From the Guidelines
Serotonin syndrome is a medical emergency that requires immediate discontinuation of the precipitating agent and supportive care, with a mortality rate of approximately 11% and significant morbidity associated with severe cases. The condition is caused by excessive serotonin levels in the body, typically resulting from medication interactions, and presents with a triad of symptoms: mental status changes, autonomic instability, and neuromuscular abnormalities 1. Common causative agents include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, triptans, certain opioids, and over-the-counter products containing dextromethorphan or St. John's Wort.
Key Symptoms and Treatment
- Mental status changes: agitation, confusion
- Autonomic instability: hyperthermia, tachycardia, sweating
- Neuromuscular abnormalities: tremor, hyperreflexia, clonus
- Treatment: supportive care including IV fluids, temperature control, and benzodiazepines for agitation
- In severe cases, serotonin antagonists like cyproheptadine may be administered, with a typical dosage of 12 to 24 mg over 24 hours, 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.
Importance of Prompt Recognition and Treatment
Prompt recognition and treatment of serotonin syndrome are crucial to prevent severe complications, including rhabdomyolysis, metabolic acidosis, elevated serum aminotransferase, renal failure, seizures, and disseminated intravascular coagulopathy 1. The Hunter criteria are commonly used for clinical diagnosis, and testing may be obtained based on clinical suspicion, including complete blood cell count, electrolytes, serum urea nitrogen, creatinine, arterial blood gas, hepatic transaminases, creatine kinase, urinalysis, toxicology screens, coagulation studies, electrocardiography, EEG, and brain imaging studies 1. Discontinuing the precipitating agent and providing supportive care are the mainstays of treatment, with serotonin antagonists like cyproheptadine considered in severe cases.
From the Research
Definition and Causes of Serotonin Syndrome
- Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system 2, 3, 4.
- It is characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity 2.
- The syndrome can be caused by the use of multiple serotonergic drugs or considerable exposure to a single serotonin-augmenting drug 2, 3, 4.
- The combination of a monoamine oxidase inhibitor (MAOI) with serotonergic drugs is especially dangerous and may lead to the most severe form of the syndrome 4.
Diagnosis and Clinical Features
- Diagnosis is made using the Hunter Serotonin Toxicity Criteria, 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 2.
- Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis 3.
- The syndrome can range in severity from mild to life-threatening 3, 4.
- Patients present with a combination of neuromuscular, autonomic, and mental status symptoms 5.
Management and Treatment
- Most cases of serotonin syndrome are mild and may be treated by withdrawal of the offending agent and supportive care 2, 3.
- Benzodiazepines may be used to treat agitation and tremor 2.
- Cyproheptadine may be used as an antidote 2, 3.
- Patients with moderate or severe cases of serotonin syndrome require hospitalization and may need neuromuscular paralysis, sedation, and intubation 2.
- Management of serotonin syndrome involves withdrawal of the offending agent(s), aggressive supportive care to treat hyperthermia and autonomic dysfunction, and occasionally the administration of serotonin antagonists--cyproheptadine or chlorpromazine 3.
Prevention
- Psychiatrists, clinicians, and general practitioners must develop increased awareness of serotonin syndrome due to the current increase in the use of serotonergic agents in clinical practice 3.
- Family physicians play a key role in identifying and preventing serotonin syndrome by teaching patients to recognize symptoms and monitoring patients throughout therapy 5.
- The use of serotonergic agents should be carefully monitored, and patients should be educated on the risks of serotonin syndrome 6.