What are the signs of serotonin syndrome in a patient taking fluoxetine 30 mg daily and trazodone 150 mg nightly who has intermittent hand‑foot spasms?

Signs of Serotonin Syndrome

Serotonin syndrome presents as a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities—with clonus and hyperreflexia being the most diagnostic features when occurring in patients taking serotonergic medications. 1

Clinical Triad

Mental Status Changes

• Agitated delirium is the most common mental status alteration 1
• Confusion ranging from mild disorientation to complete altered consciousness 1
• In severe cases, patients may progress to coma 1

Neuromuscular Abnormalities (Most Diagnostic)

• Clonus (spontaneous, inducible, or ocular) is highly diagnostic and a key feature 1, 2
• Hyperreflexia is characteristically present and helps distinguish from other conditions 1, 2
• Myoclonus (involuntary muscle jerking) 1, 3
• Tremor, particularly in combination with hyperreflexia 1, 4
• Muscle rigidity (in severe cases) 1, 4

Autonomic Hyperactivity

• Hyperthermia (temperature can reach up to 41.1°C in severe cases) 1
• Tachycardia and tachypnea 1
• Hypertension or blood pressure fluctuations (≥20 mm Hg diastolic or ≥25 mm Hg systolic change within 24 hours) 1
• Profuse diaphoresis (sweating) 1, 5, 6
• Mydriasis (dilated pupils) 1

Diagnostic Criteria (Hunter Criteria - Preferred)

The American Academy of Pediatrics recommends using the Hunter Criteria, which require a serotonergic agent plus one of the following: 1, 2

• Spontaneous clonus, OR
• Inducible clonus with agitation or diaphoresis, OR
• Ocular clonus with agitation or diaphoresis, OR
• Tremor and hyperreflexia together, OR
• Hypertonia with temperature >38°C and either ocular or inducible clonus

Timing and Onset

• Symptoms typically develop within 6-24 hours after starting a serotonergic medication, increasing the dose, or adding a second serotonergic agent 1, 2
• Most cases manifest within minutes to hours of the precipitating change 1
• The condition is non-idiosyncratic, meaning it can predictably occur with drug combinations or dose escalations 1

Context-Specific Considerations for Your Patient

In a patient taking fluoxetine 30 mg daily and trazodone 150 mg nightly with intermittent hand-foot spasms:

• Evaluate specifically for clonus (not just spasms)—test for inducible ankle clonus by rapidly dorsiflexing the foot 1, 2
• Check for hyperreflexia at the knees and ankles, which would be highly suggestive when combined with the medication regimen 1
• Assess for accompanying diaphoresis, agitation, or confusion 1, 5
• The combination of an SSRI (fluoxetine) with trazodone carries moderate risk for serotonin syndrome, particularly if doses were recently increased 7, 5, 6

Critical Pitfalls to Avoid

• Do not confuse simple muscle spasms with clonus—true clonus is rhythmic, involuntary muscle contractions triggered by sudden passive stretch 1
• Mild cases are easily missed because the presentation is highly variable 1
• The condition can deteriorate rapidly, so close observation is essential even if initial symptoms seem mild 1
• Antipyretics are ineffective for the hyperthermia because fever results from muscular hyperactivity, not hypothalamic dysregulation 1, 2

Distinguishing from Other Conditions

• Neuroleptic malignant syndrome presents with lead-pipe rigidity and normal or decreased reflexes (versus hyperreflexia in serotonin syndrome) 1, 2
• History of antipsychotic use points to NMS rather than serotonin syndrome 1

Severe Complications (11% Mortality Rate)

• Rhabdomyolysis with markedly elevated creatine kinase 1, 5
• Metabolic acidosis 1
• Acute renal failure 1
• Seizures 1
• Disseminated intravascular coagulation 1
• Multiple organ failure in cases with severe hyperthermia >41.1°C 1, 4