What are the signs, symptoms, and treatment of serotonin syndrome?

From the Guidelines

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin in the nervous system, and its treatment requires immediate discontinuation of all serotonergic medications and supportive care, with the administration of benzodiazepines and cyproheptadine in moderate to severe cases. The classic triad of symptoms includes altered mental status (confusion, agitation, hallucinations), autonomic instability (high fever, sweating, rapid heart rate, high blood pressure, dilated pupils), and neuromuscular abnormalities (tremor, muscle rigidity, hyperreflexia, clonus) 1. Additional symptoms may include shivering, diarrhea, headache, and in severe cases, seizures or loss of consciousness.

Signs and Symptoms

The signs and symptoms of serotonin syndrome can vary in severity and may include:

• Altered mental status: confusion, agitation, hallucinations
• Autonomic instability: high fever, sweating, rapid heart rate, high blood pressure, dilated pupils
• Neuromuscular abnormalities: tremor, muscle rigidity, hyperreflexia, clonus
• Shivering, diarrhea, headache
• Seizures or loss of consciousness in severe cases

Treatment

Treatment of serotonin syndrome requires immediate discontinuation of all serotonergic medications and supportive care. For mild cases, observation and symptom management may be sufficient. Moderate to severe cases require hospitalization, with benzodiazepines like lorazepam (0.5-2mg IV) used to control agitation and tremor. Cyproheptadine, a serotonin antagonist, is administered at 12mg initially followed by 2mg every 2 hours until symptoms improve, then 8mg every 6 hours (maximum 32mg daily) 1. Severe hyperthermia requires aggressive cooling measures, and muscle rigidity may need treatment with paralytic agents in intensive care.

Prevention

Serotonin syndrome typically develops within hours of starting or increasing a serotonergic medication, or when combining medications that increase serotonin levels such as SSRIs, SNRIs, MAOIs, triptans, certain antibiotics, or illicit drugs like MDMA 1. Most cases resolve within 24-72 hours with proper treatment, but without intervention, it can progress rapidly to multi-organ failure and death. Therefore, it is essential to be cautious when prescribing serotonergic medications and to monitor patients closely for signs and symptoms of serotonin syndrome.

From the Research

Signs and Symptoms of Serotonin Syndrome

• Alteration of mental status, such as agitation, confusion, and rapid heart rate 2, 3
• Abnormalities of neuromuscular tone, including muscle rigidity, tremors, and hyperreflexia 2, 4
• Autonomic hyperactivity, characterized by high blood pressure, dilated pupils, sweating, and diarrhea 2, 3
• Other common clinical features include clonus, tachycardia, increased bowel sound, diaphoresis, fever, hypertension, and myoclonus 4

Treatment of Serotonin Syndrome

• Discontinuation of the offending serotonergic agent(s) 2, 3
• Supportive care, such as intravenous fluids and electrolytes, to manage hyperthermia and autonomic dysfunction 2, 3
• Administration of serotonin antagonists, such as cyproheptadine, to reduce serotonin levels 2, 3, 4, 5
• Use of benzodiazepines to control agitation and muscle rigidity in severe cases 3

Management and Prevention

• Prompt recognition and supportive care are crucial in managing serotonin syndrome, especially in mild cases 2
• Patients with moderate and severe cases require inpatient hospitalization and close monitoring 2
• Regular updates and reminders for physicians on the condition and associated drugs can help prevent misdiagnosis and improve management 3
• Inhibition of tryptophan hydroxylase (TPH) may provide an opportunity to pharmacologically target central 5-HT synthesis and develop new treatments for severe serotonin syndrome 6