Pharmacology · Year 2 · from Pharmacology

Case 3: Serotonin Syndrome

Clinical Scenario

A 45-year-old female presents with agitation, tremor, and fever after her psychiatrist added tramadol to her existing sertraline regimen.

Patient Demographics

• Age: 45 years
• Sex: Female
• Weight: 68 kg

Chief Complaint

Confusion, shakiness, and feeling "overheated" for 8 hours

History of Present Illness

The patient has major depressive disorder treated with sertraline 150 mg daily for 2 years. Three days ago, her psychiatrist added tramadol 50 mg three times daily for chronic low back pain. She began experiencing restlessness, profuse sweating, and muscle twitching yesterday, which have worsened today. Her husband notes she seems confused and has had diarrhea.

Medications

• Sertraline 150 mg daily
• Tramadol 50 mg TID (started 3 days ago)

Physical Examination

• Vital Signs: BP 165/95 mmHg, HR 118 bpm, RR 22, T 39.8C
• General: Agitated, diaphoretic, confused
• HEENT: Mydriasis (6 mm bilaterally), dry mucous membranes
• Neurological:
• Hyperreflexia (3+ throughout)
• Spontaneous clonus at ankles bilaterally
• Muscle rigidity (legs > arms)
• Tremor
• Ocular clonus present
• Abdominal: Hyperactive bowel sounds, diarrhea
• Skin: Diaphoretic, flushed

Workup and Results

Note: Tramadol cross-reacts with amphetamine immunoassays

Diagnosis

Serotonin syndrome - Hunter Criteria met (serotonergic agent + spontaneous clonus)

CNS Pharmacology Principles Illustrated

1. Serotonin excess: Tramadol inhibits serotonin reuptake (like an SSRI) while sertraline does the same, causing excessive synaptic serotonin.
2. Hunter Criteria: More specific than older criteria; clonus is central to diagnosis.
3. Neuromuscular excitation: Hyperreflexia, clonus, tremor, and rigidity distinguish from other conditions.
4. Drug combinations: SSRI + tramadol, SSRI + MAOI, or SSRI + triptans are high-risk combinations.
5. Rapid onset: Typically develops within 24 hours of drug change.

Treatment

1. Discontinue all serotonergic agents immediately
2. Supportive care:

• Cooling measures for hyperthermia
• IV fluids for dehydration
• Benzodiazepines (lorazepam 2 mg IV) for agitation and muscle rigidity

1. Cyproheptadine: 12 mg PO initial dose, then 2 mg every 2 hours for ongoing symptoms (serotonin antagonist)
2. Consider intubation if severe hyperthermia or rigidity
3. Avoid restraints (can worsen hyperthermia)
4. Monitor CK and renal function for rhabdomyolysis
5. Symptoms typically resolve within 24-72 hours with supportive care

Key Differential Diagnosis

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