A 55-year-old woman is evaluated in the hospital for new-onset agitation, sweating, and tr… — USMLE Step 2 CK

A 55-year-old woman is evaluated in the hospital for new-onset agitation, sweating, and tremors. She was admitted three days ago for a severe soft tissue infection and was recently transitioned to intravenous linezolid due to bacterial sensitivities. Her past medical history is significant for major depressive disorder, generalized anxiety disorder, hypertension, and hyperlipidemia. Her temperature is $38.8^\circ\text{C}$ ( $101.8^\circ\text{F}$ ), blood pressure is $158/96\text{ mm Hg}$ , and pulse is $118/\text{min}$ . Physical examination reveals a prominently diaphoretic and agitated woman. Neurologic examination demonstrates inducible clonus in the bilateral ankles and generalized hyperreflexia. An interaction involving linezolid and which of the following home medications is the most likely cause of this patient's current symptoms?

A
Bupropion
ParoxetineAnswer
C
Losartan
D
Lorazepam
E
Atorvastatin

Answer

Paroxetine

Linezolid is an oxazolidinone antibiotic that uniquely possesses reversible, non-selective monoamine oxidase inhibitor (MAOI) activity. When linezolid is administered to a patient taking a selective serotonin reuptake inhibitor (SSRI) like paroxetine, the combination of inhibited serotonin reuptake and inhibited serotonin degradation leads to an acute, severe excess of synaptic serotonin. This manifests clinically as serotonin syndrome, characterized by the triad of autonomic instability (hyperthermia, tachycardia, diaphoresis), altered mental status (agitation), and neuromuscular hyperactivity (hyperreflexia, clonus).

Step-by-Step Solution

Identify the clinical syndrome based on the patient's acute physical findings.

The patient exhibits autonomic instability (fever, tachycardia, hypertension), altered mental status (agitation), and neuromuscular hyperactivity (hyperreflexia, inducible clonus), which form the classic triad of serotonin syndrome.

Recognizing the diagnostic features of serotonin syndrome is the first step in identifying the responsible pharmacological agents.

Analyze the patient's recent medication changes in the context of her psychiatric history.

The patient was recently started on linezolid. Her history of major depressive disorder and generalized anxiety disorder strongly suggests she is taking a home antidepressant.

Establishing the temporal relationship between a newly administered drug and symptom onset highlights a potential adverse drug-drug interaction.

Determine which class of home medication interacts with linezolid to precipitate this specific syndrome.

Linezolid is an antibiotic that also functions as a reversible, non-selective monoamine oxidase inhibitor (MAOI). When combined with a selective serotonin reuptake inhibitor (SSRI) like paroxetine, it prevents serotonin breakdown while reuptake is blocked, causing massive synaptic serotonin excess.

Understanding the hidden mechanisms of action of common medications is crucial for preventing severe iatrogenic complications.

Key Concept

Serotonin syndrome can be life-threatening and is frequently precipitated by the concurrent use of a selective serotonin reuptake inhibitor (SSRI) and linezolid, an antibiotic that also possesses monoamine oxidase inhibitor (MAOI) properties.

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