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 most recent and highest quality study 1. The primary goal of treatment is to reduce serotonin levels and manage symptoms.

• Discontinuation of the precipitating agent is crucial, as it helps to decrease serotonin levels and prevent further exacerbation of the syndrome.
• 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 symptoms and prevent complications 1.
• For moderate to severe cases, cyproheptadine, a serotonin antagonist, is the primary pharmacologic treatment, with a recommended dose of 12 mg orally initially, followed by 2 mg every 2 hours until symptoms improve, then 8 mg every 6 hours (maximum 32 mg/day) 1.
• In severe cases, intensive care with mechanical ventilation, active cooling measures for hyperthermia, intravenous fluids for hydration, and continuous cardiac monitoring may be necessary, as well as neuromuscular paralysis with agents like vecuronium in extreme cases with severe hyperthermia and rigidity 1.
• It is essential to note that physical restraints may be detrimental, as they can exacerbate isometric contractions, worsen hyperthermia and lactic acidosis, and increase mortality, as highlighted in the study 1.
• The mortality rate for serotonin syndrome is approximately 11%, with significant morbidity and mortality associated with the condition, emphasizing the need for prompt and effective treatment 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 key components, including:

• Withdrawal of the offending agent(s) [ 3, 4, 5, 6 ]
• Aggressive supportive care to treat hyperthermia and autonomic dysfunction [ 3, 4, 6 ]
• Administration of serotonin antagonists, such as cyproheptadine or chlorpromazine [ 3, 4, 7, 5, 6 ]
• Benzodiazepines may be used to treat agitation and tremor [ 4 ]

Management of Serotonin Syndrome

Management of serotonin syndrome depends on the severity of the condition:

• Mild cases: may be treated by withdrawal of the offending agent and supportive care [ 3, 4 ]
• Moderate or severe cases: require hospitalization and may require neuromuscular paralysis, sedation, and intubation [ 3, 4 ]
• Critically ill patients: may require aggressive treatment, including external cooling and paralysis [ 6 ]

Use of Cyproheptadine

Cyproheptadine is a serotonin antagonist that may be used as an antidote for serotonin syndrome:

• The dosing schedule for cyproheptadine is not uniform in the literature [ 7 ]
• A loading dose of 12 mg followed by 2 mg every 2 h for at least 24 h may be used in severe cases [ 7 ]
• A dose of 4 mg three times a day may be used in mild cases [ 7 ]