What is serotonin syndrome?

From the Guidelines

Serotonin syndrome is a medical emergency that requires immediate discontinuation of the precipitating agent and supportive care, with severe cases necessitating emergency sedation, neuromuscular paralysis, and intubation, as well as consideration of serotonin2A antagonists like cyproheptadine 1. The condition is characterized by a triad of symptoms: mental status changes, autonomic instability, and neuromuscular abnormalities, which can be life-threatening if not promptly recognized and treated.

Key Considerations

• Discontinuation of the precipitating agent is crucial in managing serotonin syndrome, as it helps to reduce serotonin levels and alleviate symptoms 1.
• Supportive care, including treatment of agitation with benzodiazepines, amelioration of hyperthermia, and management of autonomic instability with IV fluids and other agents, is essential in managing the condition 1.
• Severe cases of serotonin syndrome may require intensive supportive care, including emergency sedation, neuromuscular paralysis, and intubation, as well as consideration of serotonin2A antagonists like cyproheptadine 1.
• The use of physical restraints is generally discouraged, as it can exacerbate isometric contractions, worsen hyperthermia and lactic acidosis, and increase mortality 1.

Treatment Options

• Benzodiazepines are commonly used to treat agitation and tremor in patients with serotonin syndrome 1.
• Cyproheptadine, a serotonin2A antagonist, may be considered in severe cases, with an initial dose of 12mg orally, followed by 2mg every 2 hours until improvement 1.
• Intensive supportive care, including mechanical ventilation and admission to an ICU, may be necessary in severe cases 1.

Diagnostic Criteria

• The Hunter criteria are commonly used to diagnose serotonin syndrome, although there are no pathognomonic laboratory or radiographic findings 1.
• Clinical suspicion and testing, including complete blood cell count, electrolytes, serum urea nitrogen, creatinine, arterial blood gas, and hepatic transaminases, may be necessary to support the diagnosis 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.
• 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 medications 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.
• 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.
• Benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels 3.
• In severe cases, higher cyproheptadine doses than currently recommended may be necessary, and patients may benefit from propofol or both 4.
• The benefits of and indications for cyproheptadine are uncertain and questionable for the management of a serotonin syndrome, and future recommendations on its use should be based on diagnostic criteria, severity of symptoms, and management in conjunction with other supportive measures 5.

Prevention and Awareness

• Psychiatrists, clinicians, and general practitioners must develop increased awareness of SS due to the current increase in the use of serotonergic agents in clinical practice 2.
• There is a need for regular information updates and reminders to all those who prescribe medications to patients about the condition or drugs associated with it 3.
• SS is a manifestation of adverse pharmacology, making it predictable and highly preventable, and most cases of SS are mild and easily managed with prompt recognition and supportive care 2.