What is serotonin syndrome?

From the Guidelines

Serotonin syndrome is a life-threatening medical condition caused by an excess of serotonin in the body, typically resulting from medication interactions, and requires immediate discontinuation of serotonergic medications and emergency medical attention. The condition is characterized by a triad of symptoms: mental status changes, autonomic instability, and neuromuscular abnormalities, as described in the study published in Pediatrics in 2016 1. Common causative agents include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, and certain antibiotics like linezolid.

Key Characteristics of Serotonin Syndrome

• Mental status changes: agitation, confusion
• Autonomic instability: hyperthermia, tachycardia, sweating
• Neuromuscular abnormalities: tremor, hyperreflexia, clonus

Treatment and Management

Treatment involves supportive care, benzodiazepines for agitation, and in severe cases, serotonin antagonists like cyproheptadine, with an initial dose of 12mg orally, followed by 2mg every 2 hours until symptoms improve, as recommended in the study 1. Cooling measures may be needed for hyperthermia.

Prevention and Medication Reconciliation

Prevention is crucial through careful medication reconciliation and avoiding combinations of serotonergic drugs, as emphasized in the study 1. Serotonin syndrome occurs because these medications increase synaptic serotonin by blocking reuptake, increasing release, or inhibiting metabolism, leading to overstimulation of central and peripheral serotonin receptors, particularly 5-HT1A and 5-HT2A receptors.

Clinical Diagnostic Criteria

Clinical diagnostic criteria for serotonin syndrome have been proposed, with Hunter criteria being most commonly used, as mentioned in the study 1. The study also highlights the importance of testing and laboratory findings, including complete blood cell count, electrolytes, serum urea nitrogen, creatinine, arterial blood gas, hepatic transaminases, creatine kinase, urinalysis, toxicology screens, coagulation studies, electrocardiography, EEG, and brain imaging studies, in diagnosing and 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, 5, 6.
• It is characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity 4.
• SS can be caused by the use of multiple serotonergic drugs or significant exposure to a single serotonin-augmenting drug 4.
• The condition can also occur at therapeutic dosages, and patients may continue to use serotonergic medications even if they develop mild to moderate SS 5.

Clinical Features of Serotonin Syndrome

• The clinical features of SS include neuromuscular excitation (tremor, hyperreflexia, and clonus), autonomic dysfunction (tachycardia, hypertension/hypotension, and hyperthermia), and altered mental status (agitation, delirium, and coma) 3.
• Other common clinical features include rigidity, increased bowel sound, diaphoresis, fever, hypertension, and myoclonus 2.
• The Hunter Serotonin Toxicity Criteria are used to diagnose SS, which require the presence of one of the following classical features or groups of features: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor and hyperreflexia, or hypertonia, temperature above 100.4 degrees F (38 degrees C), and ocular or inducible clonus 4.

Diagnosis and Treatment of Serotonin Syndrome

• Diagnosis is made using the Hunter Serotonin Toxicity Criteria, and treatment involves stopping the offending agent and supportive care, which focuses on agitation control, monitoring for and treating hyperthermia, and managing autonomic instability 3, 4.
• Benzodiazepines may be used to treat agitation and tremor, and cyproheptadine may be used as an antidote 4.
• Patients with moderate or severe cases of SS require hospitalization, and critically ill patients may require neuromuscular paralysis, sedation, and intubation 4.
• Prompt recognition and supportive care can lead to a favorable prognosis, but failure to make an early diagnosis and comprehend adverse pharmacological effects of therapy can lead to adverse outcomes 6.