What are the symptoms of serotonin syndrome?

Symptoms of Serotonin Syndrome

Serotonin syndrome presents with a triad of symptoms including altered mental status, autonomic instability, and neuromuscular abnormalities, with key diagnostic features being clonus, hyperreflexia, and hyperthermia in patients who have taken serotonergic medications. 1

Clinical Presentation

Serotonin syndrome manifests across a spectrum of severity from mild to life-threatening. The symptoms can be categorized into three main domains:

Mental Status Changes

• Anxiety
• Agitation
• Confusion
• Altered consciousness

Autonomic Dysfunction

• Hyperthermia (temperature >38°C)
• Tachycardia
• Diaphoresis (excessive sweating)
• Blood pressure fluctuations
• Flushing
• Urinary incontinence

Neuromuscular Abnormalities

• Hyperreflexia (most common)
• Clonus (spontaneous, inducible, or ocular)
• Tremor
• Muscle rigidity
• Myoclonus
• Positive Babinski sign
• Chorea
• Trismus
• Oculogyric crisis 1, 2

Diagnostic Criteria

The Hunter Serotonin Toxicity Criteria are considered the diagnostic standard for serotonin syndrome. These criteria require:

1. Patient has taken a serotonergic drug within the past 5 weeks
2. Patient exhibits one or more of the following:
   • Spontaneous clonus
   • Inducible clonus with agitation or diaphoresis
   • Ocular clonus with agitation or diaphoresis
   • Tremor and hyperreflexia
   • Hypertonia, temperature >38°C, and ocular or inducible clonus 1, 2

The Hunter criteria have higher specificity than the older Sternbach criteria, with clonus being particularly specific for serotonin syndrome 3.

Severity Classification

Serotonin syndrome can be classified by severity:

Mild

• Mild symptoms that may not concern the patient
• Often resolves with withdrawal of the offending agent

Moderate

• Significant distress requiring treatment
• Not immediately life-threatening
• May include more pronounced autonomic effects and neurological symptoms

Severe (Medical Emergency)

• Rapid onset of severe hyperthermia (>41°C)
• Severe muscle rigidity
• Multiple organ failure
• Approximately 25% of severe cases require intubation and mechanical ventilation 1, 3

Laboratory Findings

Serotonin syndrome may present with various laboratory abnormalities:

• Leukocytosis
• Elevated creatine kinase
• Electrolyte abnormalities
• Elevated liver enzymes
• Metabolic acidosis 1

Common Pitfalls and Caveats

1. Misdiagnosis: The symptoms of serotonin syndrome are diverse and nonspecific, which can lead to misdiagnosis 4. It's often confused with neuroleptic malignant syndrome, malignant hyperthermia, or anticholinergic toxicity.

2. Medication Combinations: The risk significantly increases when combining multiple serotonergic medications, particularly MAOIs with any serotonergic drug 1. Be vigilant when patients are on multiple medications with serotonergic effects.

3. Delayed Recognition: Failure to promptly recognize and treat serotonin syndrome can lead to serious complications including rhabdomyolysis, renal failure, disseminated intravascular coagulation, seizures, and death, with an approximately 11% mortality rate without proper treatment 1.

4. Medication Sources: Remember that various medications beyond antidepressants can contribute to serotonin syndrome, including opioids, stimulants, over-the-counter medications containing dextromethorphan or chlorpheniramine, certain antibiotics, and herbal supplements 1.

5. Onset Timing: Symptoms typically develop rapidly, often within 24 hours of medication changes or additions 2.

By recognizing these symptoms early and understanding the diagnostic criteria, clinicians can promptly identify serotonin syndrome and initiate appropriate management to prevent serious complications.