TABLE 1532 Clinical Presentation of Serotonin Syndrome

There are no confirmatory laboratory tests for serotonin syndrome. Therefore, the diagnosis of serotonin syndrome is based entirely on clinical suspicion and exclusion of other psychiatric and medical conditions. Serum chemistry tests, drug levels, cerebral spinal fluid analysis, and brain computed tomographic scan results are usually within normal limits. The differential diagnosis for serotonin syndrome is identical to those conditions listed in Chap. 154, "Monoamine Oxidase Inhibitors," Table 154-3.

The initial treatment of serotonin syndrome includes discontinuing all serotonergic drugs and providing appropriate supportive care. All patients with serotonin syndrome should be admitted to the hospital until their symptoms have completely resolved. The more severely ill patients require admission to an intensive care unit. Approximately 25 percent of patients require endotracheal intubation and ventilatory support. Most patients will show dramatic improvement within 24 h after symptom onset. However, fatalities have been reported. There is an estimated 11 percent mortality rate associated with serotonin syndrome.

At present, there are no accepted guidelines for the use of serotonin antagonists in the treatment of serotonin syndrome. Isolated human case reports suggest that cyproheptadine, methysergide, and propranolol have the potential to be effective antiserotonergic agents. Benzodiazepines are nonspecific serotonin antagonists and can be used to decrease patient discomfort and promote muscle relaxation. Cyproheptadine (Periactin) appears to be the most effective antiserotonergic agent in humans.1 ,.!.8 It should be on most hospital formularies. The initial dose is 4 to 8 mg PO. This dose can be repeated in 2 h if no response is noted to the initial dose. Cyproheptadine therapy should be discontinued if no response is noted after 16 mg has been administered. Patients who respond to cyproheptadine are usually given 4 mg every 6 h for 48 h to prevent recurrences. The use of dopamine agonists (e.g., bromocriptine) have no accepted role in managing patients with serotonin syndrome. Dantrolene (0.5 to 2.5 mg/kg IV q6h, maximum 10 mg/kg/24 h or 50 to 100 mg bid PO) is a nonspecific muscle relaxant that is occasionally used in serotonin syndrome, but it should be primarily restricted for the treatment of malignant hyperthermia. Patients with muscle rigidity, seizures, or hyperthermia should be closely monitored for rhabdomyolysis and/or metabolic acidosis. Once a patient recovers from serotonin syndrome, it is best to avoid future exposure to serotonergic drugs (Xable,.,M153:1), although the risk of recurrence is unknown.

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