Patient with known diabetes insipidus on desmopressin 0.2 mg twice daily and 0.1 mg at night now has increased thirst and salt cravings; what should be done?

Desmopressin Overdose: Immediate Dose Reduction Required

Your patient is experiencing desmopressin overdose manifested by salt cravings and increased thirst—you must reduce the total daily dose to 0.2–0.3 mg/day and implement scheduled drug-free periods to allow breakthrough diuresis. 1

Understanding the Clinical Picture

Your patient's symptoms represent a classic presentation of desmopressin-induced water retention:

• Salt cravings are a physiologic response to dilutional hyponatremia caused by excessive antidiuretic coverage in central diabetes insipidus 1
• The current regimen (0.2 mg twice daily + 0.1 mg at night = 0.5 mg/day total) exceeds the standard therapeutic range of 0.2–0.4 mg/day and eliminates breakthrough diuresis, leading to chronic water retention 1
• Increased thirst in the context of desmopressin therapy is a contraindication to further dosing, not an indication to increase the dose—this is a critical pitfall to avoid 1, 2

Immediate Diagnostic Steps

Before adjusting therapy, obtain:

• Serum sodium level (expect low-normal 135–138 mmol/L or frankly low <135 mmol/L) 1
• Serum osmolality (inappropriately low relative to clinical picture supports desmopressin-induced water retention) 1
• Urine osmolality to assess current antidiuretic effect 3

Therapeutic Algorithm

Step 1: Reduce Total Daily Dose

Decrease desmopressin to 0.2–0.3 mg/day total, split into two doses separated by at least 8–12 hours 1:

• Example: 0.1 mg in morning + 0.1 mg in evening, OR
• 0.2 mg in morning + 0.1 mg in evening (maximum 0.3 mg/day)
• The 8–12 hour separation creates natural nadirs in antidiuretic effect given desmopressin's terminal half-life of ~2.8 hours 1

Step 2: Implement Scheduled Drug Holidays

Omit desmopressin 1–2 times per week to allow breakthrough diuresis and prevent fluid intoxication 1:

• Skip the nighttime dose AND one morning or evening dose on designated days
• During drug-free periods, allow unrestricted fluid intake 1
• This prevents the continuous 24-hour antidiuretic coverage that causes water intoxication 1

Step 3: Strict Evening Fluid Restriction

Limit evening fluid intake to ≤200 mL (6 ounces) with no drinking after the last dose until the following morning 1, 2, 4:

• This is mandatory to prevent water intoxication with hyponatremia and seizures 2, 4
• Applies only on days when desmopressin is administered 1

Step 4: Adjust Morning and Evening Doses Separately

Titrate each dose independently to establish proper diurnal rhythm of water turnover 3:

• Goal: adequate sleep duration without nocturia
• Goal: appropriate (not excessive) water turnover during waking hours 3

Monitoring Protocol

• Recheck serum sodium within 1 week of dose adjustment 1, 2
• Repeat at 1 month, then periodically thereafter 1, 2
• Intermittently track urine volume to verify adequate breakthrough diuresis 1
• Monitor for resolution of salt cravings as hyponatremia corrects 1

Critical Safety Warnings

Do NOT Increase Desmopressin

Never increase desmopressin in response to polydipsia—this is a recognized pitfall that exacerbates hyponatremia 1:

• Polydipsia in the context of desmopressin therapy indicates overdose, not underdose 1, 2
• Increasing the dose will worsen water retention and hyponatremia 1

Maintain Free Water Access

Patients with diabetes insipidus must have free access to fluid 24/7 except during evening restriction periods 2:

• Restricting water access is a life-threatening error leading to severe hypernatremic dehydration 2
• This applies during breakthrough diuresis periods when desmopressin is omitted 1

Recognize Hyponatremia Risk

Water intoxication with hyponatremia and seizures is the major complication of desmopressin therapy 2, 4:

• Occurs when continuous dosing eliminates breakthrough diuresis 1
• Patients with polydipsia are at particularly high risk 4
• Failure to restrict evening fluids dramatically increases this risk 2, 4

Special Consideration: Central vs. Nephrogenic DI

This management applies only to central diabetes insipidus where desmopressin is effective 1:

• If this patient has nephrogenic DI, desmopressin is completely inappropriate and should be discontinued 5, 1
• Nephrogenic DI does not respond to desmopressin at any dose 5, 1
• Consider genetic testing if diagnosis is uncertain 5

Expected Outcome

With appropriate dose reduction and drug holidays:

• Salt cravings should resolve as serum sodium normalizes 1
• Thirst will return to baseline 1
• Patient will experience controlled breakthrough diuresis during drug-free periods 1
• Risk of hyponatremia and water intoxication will be eliminated 1, 2