What is the recommended dosage and treatment plan for desmopressin (synthetic analogue of vasopressin) in pediatric and adult patients with nocturnal enuresis, particularly those with a history of nocturnal polyuria?

Desmopressin for Nocturnal Enuresis

Recommended Dosing

Start with oral desmopressin 0.2-0.4 mg tablets taken at least 1 hour before sleep, or 120-240 μg oral melt tablets taken 30-60 minutes before bedtime, with mandatory fluid restriction to 200 mL or less in the evening. 1, 2

Dosing Strategy

• The dose is not influenced by body weight or age - you can either start with the higher dose and taper down, or begin low and titrate up based on response 1
• The maximum renal concentrating effect occurs 1-2 hours after administration 2
• Oral formulations (tablets or lyophilizate) are strongly preferred over nasal spray due to significantly higher risk of water intoxication with hyponatremia and convulsions with the nasal formulation 2, 1

Dose Titration Approach

• If starting at 0.2 mg, you can increase in 0.2 mg increments at 2-week intervals until the patient is completely dry or reaches the maximum dose of 0.6 mg 3
• A linear dose-response relationship exists, with 27%, 30%, and 40% reduction in wet nights at 0.2,0.4, and 0.6 mg doses respectively 3
• However, 44% of patients achieve at least 50% reduction in wet nights at the lower doses of 0.2-0.4 mg, so aggressive titration is not always necessary 3

Patient Selection

Desmopressin works best in children with documented nocturnal polyuria (nighttime urine production >130% of expected bladder capacity for age) and normal bladder reservoir function (maximum voided volume >70% of expected bladder capacity for age). 4, 2

Ideal Candidates

• Children with nocturnal polyuria documented on frequency-volume chart 4
• Patients in whom alarm therapy has failed or who refuse alarm treatment 4, 2
• Children age 6 years or older (active treatment should not usually be started before age 6) 4
• Adults with nocturnal enuresis associated with nocturnal polyuria (effectiveness rates 10-65%) 5

Absolute Contraindications

• Polydipsia (excessive thirst/drinking) is an absolute contraindication - these patients cannot safely restrict fluids 1, 2, 5
• Severe renal impairment (CrCl <30 mL/min) 1

Mandatory Safety Requirements

Fluid restriction is absolutely essential to prevent life-threatening water intoxication with hyponatremia and seizures - limit evening fluid intake to 200 mL (6 ounces) or less, with no drinking from 1 hour before the dose until morning. 1, 2, 5

Pre-Treatment Evaluation

• Perform urine dipstick to rule out glycosuria and proteinuria 1, 2
• Complete frequency-volume chart for at least 2 days to document nocturnal polyuria and assess bladder capacity 4, 1, 2
• Screen for polydipsia - ask specifically about excessive thirst and drinking patterns 1, 2
• Assess for and treat constipation before starting therapy 4

Ongoing Monitoring

• Regular short drug holidays are mandatory to assess whether medication is still needed 1, 2
• The effect is immediate, so families can quickly determine if ongoing treatment is necessary 2
• Monitor for signs of hyponatremia: headache, nausea, insomnia 6

Expected Outcomes

Approximately 30% of children become full responders (completely dry) and 40% achieve partial response during active treatment, with an overall 30-40% reduction in wet nights. 4, 1, 2

Realistic Expectations

• The curative potential is low - desmopressin provides symptom control rather than cure 4, 2
• Relapse rates are high after discontinuation 7
• Response is variable due to different underlying pathophysiological mechanisms 7, 8
• 20-60% of children are desmopressin-resistant, possibly due to disturbances in intrinsic renal circadian clock systems beyond vasopressin 8

Treatment Algorithm for Therapy-Resistant Cases

If Desmopressin Fails as Monotherapy

1. Verify compliance with fluid restriction - inadequate restriction is a common cause of treatment failure 2
2. Ensure correct timing and dosing - confirm the medication is taken 1 hour before sleep with proper dose 1, 2
3. Try the alternative first-line therapy - switch to enuresis alarm if not previously attempted 4
4. Consider combination therapy - add anticholinergics (tolterodine, oxybutynin, or propiverine) if detrusor overactivity is present, with approximately 40% of treatment-resistant patients responding 2
5. For desmopressin-resistant nocturnal polyuria - consider morning furosemide (0.5 mg/kg) plus desmopressin to shift sodium and osmotic excretion to daytime 2

Common Pitfalls to Avoid

• Using nasal spray formulation - this carries significantly higher risk of hyponatremia and is strongly discouraged 2, 1
• Inadequate fluid restriction counseling - families must understand the strict 200 mL evening limit to prevent water intoxication 2, 1
• Continuing indefinitely without drug holidays - prevents assessment of ongoing need 1, 2
• Not screening for polydipsia - this is a critical contraindication that must be identified before starting treatment 1, 2
• Expecting cure rather than symptom control - set realistic expectations about the low curative potential 4, 2
• Ignoring food effects - oral bioavailability is significantly affected by food, so timing relative to meals matters 7

Safety Profile

Desmopressin is generally well tolerated when used correctly 3, 6. Most adverse events are mild to moderate and include:

• Headache, nausea, diarrhea, abdominal pain, dry mouth 6
• Rhinitis, pharyngitis, increased cough 3
• Clinically significant hyponatremia occurs in approximately 5% of patients and requires withdrawal in ≤3% 9
• Most adverse events are transient and resolve before treatment completion 3