What is the recommended treatment for nocturnal enuresis in pediatric patients?

Treatment of Nocturnal Enuresis in Pediatric Patients

For children 6 years and older with primary nocturnal enuresis, enuresis alarm therapy is the first-line treatment, achieving approximately 66% initial success with sustained long-term benefits, while desmopressin (0.2-0.4 mg oral formulation) serves as first-line pharmacological therapy for children with documented nocturnal polyuria or when alarm therapy fails. 1, 2

Initial Assessment Requirements

Before initiating any treatment, complete the following mandatory evaluations:

• Urinalysis to exclude diabetes mellitus, urinary tract infection, or kidney disease 1, 2
• Frequency-volume chart or bladder diary for at least 1-2 days (some guidelines recommend 1 week) to document nocturnal polyuria and distinguish monosymptomatic from non-monosymptomatic enuresis 3, 1
• Constipation screening by assessing bowel movement frequency and stool consistency, as treating constipation alone resolves urinary symptoms in up to 63% of cases 1, 2
• Early-morning urine specific gravity (values <1.015 may indicate ADH deficiency) 1

Treatment Algorithm by Age and Clinical Presentation

Children Under 6 Years Old

Start with behavioral interventions only:

• Reward system (sticker chart) for dry nights to increase motivation 1, 2
• Regular daytime voiding schedule (morning, at least twice during school, after school, dinner time, and bedtime) 1, 2
• Evening fluid restriction to 200 ml (6 ounces) or less 1
• Aggressive constipation treatment with dietary changes and polyethylene glycol if needed, as this alone may resolve enuresis 1, 2

Children 6 Years and Older

First-Line Treatment: Enuresis Alarm Therapy

• Enuresis alarms achieve approximately 66% initial success rate with more than half experiencing long-term success after treatment stops 1, 4
• Provide written instructions, establish a contract, and schedule frequent monitoring appointments to enhance success 2
• Continue treatment for at least 2-3 months before attempting to wean 2
• Alarms produce more sustained benefits than desmopressin, with evidence showing lower failure and relapse rates after treatment discontinuation 4

First-Line Pharmacological Treatment: Desmopressin

Optimal candidates for desmopressin:

• Children with nocturnal polyuria (nighttime urine production >130% of expected bladder capacity for age) and normal bladder function (maximum voided volume >70% of expected bladder capacity) 3
• Children in whom alarm therapy has failed or is unlikely to be successful 3, 1

Dosing and administration:

• Oral dose: 0.2-0.4 mg tablets or 120-240 mg melt formulation 1, 2
• Administer at least 1 hour before bedtime (maximum renal concentrating effect occurs 1-2 hours after administration) 3, 1
• Dose is not influenced by body weight or age 3

Critical safety requirements (MANDATORY):

• Fluid restriction of 200 ml (6 ounces) or less in the evening, with no drinking until morning to prevent water intoxication with hyponatremia 3, 1, 2
• Polydipsia (excessive thirst/drinking) is an absolute contraindication for desmopressin 3
• Strongly avoid nasal spray formulations due to higher risk of water intoxication with hyponatremia and convulsions; oral formulations are strongly preferred 3

Expected outcomes:

• Approximately 30% become full responders (completely dry) during treatment 3, 2
• 40% achieve partial response (significant reduction in wet nights) 3, 2
• Desmopressin reduces bedwetting by at least one night per week during treatment compared to placebo 4
• Effect is immediate, allowing families to quickly determine ongoing necessity 3

Monitoring:

• Schedule regular short drug holidays to assess whether medication is still needed 3
• Monthly follow-up appointments to sustain motivation and assess treatment response 1, 2

Second-Line Treatment for Resistant Cases

Combination Therapy with Anticholinergics

If standard desmopressin treatment fails and there is evidence of detrusor overactivity:

• Add anticholinergics such as tolterodine (2 mg), oxybutynin (5 mg), or propiverine (0.4 mg/kg) at bedtime 3, 2
• Approximately 40% of treatment-resistant children respond to this combination 3, 2
• Monitor for constipation and post-void residual urine that may cause UTIs 2

Combination of Alarm Therapy with Desmopressin

• Combining alarm therapy with desmopressin may benefit children not responding to single modalities 2
• Evidence suggests alarm treatment supplemented by desmopressin results in fewer wet nights during treatment, though data on long-term failure and relapse rates remain inconclusive 4

Alternative Combination for Desmopressin-Resistant Nocturnal Polyuria

• Morning furosemide (0.5 mg/kg) plus desmopressin may benefit patients with desmopressin-resistant nocturnal polyuria, with 9 of 12 resistant patients achieving continence in one pilot study 3

Third-Line Treatment: Imipramine

Consider imipramine only as third-line therapy at tertiary care facilities due to safety concerns: 2

• Approximately 50% of children with therapy-resistant enuresis respond to imipramine 2
• FDA-approved dosing for childhood enuresis (ages 6 and older): 5
  • Initial dose: 25 mg/day given one hour before bedtime 5
  • If no response within one week, increase to 50 mg nightly in children under 12 years; children over 12 may receive up to 75 mg nightly 5
  • Maximum dose: 2.5 mg/kg/day should not be exceeded 5
  • For early night bedwetters, divided dosing (25 mg in mid-afternoon, repeated at bedtime) may be more effective 5
• Low-dose imipramine (5 mg) combined with desmopressin showed significantly better recovery (83.3%) compared to desmopressin alone (29.4%) in desmopressin non-responders 6
• Taper gradually rather than abruptly discontinue to reduce relapse tendency 5

Critical Pitfalls to Avoid

• Never use nasal spray desmopressin formulation due to higher risk of hyponatremia 3
• Inadequate fluid restriction counseling can lead to water intoxication; families must understand the strict 200 ml evening limit 3, 1
• Not screening for polydipsia is a critical mistake, as it is an absolute contraindication for desmopressin 3
• Continuing desmopressin indefinitely without drug holidays prevents assessment of ongoing need 3
• Punishing, shaming, or creating control struggles worsens the condition and creates psychological distress 1, 2
• Expecting cure rather than symptom control with desmopressin leads to disappointment, as the curative potential is low 3
• Not treating constipation first when present, as this alone may resolve enuresis in up to 63% of cases 1, 2

When to Refer to Pediatric Urology

Immediate referral is necessary for: 1

• Severe or continuous incontinence
• Weak urinary stream
• Non-monosymptomatic enuresis
• Recurrent urinary tract infections
• Suspected urinary tract malformations
• No improvement after 1-2 months of consistent therapy 1, 2

Family Education

• Educate parents that 15-20% of 5-year-olds have enuresis with a 14% spontaneous remission rate per year to emphasize the nonvolitional nature and prevent punitive responses 1, 2
• Reassure families that not all children require active treatment and many parents choose watchful waiting after ruling out underlying conditions 1