The diagnosis is likely if patients have taken a serotonergic drug and have muscle hypertonia; spontaneous clonus; tremor plus hyperreflexia; or the combination of ocular or inducible clonus; plus either agitation, diaphoresis, or temperature > 38° C Serotonin syndrome can often be differentiated from neuroleptic malignant syndrome by use of serotonergic drugs, rapid onset (eg, within 24 hours of its drug trigger), and hyperreflexia.