What is the treatment for serotonin syndrome?

From the Guidelines

Treatment for serotonin syndrome requires immediate discontinuation of all serotonergic medications and supportive care, with benzodiazepines and cyproheptadine being key components of management, as evidenced by the 2016 Pediatrics study 1. The goal of treatment is to reduce serotonin levels, manage symptoms, and prevent complications.

• Discontinuation of the precipitating agent is crucial, as it can help alleviate symptoms within 24-72 hours.
• Supportive care, including treatment of agitation with benzodiazepines, such as lorazepam (1-2 mg IV every 2-4 hours as needed) or diazepam (5-10 mg IV), is essential to control autonomic instability and prevent further complications 1.
• For moderate to severe cases, cyproheptadine, a serotonin antagonist, is recommended at an initial dose of 12 mg orally, followed by 2 mg every 2 hours until symptoms improve, then 8 mg every 6 hours until complete resolution (maximum 32 mg/day) 1.
• Severe cases may require intensive care with mechanical ventilation, paralysis with non-depolarizing agents like vecuronium to control muscle rigidity and hyperthermia, active cooling measures, and management of complications like rhabdomyolysis or DIC 1.
• Intravenous fluids should be given to maintain hydration and renal function, and physical restraints should be avoided as they can exacerbate isometric contractions, worsening hyperthermia and lactic acidosis, and increasing mortality 1. Key considerations in treatment include:
• Monitoring for signs of severe serotonin syndrome, such as temperature >41.1°C, and being prepared to escalate care to intensive care units (ICUs) if necessary 1.
• Recognizing that approximately one-quarter of patients may require intubation, mechanical ventilation, and admission to an ICU, with a mortality rate of approximately 11% 1.
• Being aware that serotonin syndrome can present with altered mental status, autonomic dysfunction, and neuromuscular abnormalities, and that treatment should be tailored to the individual patient's symptoms and severity of illness 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Cyproheptadine is a serotonin and histamine antagonist with anticholinergic and sedative effects. The treatment for serotonin syndrome is cyproheptadine, a serotonin antagonist, which can be administered orally (PO) 2.

• The drug works by competing with serotonin for receptor sites, thereby counteracting the effects of excess serotonin.
• Cyproheptadine is specifically used to treat serotonin syndrome due to its antiserotonin properties.

From the Research

Treatment Overview

The treatment for serotonin syndrome involves several approaches, including:

• Withdrawal of the offending agent(s) [ 3, 4, 5 ]
• Supportive care to treat hyperthermia and autonomic dysfunction [ 3, 4, 5 ]
• Administration of serotonin antagonists, such as cyproheptadine [ 3, 6, 4, 5, 7 ]
• Benzodiazepines may be used to treat agitation and tremor [ 3 ]
• Patients with moderate or severe cases may require hospitalization, neuromuscular paralysis, sedation, and intubation [ 3 ]

Cyproheptadine Treatment

Cyproheptadine is a commonly used antidote for serotonin syndrome, with various dosing regimens reported:

• A loading dose of 12 mg followed by 2 mg every 2 hours for at least 24 hours [ 6 ]
• 4 mg three times a day [ 6 ]
• A total dose of 188 mg over 10 days, with no reported side effects [ 7 ]
• Response to cyproheptadine within 24 hours can be a diagnostic indicator of serotonin syndrome [ 6 ]

Hospitalization and Supportive Care

Patients with moderate or severe serotonin syndrome require hospitalization and aggressive supportive care:

• Treatment of hyperthermia and autonomic dysfunction [ 3, 4 ]
• Monitoring of vital signs and clinical status [ 3, 4 ]
• Supportive care, such as fluid replacement and oxygen therapy, as needed [ 3, 4 ]