From the Guidelines
Serotonin syndrome is a life-threatening condition that requires immediate discontinuation of all serotonergic medications and emergency medical care, with treatment involving supportive care, benzodiazepines for agitation, and in severe cases, serotonin antagonists like cyproheptadine. The syndrome 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, and certain pain medications, such as tramadol and fentanyl 1. The clinical presentation of serotonin syndrome can be extremely variable, making diagnosis challenging, but the Hunter criteria are commonly used for diagnosis 1. Treatment involves discontinuing the precipitating agent, providing supportive care, and using benzodiazepines for agitation, with serotonin antagonists like cyproheptadine used in severe cases, and cooling measures may be needed for hyperthermia 1. Prevention is crucial by avoiding combinations of serotonergic medications and maintaining appropriate washout periods when switching between these drugs, and patients should be advised to avoid sudden cessation or rapid dose reduction of daily dosed SSRIs to prevent SSRI withdrawal syndrome 1. It is essential to recognize the symptoms of serotonin syndrome, which include clonus, tremor, hyperreflexia, agitation, mental status changes, diaphoresis, and fever, and to treat it promptly to prevent severe complications, such as seizure and rhabdomyolysis 1. In summary, serotonin syndrome is a potentially life-threatening condition that requires immediate medical attention, and treatment involves discontinuing serotonergic medications, providing supportive care, and using benzodiazepines and serotonin antagonists as needed.
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.
- This excessive serotonin hyperstimulation may be secondary to a standard therapeutic dose of a single agent, inadvertent interactions between various drugs, intentionally or unintentionally excessive use of particular drugs, deliberate self-harm, or recreational use of certain drugs 2.
- SS can occur when serotonergic medicines are taken alone or in combination, especially when a new medication is added, or the dose of an existing medication is changed 3.
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.
- However, all 3 triads of SS may not occur simultaneously, and clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis 2.
- 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.
Management and Treatment
- 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--cyproheptadine or chlorpromazine 2.
- In severe cases, benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels 3, 4.
- Classic antihypertensives may not be effective for the treatment of severe hypertension associated with serotonin syndrome, and patients with severe hypertension not responding to benzodiazepines may benefit from cyproheptadine, propofol or both 4.
Prognosis and Prevention
- Most cases of SS are mild and resolve with prompt recognition and supportive care 2.
- With prompt recognition and supportive care, more severe cases of SS have a favorable prognosis 2.
- There is a need for regular information updates and reminders to all those who prescribe medications to patients to increase awareness of SS and prevent this potentially fatal condition 3.