What are the guidelines for diagnosing and managing serotonin syndrome?

From the Guidelines

Serotonin syndrome should be diagnosed and managed promptly by discontinuing the precipitating agent and providing supportive care, including treatment of agitation, hyperthermia, and autonomic instability.

Diagnostic Criteria

The diagnosis of serotonin syndrome can be made using the Hunter criteria, which are the most commonly used criteria 1. The clinical triad of serotonin syndrome consists of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities 1. The modified Dunkley criteria can also be used to diagnose serotonin syndrome, which requires the patient to have taken a serotonergic drug within the last 5 weeks and have any of the following: tremor and hyperreflexia; spontaneous clonus; muscle rigidity, temperature >38°C, and either ocular clonus or inducible clonus; ocular clonus and either agitation or diaphoresis; or inducible clonus and either agitation or diaphoresis 1.

Treatment

Treatment of serotonin syndrome often involves discontinuing the precipitating agent and providing supportive care, including:

• Treatment of agitation with benzodiazepines
• Amelioration of hyperthermia
• Management of autonomic instability with IV fluids and other agents to address abnormal vital signs 1
• In severe cases, emergency sedation, neuromuscular paralysis, and intubation may be considered 1
• Cyproheptadine, a serotonin2A antagonist, may be considered in adult patients, typically starting with 12 mg, followed by 2 mg every 2 hours for continuing symptoms, and a maintenance dose of 8 mg every 6 hours, given orally 1

Key Considerations

• Physical restraints may be detrimental, as they may exacerbate isometric contractions, worsening hyperthermia and lactic acidosis and increasing mortality 1
• Severe cases of serotonin syndrome can be life-threatening, with significant morbidity and mortality associated with the condition 1
• The incidence of and mortality from serotonin syndrome have been increasing due to the growing number and use of proserotonergic medications 1
• A wide variety of medications, including prescription medications, over-the-counter medications, herbal and dietary supplements, and drugs of abuse, have been associated with serotonin syndrome 1

From the Research

Diagnosis of Serotonin Syndrome

• The diagnosis of serotonin syndrome is based on the presence of clinical symptoms, which can include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremors, sweating, and diarrhea 2
• The Hunter Serotonin Toxicity Criteria are used to diagnose serotonin syndrome, which require the presence of one of the following classical features or groups of features: spontaneous clonus; inducible clonus with agitation or diaphoresis; ocular clonus with agitation or diaphoresis; tremor and hyperreflexia; or hypertonia, temperature above 100.4 degrees F (38 degrees C), and ocular or inducible clonus 3
• Serotonin syndrome characteristically presents as the triad of altered mental status, autonomic dysfunction, and neuromuscular excitation 4

Management of Serotonin Syndrome

• The management of serotonin syndrome typically involves discontinuing the use of the substance that caused the excess serotonin levels and providing supportive care, such as intravenous fluids and electrolytes 2
• In severe cases, benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels 2
• Patients with moderate or severe cases of serotonin syndrome require hospitalization, and critically ill patients may require neuromuscular paralysis, sedation, and intubation 3
• The mainstay of treatment for serotonin syndrome is to discontinue the offending drug, and improvement is seen in most patients within 24 hours 4

Prevention of Serotonin Syndrome

• Serotonin syndrome can be prevented by being aware of the medications that can cause it, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, stimulants, lithium, opioids, and certain herbal supplements 2
• Regular information updates and reminders to all those who prescribe medications to patients can help prevent serotonin syndrome 2
• Early clinical recognition and treatment are crucial to prevent significant morbidity 5