From the Guidelines
Serotonin syndrome is a life-threatening condition that requires immediate discontinuation of serotonergic medications and supportive care, with severe cases necessitating administration of serotonin antagonists like cyproheptadine and aggressive cooling measures. The signs and symptoms of serotonin syndrome typically develop within hours of taking medications that increase serotonin and include a triad of cognitive-behavioral changes, autonomic hyperactivity, and neuromuscular abnormalities 1. Cognitive symptoms include agitation, confusion, hallucinations, and anxiety, while autonomic signs include hyperthermia (often >38°C), tachycardia, hypertension, dilated pupils, sweating, flushing, and diarrhea. Neuromuscular manifestations include tremor, muscle rigidity, hyperreflexia, clonus (particularly in the lower extremities), and myoclonus. In severe cases, seizures, rhabdomyolysis, metabolic acidosis, renal failure, and death can occur 1.
The syndrome results from medications that increase serotonin levels, particularly when combining multiple serotonergic drugs such as SSRIs, SNRIs, MAOIs, triptans, certain opioids (tramadol, meperidine), and some over-the-counter products containing dextromethorphan or St. John's Wort. Treatment involves immediately discontinuing all serotonergic medications, providing supportive care, and in moderate to severe cases, administering serotonin antagonists like cyproheptadine, with a typical dosage of 12 to 24 mg over 24 hours 1. Benzodiazepines may be used for agitation and muscle rigidity, while severe hyperthermia requires aggressive cooling measures. Some key points to consider in the management of serotonin syndrome include:
- Discontinuing the precipitating agent and providing supportive care
- Administering serotonin antagonists like cyproheptadine in moderate to severe cases
- Using benzodiazepines for agitation and muscle rigidity
- Implementing aggressive cooling measures for severe hyperthermia
- Considering consultation with a toxicologist or poison control center for guidance on management 1.
It is essential to note that patients with serotonin syndrome can deteriorate rapidly, and close observation and preparation for rapid intervention are crucial. In milder cases, evaluation, observation, and discharge with close, additional outpatient management may be considered 1.
From the Research
Signs of Serotonin Syndrome
- Alteration of mental status, such as agitation, confusion, and rapid heart rate 2, 3
- Abnormalities of neuromuscular tone, including muscle rigidity and tremors 2, 3
- Autonomic hyperactivity, characterized by high blood pressure, dilated pupils, sweating, and diarrhea 2, 3
- Hyperthermia, although not always present 4
- Neuromuscular abnormalities, such as muscle rigidity and tremors 5
Effects of Serotonin Syndrome
- Can range in severity from mild to life-threatening 2, 3
- May lead to seizures, shock, and death if not recognized and treated early 4
- Can cause cardiovascular complications, including extreme changes in blood pressure 6
- May require inpatient hospitalization, especially in moderate and severe cases 2
Management of Serotonin Syndrome
- Discontinuation of the offending agent(s) 2, 3
- Aggressive supportive care to treat hyperthermia and autonomic dysfunction 2
- Administration of serotonin antagonists, such as cyproheptadine or chlorpromazine 2, 3
- Use of benzodiazepines to control agitation and muscle rigidity 3, 6
- Potential use of propofol or higher doses of cyproheptadine in severe cases 6