A 32-year-old woman on fluoxetine 40 mg daily for depression is started on tramadol 50 mg for acute musculoskeletal pain. Within 6 hours, she develops tremor, hyperreflexia, mydriasis, and agitation. Which of the following is NOT a feature of serotonin syndrome?

Explanation

## Serotonin Syndrome: Clinical Features **Key Point:** Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity. It presents with a classic triad of mental status changes, autonomic instability, and neuromuscular abnormalities. ### Classic Neuromuscular Features **High-Yield:** The neuromuscular manifestations of serotonin syndrome include: - **Hyperreflexia** (brisk or exaggerated deep tendon reflexes) - **Muscle rigidity** and hypertonicity, particularly in the lower extremities - **Tremor** (fine tremor of hands and feet) - **Myoclonus** and spontaneous muscle twitches - **Ocular clonus** (rhythmic eye movements) **Hyporeflexia and diminished reflexes are NOT features of serotonin syndrome.** This is a critical distinguishing point from neuroleptic malignant syndrome (NMS), which can present with either normal or decreased reflexes depending on severity. ### Autonomic and Mental Status Features | Feature Category | Manifestations | |---|---| | **Autonomic** | Hyperthermia, diaphoresis, tachycardia, hypertension, mydriasis | | **Mental Status** | Agitation, anxiety, confusion, restlessness, insomnia | | **GI** | Diarrhea, nausea, vomiting (common early sign) | ### Comparison: Serotonin Syndrome vs. NMS | Feature | Serotonin Syndrome | NMS | |---|---|---| | **Onset** | Hours to days | Days to weeks | | **Reflexes** | **Hyperreflexia** | Normal or decreased | | **Diarrhea** | Common | Rare | | **Tremor** | Fine tremor, myoclonus | Cogwheel rigidity | | **Trigger** | Serotonergic drugs | Antipsychotics | **Clinical Pearl:** The presence of hyperreflexia and myoclonus strongly favors serotonin syndrome, whereas decreased reflexes would suggest NMS or spinal cord pathology. **Mnemonic — SEROTONIN SYNDROME FEATURES: MADDEST** - **M**yoclonus and muscle rigidity - **A**gitation and altered mental status - **D**iaphoresis and diarrhea - **D**ilated pupils (mydriasis) - **E**levated temperature (hyperthermia) - **S**peedy reflexes (hyperreflexia) - **T**remor - **H**ypertension and tachycardia [cite:Harrison 21e Ch 396]