What are the signs of serotonin syndrome?

From the Guidelines

Serotonin syndrome is a life-threatening condition characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, and its signs include agitation, confusion, tremors, rigidity, excessive sweating, shivering, high fever, rapid heart rate, high blood pressure, dilated pupils, diarrhea, and headache, as reported in the most recent study 1. The clinical presentation of serotonin syndrome can be extremely variable, making diagnosis challenging, but the most common clinical finding is myoclonus, which occurs in slightly more than half of cases, according to a study published in Pediatrics 1. Some key points to consider when diagnosing serotonin syndrome include:

• Mental status changes, such as agitation, confusion, or hallucinations
• Autonomic hyperactivity, including hypertension, tachycardia, and diaphoresis
• Neuromuscular abnormalities, such as tremors, rigidity, or muscle jerking movements
• The presence of myoclonus, clonus, and hyperreflexia, which are highly diagnostic for serotonin syndrome, as noted in a study published in Pediatrics 1. The diagnosis of serotonin syndrome can be made using the Hunter criteria, which include 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, as described in a study published in Pediatrics 1. It is essential to differentiate serotonin syndrome from other medication-induced syndromes, such as neuroleptic malignant syndrome, malignant hyperthermia, and anticholinergic syndrome, as treatment may differ depending on the underlying etiology, as highlighted in a study published in Pediatrics 1. If serotonin syndrome is suspected, it is crucial to seek emergency medical attention immediately, as severe cases can be life-threatening, and treatment typically involves discontinuing the precipitating agent and providing supportive care, including benzodiazepines for agitation and management of autonomic instability, as reported in a study published in Pediatrics 1.

From the FDA Drug Label

Serotonin Syndrome This condition can be life-threatening and may include: agitation, hallucinations, coma or other changes in mental status coordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressure sweating or fever nausea, vomiting, or diarrhea muscle rigidity Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)

The signs of serotonin syndrome include:

• Mental status changes: agitation, hallucinations, delirium, coma
• Autonomic instability: tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia
• Neuromuscular symptoms: tremor, rigidity, myoclonus, hyperreflexia, incoordination
• Seizures
• Gastrointestinal symptoms: nausea, vomiting, diarrhea
• Coordination problems or muscle twitching (overactive reflexes)
• Racing heartbeat, high or low blood pressure
• Sweating or fever
• Muscle rigidity 2, 2

From the Research

Signs of Serotonin Syndrome

The signs of serotonin syndrome can be categorized into several groups, including:

• Alterations in mental status, such as:
  • Confusion 3, 4, 5, 6
  • Disorientation 6
  • Agitation 4, 7, 5, 6
  • Restlessness 6
• Autonomic instability, such as:
  • Fever 4, 5, 6
  • Shivering 4, 6
  • Diaphoresis 4, 5, 6
  • Diarrhea 4, 5, 6
  • High blood pressure 5
  • Rapid heart rate 5
  • Dilated pupils 5
• Neuromuscular abnormalities, such as:
  • Tremor 3, 4, 5
  • Hyperreflexia 3, 4, 7, 6
  • Myoclonus 3, 4, 7, 6
  • Ataxia 4, 6
  • Muscle rigidity 5
  • Sweating 5

Clinical Presentation

The clinical presentation of serotonin syndrome can vary, but it is often characterized by a constellation of symptoms that occur in the setting of recent addition of a serotonergic agent 4. The syndrome can range from mild to severe, and in some cases, it can be life-threatening 4, 5, 6.

Diagnosis and Management

The diagnosis of serotonin syndrome is based on the presence of clinical symptoms, and it is often caused by inadvertent use of serotonergic medicines 5. The management of serotonin syndrome typically involves discontinuing the use of the substance that caused the excess serotonin levels and providing supportive care, such as intravenous fluids and electrolytes 5. In severe cases, benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels 3, 4, 7, 5, 6.