Sixty percent of patients with serotonin syndrome present within 6 hours of medication initiation, overdose, withdrawal, or change in dosage and 74% present within 24 hours.13 As excess serotonin

levels can present with a spectrum of toxicity from mild cases in which medication(s) can be continued with close observation, to severe and life-threatening cases requiring cessation of the medication(s), depending upon the intrasynaptic concentration, some authors prefer the term “serotonin toxicity” to serotonin syndrome.14 The diagnosis of serotonin syndrome is based upon the history of medication use, the physical examination, and exclusion of other neurological disorders such as meningoencephalitis, delirium tremens, heat stroke, neuroleptic malignant syndrome, malignant hyperthermia, and poisoning from anticholinergic drugs Cilomilast price (summarized in Table 2). The diagnosis is suggested with a sensitivity of 84% and specificity of 97% (as compared to the gold standard of diagnosis by a medical toxicologist in patients who overdosed on a serotonergic

drug) by the Hunter Serotonin Toxicity Criteria (Box 1).14 ACP-196 manufacturer In the presence of a serotonergic agent and one of the following symptoms: Spontaneous clonus The Hunter criteria have not been validated in patients who develop serotonin toxicity on therapeutic doses of serotonergic agents (either single agents or as a drug interaction). Other diagnostic criteria have

been proposed that might better detect the full range of mild to severe cases, but are not completely validated.15,16 A second validated set of diagnostic criteria is the Sternbach Criteria (Box 2).17 1 Recent addition or increase in a known serotonergic agent Following an overdose of a serotonergic drug, the Sternbach Criteria suggest a serotonin syndrome diagnosis with a sensitivity of 75% and a specificity of 96%.14 Despite these validated criteria, serotonin syndrome often remains underdiagnosed – perhaps because of its variable clinical manifestations and a general lack of awareness of the syndrome among Cyclooxygenase (COX) clinicians. Management of serotonin toxicity varies depending upon the severity of symptoms. Standard approaches may include18: Remove or modify responsible medications With appropriate management, symptoms resolve within 24 hours for about 60% of patients, but drugs with long durations of action or active metabolites may cause prolonged symptoms.9 There is discussion regarding the exact transition point between tolerable side effects of serotonergic administration and a toxic serotonin syndrome requiring withdrawal of medication. Some patients with stable mild subacute or chronic symptoms fulfilling criteria for serotonin syndrome (such as mild tremor and hyperreflexia) might safely continue the medication with close observation.