and observation for signs of worsening serotonin toxicity. We also found that the presence of a temperature  38.5C
and/or marked hypertonia or rigidity (particularly truncal) indicated severe serotonin toxicity with a high risk of progression to respiratory compromise, requiring urgent active intervention. This included active measures to reduce fever as well as consideration of elective neuromuscular paralysis, endotracheal intubation and assisted ventilation. In
this context, the presence of a rising pCO2 indicated a medical emergency requiring urgent respiratory support.

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