A patient on a high-dose SSRI develops confusion, agitation, hyperthermia, tachycardia, diaphoresis, hyperreflexia, and clonus after adding linezolid for a post-operative infection. This adverse drug interaction is most precisely explained by:
- A Linezolid's weak MAO-A inhibition combined with SSRI-mediated serotonin reuptake blockade causing excess synaptic serotonin — serotonin syndrome ✓
- B Linezolid inhibiting CYP3A4, causing SSRI accumulation and receptor overstimulation
- C Competitive displacement of the SSRI from albumin binding sites by linezolid, raising free drug levels
- D SSRI-induced CYP2C19 inhibition elevating linezolid plasma levels to toxic range
Explanation
Linezolid is a weak, reversible inhibitor of monoamine oxidase (both MAO-A and MAO-B). When combined with an SSRI (which blocks serotonin reuptake), the dual mechanism causes a massive accumulation of synaptic serotonin — the classic serotonin syndrome triad of autonomic instability, altered mental status, and neuromuscular abnormalities (hyperreflexia, clonus). This is a well-recognised and potentially life-threatening drug interaction; SSRIs are contraindicated with linezolid. Linezolid does not inhibit CYP3A4 or cause clinically meaningful protein displacement.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.