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 medications that can trigger this condition include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and certain pain medications like tramadol.
Key Symptoms and Treatment
- Mental status changes: confusion, agitation
- Autonomic instability: high fever, sweating, rapid heart rate, high blood pressure
- Neuromuscular abnormalities: tremor, rigidity, hyperreflexia, clonus
- Treatment: supportive care, benzodiazepines for agitation, and in severe cases, serotonin antagonists like cyproheptadine (initial dose 12mg orally, followed by 2mg every 2 hours until symptoms improve) 1
Diagnosis and Management
Diagnosis is based on clinical suspicion and may include laboratory tests such as 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. The Hunter criteria are commonly used for clinical diagnostic criteria for serotonin syndrome. Discontinuing the precipitating agent and providing supportive care are crucial in managing serotonin syndrome, with approximately one-quarter of patients requiring intubation, mechanical ventilation, and admission to an ICU 1.
Medication Considerations
Cyproheptadine is usually administered orally, with a dosage of 12 to 24 mg over 24 hours, 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 1. The pediatric dosage is usually 0.25 mg/kg per day. It is essential to note that physical restraints may be detrimental, as they may exacerbate isometric contractions, thereby worsening hyperthermia and lactic acidosis and increasing mortality 1.
From the Research
Definition and Causes of Serotonin Syndrome
- Serotonin syndrome (SS) is a rare and potentially life-threatening toxic state caused by an adverse drug reaction that leads to excessive central and peripheral serotonergic activity 2.
- It can occur after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors 2, 3.
- The condition is caused by increased serotonin in the central nervous system (CNS), which can be due to various medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, stimulants, lithium, opioids, and certain herbal supplements 3, 4.
Clinical Features and Diagnosis
- SS classically consists of a triad of signs and symptoms broadly characterized as alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity 2.
- Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis 2, 5.
- The diagnosis of SS 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 3.
- The Hunter criteria, Sternbach criteria, and Radomski criteria are used to diagnose SS, but the Hunter criteria may not be the gold standard as they miss more cases than the other two criteria 5.
Management and Prevention
- Management of SS involves withdrawal of the offending agent(s), aggressive supportive care to treat hyperthermia and autonomic dysfunction, and occasionally the administration of serotonin antagonists, such as cyproheptadine or chlorpromazine 2, 3.
- In severe cases, benzodiazepines may be used to control agitation and muscle rigidity 3.
- Patients with moderate and severe cases of SS require inpatient hospitalization 2.
- Family physicians play a key role in identifying and preventing serotonin syndrome by teaching patients to recognize symptoms and monitoring patients throughout therapy 4.
- Regular information updates and reminders to all those who prescribe medications to patients are necessary to increase awareness of SS 3.