A patient with central diabetes insipidus taking oral desmopressin 0.2 mg twice daily plus 0.1 mg at night now has new‑onset polydipsia, increased fluid intake, and salt cravings—what is the most likely cause and how should the desmopressin dose be adjusted?

Desmopressin Overdose with Water Intoxication

The most likely cause is desmopressin overdose leading to water intoxication and dilutional hyponatremia; immediately reduce the total daily dose to 0.2–0.3 mg/day and implement scheduled drug-free periods to allow breakthrough diuresis. 1

Pathophysiology of the Clinical Picture

• Polydipsia and salt cravings are physiologic responses to dilutional hyponatremia caused by excessive antidiuretic coverage that eliminates breakthrough diuresis in central diabetes insipidus. 1
• The current regimen of 0.5 mg/day (0.2 mg twice daily plus 0.1 mg at night) creates continuous 24-hour antidiuretic coverage, preventing the necessary periods of free water excretion. 1
• Chronic water retention develops when desmopressin dosing eliminates breakthrough diuresis, leading to mild-to-moderate hyponatremia that triggers compensatory salt cravings. 1

Immediate Diagnostic Steps

• Check serum sodium urgently—a low-normal value (135–138 mmol/L) or frankly low (<135 mmol/L) confirms desmopressin-induced water retention. 1
• Measure plasma osmolality; an inappropriately low value relative to the clinical picture supports the diagnosis. 1
• In central diabetes insipidus, serum sodium is normally maintained at steady state, so any deviation below 138 mmol/L indicates possible overdosing. 1

Dose Adjustment Protocol

Reduce Total Daily Dose

• Decrease desmopressin to 0.2–0.3 mg/day total, split into two doses (e.g., 0.1 mg morning and 0.1–0.2 mg evening), which fits within the standard therapeutic range of 0.2–0.4 mg/day for most central diabetes insipidus patients. 1, 2
• The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover. 2

Implement Scheduled Drug Holidays

• Omit the nighttime dose and skip one morning or evening dose 1–2 times per week to allow breakthrough diuresis and prevent fluid intoxication. 1
• Planned desmopressin-free periods are essential to excrete accumulated free water. 1

Optimize Dosing Intervals

• Separate morning and evening doses by at least 8–12 hours; given desmopressin's terminal half-life of approximately 2.8 hours, this creates natural nadirs in antidiuretic effect. 1
• Administer oral tablets at least 1 hour before sleep, as maximum renal concentrating effect occurs after 1–2 hours. 3

Fluid Management Strategy

• Limit evening fluid intake to ≤200 mL and avoid drinking after the last dose until the following morning. 3, 1
• Allow unrestricted fluid intake during drug-free (breakthrough) periods to permit adequate diuresis. 1
• Polydipsia in the context of desmopressin overdose is a contraindication to further dosing and requires dose reduction, not dose escalation. 3, 1

Monitoring Plan

• Re-check serum sodium within 1 week of dose adjustment, then at 1 month and periodically thereafter to confirm correction. 1
• Intermittently track urine volume to verify adequate breakthrough diuresis is occurring. 1
• Monitor for resolution of salt cravings as hyponatremia corrects. 1

Critical Pitfall to Avoid

• Do not increase desmopressin in response to polydipsia—this is a recognized pitfall that exacerbates hyponatremia and water intoxication. 1
• The major complication of desmopressin therapy is water intoxication and hyponatremia, which can lead to seizures if unrecognized. 4
• Never maintain 24-hour antidiuretic coverage without planned breaks. 1