From the Guidelines
Serotonin syndrome is a life-threatening condition characterized by excessive serotonin levels, presenting with altered mental status, autonomic instability, and neuromuscular abnormalities, and requires immediate discontinuation of the precipitating agent and supportive care. The signs and symptoms of serotonin syndrome can vary from mild to severe and typically develop within hours of taking a new serotonergic medication or increasing the dose of an existing one 1. The classic triad includes:
- Altered mental status (confusion, agitation, hallucinations)
- Autonomic instability (hyperthermia, tachycardia, diaphoresis, dilated pupils, fluctuating blood pressure)
- Neuromuscular abnormalities (tremor, clonus, hyperreflexia, muscle rigidity)
Mild cases may present with mild hypertension, tachycardia, mydriasis, diaphoresis, shivering, tremor, myoclonus, and hyperreflexia, while moderate cases may show more pronounced vital sign abnormalities, hyperthermia up to 40°C, hyperactive bowel sounds, ocular clonus, and agitation 1. Severe cases involve temperatures above 41°C, dramatic blood pressure fluctuations, delirium, muscle rigidity, and can progress to seizures, rhabdomyolysis, metabolic acidosis, renal failure, and death 1. Common medications that can trigger serotonin syndrome include SSRIs, SNRIs, TCAs, MAOIs, triptans, certain opioids (tramadol, fentanyl), dextromethorphan, and illicit drugs like MDMA. Treatment involves discontinuing the offending agent, supportive care, and in severe cases, serotonin antagonists like cyproheptadine, which is usually administered at a dose of 12 to 24 mg over 24 hours 1.
The Hunter criteria are commonly used for clinical diagnosis, and testing may be obtained based on clinical suspicion, including a 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. It is essential to note that not all patients will have all the classic signs and symptoms, and treatment should be individualized based on the severity of the condition and the patient's response to therapy 1.
From the Research
Serotonin Syndrome Signs and Symptoms
- Alteration of mental status, such as agitation, confusion, and changes in mood 2, 3, 4
- Abnormalities of neuromuscular tone, including muscle rigidity, tremors, and sweating 2, 3, 4
- Autonomic hyperactivity, characterized by rapid heart rate, high blood pressure, dilated pupils, and diarrhea 2, 3, 4
- Hyperthermia, although not always present 5
- Seizures, shock, and death can occur if left untreated 5
Clinical Manifestations
- Diverse and nonspecific, which may lead to misdiagnosis 2
- Can range in severity from mild to life-threatening 2, 3, 4
- May occur after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors 2, 3, 4
Diagnosis and Management
- Diagnosis based on the presence of clinical symptoms and relevant drug history 3, 5
- Management involves withdrawal of the offending agent(s), aggressive supportive care, and occasionally the administration of serotonin antagonists 2, 3, 6
- Benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels 3, 6