In a patient with central diabetes insipidus receiving desmopressin 0.2 mg twice daily and 0.1 mg at night who now reports new‑onset polydipsia, increased fluid intake, and salt cravings, what are the likely causes and how should this be managed?

Likely Cause: Desmopressin Overdosing Leading to Polydipsia

This patient is experiencing paradoxical polydipsia and salt cravings due to excessive desmopressin dosing (0.5 mg/day total), which is preventing adequate breakthrough diuresis and causing chronic mild hyponatremia—the treatment is to reduce the total daily dose and implement mandatory drug-free periods to allow water excretion. 1, 2

Understanding the Mechanism

The current regimen of 0.2 mg twice daily plus 0.1 mg at night (total 0.5 mg/day) is providing near-continuous antidiuretic coverage without allowing periods of breakthrough diuresis. 1 This prevents the excretion of accumulated free water, leading to:

• Chronic water retention despite normal or low-normal serum sodium 2, 3
• Compensatory thirst mechanism activation as the body attempts to maintain osmotic balance 4
• Salt cravings as a physiologic response to relative hyponatremia or dilutional effects 5

The FDA label explicitly warns that desmopressin can cause fluid retention and hyponatremia, particularly when patients lack adequate drug-free periods. 2

Immediate Diagnostic Steps

Check serum sodium and plasma osmolality immediately to confirm hyponatremia (even mild hyponatremia <135 mmol/L can trigger these symptoms). 2, 6 The 2025 expert consensus emphasizes that patients with CDI typically maintain normal serum sodium at steady state with free water access, so any deviation suggests dosing issues. 5

Key laboratory findings to expect:

• Serum sodium may be low-normal (135-138 mmol/L) or frankly low (<135 mmol/L) 6
• Plasma osmolality inappropriately low for the clinical picture 5
• Urine osmolality persistently elevated without breakthrough periods 7

Treatment Algorithm

Step 1: Reduce Total Daily Dose

Decrease the total daily desmopressin to 0.2-0.3 mg/day maximum (split into 2 doses), as the current 0.5 mg/day exceeds typical therapeutic needs. 5, 8 The standard dose range is 0.2-0.4 mg/day for most patients with central DI. 5, 8

Step 2: Implement Mandatory Drug Holidays

Institute planned desmopressin-free periods to allow breakthrough diuresis and water excretion. 1 The 2025 Praxis guidelines specifically state that patients with central DI "can and should take periodic breaks from desmopressin to prevent water intoxication and hyponatremia." 1

Practical implementation:

• Skip the nighttime 0.1 mg dose entirely 1
• Consider skipping one morning or evening dose 1-2 times weekly 1
• Monitor for polyuria during these breaks (this is therapeutic, not a treatment failure) 1

Step 3: Adjust Dosing Schedule

Separate morning and evening doses by at least 8-12 hours to create natural nadirs in antidiuretic effect. 1, 2 The terminal half-life of desmopressin is only 2.8 hours, so spacing doses allows physiologic breakthrough. 2

Step 4: Implement Strict Fluid Management

Paradoxically, this patient needs unrestricted fluid access during breakthrough periods to safely excrete accumulated water. 5, 1 However, during periods of desmopressin coverage, limit evening fluid intake to 200 mL or less with no drinking until morning. 5, 9, 8

Monitoring Requirements

• Recheck serum sodium within 1 week of dose adjustment 2
• Monitor at 1 month and periodically thereafter 2
• Track urine volume intermittently to ensure adequate breakthrough diuresis is occurring 1
• Assess symptom resolution (decreased thirst and salt cravings should improve within days) 4

Critical Pitfall to Avoid

Do not interpret the polydipsia as "inadequate treatment" requiring more desmopressin—this is the most dangerous error. 5, 9 Polydipsia is an absolute contraindication to desmopressin therapy when it represents primary polydipsia, but in this case it is iatrogenic from overdosing. 5, 9, 2 The FDA label explicitly states that "polydipsia is a contraindication" and that "use of desmopressin without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia." 2

Why This Regimen Failed

The dose conversion from intranasal to oral desmopressin shows wide inter-individual variation (ratios of 1:10 to 1:31), 7, 10 and this patient's regimen may have been over-converted. Studies show that oral desmopressin actually has lower rates of hyponatremia than intranasal formulations when properly dosed (7.6% vs 11.7% incidence). 6

Expected Outcome

With dose reduction and implementation of drug holidays, symptoms should resolve within 1-2 weeks as water balance normalizes. 1, 6 The patient should experience decreased thirst, resolution of salt cravings, and return to baseline fluid intake patterns while maintaining adequate control of diabetes insipidus. 5, 7