What medications are used to treat nocturnal enuresis (bedwetting)?

Medications for Nocturnal Enuresis (Bedwetting)

Two medications have proven efficacy for treating bedwetting: desmopressin (DDAVP) and imipramine, with desmopressin being the preferred first-line pharmacological option due to its superior safety profile, though behavioral alarm therapy remains the most effective long-term treatment. 1

First-Line Pharmacological Treatment: Desmopressin

Desmopressin is the primary medication for bedwetting when alarm therapy has failed or is not feasible. 2, 3

Mechanism and Efficacy

• Desmopressin is a synthetic analogue of antidiuretic hormone (vasopressin) that reduces nighttime urine production by acting on renal collecting ducts 1
• Approximately 30% of children achieve complete dryness (full response) and 40% achieve partial response during active treatment 2
• The effect is immediate, allowing families to quickly assess whether the medication is working 2
• However, relapse rates after stopping treatment are high (up to 80%), meaning desmopressin primarily provides symptom control rather than cure 1

Optimal Candidates

• Children with nocturnal polyuria (nighttime urine production >130% of expected bladder capacity for age) and normal bladder function respond best 2
• Children in whom alarm therapy has failed are appropriate candidates 2
• First-morning urine specific gravity may help predict who will respond to desmopressin 1

Dosing and Administration

• Oral tablets: 0.2 to 0.4 mg taken at least 1 hour before sleep 2, 3
• The dose is not influenced by body weight or age 2
• Start with 0.2 mg (one tablet) and increase incrementally to two or three tablets if the lower dose proves ineffective 1
• The maximum renal concentrating effect occurs 1-2 hours after administration 2
• Oral formulations are strongly preferred over nasal spray due to safety concerns 2

Critical Safety Requirements

Fluid restriction is mandatory to prevent life-threatening water intoxication and hyponatremia. 2, 3

• Limit evening fluid intake to 200 ml (6 ounces) or less, with no drinking from the time of administration until the following morning 2, 3
• Polydipsia (excessive thirst/drinking) is an absolute contraindication for desmopressin 2
• Nasal spray formulations are strongly discouraged due to higher risk of water intoxication with hyponatremia and convulsions 2
• Although water intoxication is rare, serious cases including seizures and coma have been reported, particularly when fluid restriction is not followed 1, 4
• Serum electrolyte monitoring should be performed if intercurrent illness complicates treatment 1

Treatment Duration

• Regular short drug holidays are recommended to assess whether medication is still needed 2
• Continue effective treatment for 4 to 6 months before attempting to wean 1

Second-Line Pharmacological Treatment: Imipramine

Imipramine should be reserved as second- or third-line therapy due to safety concerns, particularly the risk of cardiac arrhythmia. 1, 3

Efficacy and Mechanism

• Imipramine demonstrates 40% to 60% effectiveness in reducing bedwetting 1
• The relapse rate is high (up to 50%) after discontinuation 1
• The mechanism of action for enuresis remains poorly understood and is not conclusively related to blood level 1

Dosing and Administration

• Bedtime dose: 1.0 to 2.5 mg/kg (typically 25-75 mg depending on age) 1
• For children aged 6 and older, start with 25 mg 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
• A daily dose greater than 75 mg does not enhance efficacy and increases side effects 5
• A dose of 2.5 mg/kg/day should not be exceeded 5

Safety Monitoring

• A pretreatment electrocardiogram should be obtained to detect underlying rhythm disorders due to the risk of cardiac arrhythmia with tricyclic antidepressants 1
• This precaution is warranted even though the enuresis dose is lower than the antidepressant dose 1
• The most serious problem is accidental ingestion by younger siblings, which can be fatal 1

When to Use

• Consider imipramine when alarm therapy and desmopressin have failed or are not feasible 1
• Approximately 50% of children with therapy-resistant enuresis respond to imipramine 3

Anticholinergic Medications (Second-Line or Adjunctive)

Anticholinergics are reserved for children with suspected detrusor overactivity or as combination therapy when standard treatments fail. 3, 6

Available Options and Dosing

• Oxybutynin: 5 mg at bedtime 3
• Tolterodine: 2 mg at bedtime 3
• Propiverine: 0.4 mg/kg at bedtime 3

When to Use

• Consider when there is a history of urgency, frequency, daytime wetting, or urinary tract infections suggesting bladder dysfunction 7
• Anticholinergics alone are less effective than alarm therapy for achieving 14 consecutive dry nights 6

Monitoring

• Monitor for constipation and post-void residual urine that may cause urinary tract infections 3

Combination Therapy for Treatment-Resistant Cases

Combining medications or adding medications to alarm therapy can improve outcomes in children who fail monotherapy. 2, 6

Desmopressin Plus Anticholinergics

• Approximately 40% of treatment-resistant children respond to combination therapy with desmopressin plus anticholinergics (tolterodine, oxybutynin, or propiverine) 2
• This combination is particularly effective when there is evidence of detrusor overactivity 2

Imipramine Plus Anticholinergics

• Combination therapy with imipramine and oxybutynin is more effective than imipramine monotherapy (68% vs. monotherapy) 6
• This combination also has significantly lower relapse rates than imipramine alone 6

Alarm Plus Desmopressin

• Combining alarm therapy with desmopressin may be beneficial for children not responding to single modalities 3, 8
• This combination probably reduces the number of wet nights at the end of treatment compared to alarm alone 8

Comparative Effectiveness: Medications vs. Alarm Therapy

Alarm therapy produces superior long-term outcomes compared to medications and should be considered first-line treatment when families are cooperative and motivated. 1

• Alarm therapy achieves approximately 66% success rate with better sustained outcomes after treatment stops 3
• Bedwetting alarms are more effective than medications (including oxybutynin and amphetamine) in achieving 14 consecutive dry nights 6
• Desmopressin is inferior to conditioning alarms as primary therapy for long-term cure 9
• However, medications provide faster initial response and are appropriate when alarm therapy fails or is not feasible 1

Essential Pre-Treatment Assessment

Before initiating medication, complete the following:

• Urinalysis (mandatory) to rule out glycosuria, proteinuria, and urinary tract infection 1, 3
• Frequency-volume chart for at least 2 days to document nocturnal polyuria 2
• Assessment for constipation, as treating it can resolve enuresis in up to 63% of cases 3
• Evaluation for sleep apnea if snoring or enlarged tonsils/adenoids are present, as surgical correction may cure enuresis 1

Critical Pitfalls to Avoid

• Never use desmopressin nasal spray due to higher risk of hyponatremia 2
• Never prescribe desmopressin without explicit instructions about the 200 ml evening fluid limit 2, 3
• Never prescribe desmopressin to children with polydipsia (absolute contraindication) 2
• Never continue desmopressin indefinitely without drug holidays to assess ongoing need 2
• Never prescribe imipramine without obtaining a baseline ECG due to cardiac arrhythmia risk 1
• Never overlook constipation, as it must be treated first before escalating urinary treatments 1, 3
• Never punish children for bedwetting, as this worsens the situation and creates psychological distress 1, 3