A 32-year-old woman with treatment-resistant depression is started on augmentation with lithium. After 3 weeks she develops coarse tremor, polyuria, polydipsia, and mild cognitive slowing. Lithium toxicity is most likely because of concurrent use of:

• A Fluoxetine — inhibits renal lithium clearance
• B Ibuprofen — reduces prostaglandin E2-mediated inhibition of tubular lithium reabsorption ✓
• C Omeprazole — alkalinises urine promoting lithium ionisation and reduced clearance
• D Lorazepam — displaces lithium from plasma proteins causing free lithium surge

Explanation

NSAIDs like ibuprofen inhibit prostaglandin E2 synthesis in the renal medulla; PGE2 normally inhibits sodium (and therefore lithium) reabsorption in the thick ascending limb. With reduced PGE2, tubular lithium reabsorption increases, leading to lithium accumulation and toxicity. Lithium is not significantly protein-bound (so protein displacement is irrelevant); fluoxetine does not significantly alter renal lithium clearance; omeprazole does not cause clinically meaningful urinary alkalinisation sufficient to trap lithium.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.