Savvy Psychopharmacology

Serotonin syndrome: How to keep your patients safe

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A nonspecific presentation

Unfortunately, many of the symptoms of serotonin syndrome are nonspecific, and the severity varies among patients.2,3 The onset of symptoms usually occurs within 6 to 8 hours after ingestion of a serotonergic agent.5 It is important to immediately recognize the symptoms (Table 22-5) and formulate a differential diagnosis because sudden progression of symptoms is common and may lead to life-threatening circumstances.1,3

Clinical presentation of serotonin syndrome

In mild cases of serotonin syndrome, patients may have a low-grade fever or be afebrile. Hyperthermia tends to be present in moderate and severe cases, with temperatures >41°C (105.8°F) during life-threatening cases. Diaphoresis and tachycardia may be present regardless of severity. Additional autonomic irregularities include hypertension, tachypnea, nausea, vomiting, diarrhea, and hyperactive bowel sounds. In terms of neuromuscular abnormalities, hyperreflexia is a primary concern, as well as myoclonus. As the severity progresses to life-threatening, the clonus may convert from inducible to spontaneous and slow, continuous lateral eye movements may be present. Additional neuromuscular symptoms include tremor, akathisia, and muscle rigidity.1,3-5

Common mental status changes during mild cases include restlessness and anxiety. Abnormal mentation during moderate cases may present as increased hypervigilance and agitation, and this may advance to delirium or coma in severe cases. As the severity intensifies, the risk of developing additional physiological complications also increases. Rhabdomyolysis may occur due to muscle damage and myoglobinuria secondary to hyperreflexia, myoclonus, hypertonicity, and muscle rigidity. Muscle breakdown may then progress to further complications, such as renal failure. In rare instances, serotonin syndrome can result in seizures or death.1,3-5

Medication history tips off the diagnosis

The first step in diagnosing serotonin syndrome is to conduct a thorough review of the patient’s medication history, specifically taking into account any recent exposure to serotonergic agents.3,5 It is important to ask about prescription medications as well as over-the-counter products, herbal supplements, and illicit substances.1,4 When reviewing the medication history, investigate whether there may have been a recent change in therapy with serotonergic agents. Also, determine when the patient’s symptoms began in relation to exposure to serotonergic agents.4

Hunter Serotonin Toxicity Criteria

After the medication review, conduct a thorough physical and neurologic examination to identify current symptoms and severity.1,3 No specific laboratory test is available to definitively confirm the diagnosis of serotonin syndrome.1,4 Monitoring of serum serotonin is not recommended because the levels do not correlate with symptom severity.3 The recommended diagnostic tool is the Hunter Serotonin Toxicity Criteria (Figure1,3).3,4 Historically, the Sternbach’s Diagnostic Criteria for serotonin syndrome were used for diagnosis; however, the Hunter Serotonin Toxicity Criteria are more sensitive (96% vs 75%) and more specific (97% vs 84%) than the Sternbach’s Diagnostic Criteria for serotonin syndrome.1,3-5

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