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Lithium-Induced NDI — MRCPsych Paper B MCQ

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HardMood DisordersLithium-Induced NDIMRCPsych Paper B

A 36-year-old woman with schizoaffective disorder develops marked polyuria and polydipsia during long-term treatment with lithium and olanzapine. On admission, her serum sodium is 152 mmol/L, serum lithium is 0.8 mmol/L and urine osmolality is 120 mOsm/kg. After controlled free-water replacement, her serum sodium normalises. Urine osmolality increases only minimally following desmopressin, confirming lithium-induced nephrogenic diabetes insipidus. Her eGFR and serum potassium are normal. Previous attempts to replace lithium caused severe affective relapse, so the multidisciplinary team decides to continue it with enhanced monitoring. Which pharmacological adjunct most specifically targets the lithium-dependent renal mechanism causing her persistent polyuria?

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Correct answer: A — Amiloride

Amiloride is the best answer. Lithium enters collecting-duct principal cells through epithelial sodium channels (ENaC), impairing aquaporin-2 expression and producing renal resistance to vasopressin. Amiloride blocks ENaC and therefore directly reduces intracellular lithium exposure. Thiazides can paradoxically reduce urine volume and remain a treatment option, but they do not target lithium entry and may appreciably increase lithium concentrations. Desmopressin is principally used for central diabetes insipidus; the minimal response here confirms renal vasopressin resistance, although occasional partial responses can occur. Furosemide does not treat this mechanism and may worsen water and electrolyte loss. Carbamazepine is not an established treatment for lithium-induced nephrogenic diabetes insipidus. Amiloride use is off-label and requires specialist supervision with monitoring of potassium, renal function and lithium concentration.

Reference: Schoot TS, et al. ENaC inhibitors for the management of lithium related polyuria: a systematic review. 2025. https://pubmed.ncbi.nlm.nih.gov/18596116/