What is serotonin syndrome?

From the Guidelines

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin levels in the body, typically resulting from medication interactions, and requires immediate discontinuation of all serotonergic medications and emergency medical care. The condition can be caused by a variety of medications, including SSRIs (like fluoxetine, sertraline), SNRIs (venlafaxine, duloxetine), MAOIs (phenelzine), triptans (sumatriptan), certain antibiotics (linezolid), and illicit drugs (MDMA, cocaine) 1. Symptoms of serotonin syndrome develop rapidly and include the classic triad of:

• Altered mental status (agitation, confusion)
• Autonomic instability (high fever, sweating, tachycardia, hypertension)
• Neuromuscular abnormalities (tremor, rigidity, hyperreflexia, clonus)

Treatment of serotonin syndrome focuses on supportive care, including IV fluids and benzodiazepines for agitation 1. Severe cases may require serotonin antagonists like cyproheptadine (initial dose 12mg orally, then 2mg every 2 hours until symptoms improve) and intensive care monitoring 1. Prevention is crucial through careful medication reconciliation, avoiding high-risk combinations, and educating patients about potential interactions, including over-the-counter medications and supplements like St. John's wort that can increase serotonin levels 1. It is essential to note that serotonin syndrome can deteriorate rapidly, and close observation and preparation for rapid intervention may be necessary 1.

In terms of diagnosis, the Hunter criteria are commonly used to diagnose serotonin syndrome, which includes the presence of any of the following: tremor and hyperreflexia; spontaneous clonus; muscle rigidity, temperature >38°C, and either ocular clonus or inducible clonus; ocular clonus and either agitation or diaphoresis; or inducible clonus and either agitation or diaphoresis 1. The incidence of and mortality from serotonin syndrome have been increasing, and it is essential to be aware of the growing number and use of proserotonergic medications that can contribute to this condition 1.

Overall, serotonin syndrome is a serious condition that requires prompt recognition and treatment to prevent morbidity and mortality. Immediate discontinuation of all serotonergic medications and emergency medical care is crucial in managing serotonin syndrome.

From the Research

Definition and Causes of Serotonin Syndrome

• Serotonin syndrome (SS) is a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system 2, 3, 4.
• It is characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity 3.
• SS can result from excessive serotonergic activity, often due to selective serotonin reuptake inhibitors (SSRIs), drug-drug interactions, or dose-related effects 5.
• The syndrome can occur after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors 4.

Clinical Features of Serotonin Syndrome

• The clinical features of SS include alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity 4.
• Common clinical features include hyperreflexia, clonus, tachycardia, tremor, rigidity, increased bowel sound, diaphoresis, fever, hypertension, and myoclonus 2.
• The diagnosis of SS is made using the Hunter Serotonin Toxicity Criteria, which require the presence of specific classical features or groups of features 3.

Management and Treatment of Serotonin Syndrome

• The 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 such as cyproheptadine or chlorpromazine 3, 4.
• Cyproheptadine is a serotonin antagonist that can be used to treat SS, and its use has been shown to be effective in resolving symptoms 2, 6.
• Benzodiazepines may be used to treat agitation and tremor, while guanfacine and gabapentin may be used to mitigate glutamatergic activity 5.
• Patients with moderate or severe cases of SS require hospitalization, and critically ill patients may require neuromuscular paralysis, sedation, and intubation 3.