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

Medications for Nocturnal Enuresis (Bedwetting)

Desmopressin is the first-line pharmacological treatment for nocturnal enuresis, with oral tablets (0.2-0.4 mg) taken 1 hour before bedtime being the preferred formulation. 1, 2

Primary Medication: Desmopressin

Mechanism and Efficacy

• Desmopressin is a synthetic analogue of antidiuretic hormone (vasopressin) that reduces nighttime urine production 1
• Effectiveness ranges from 10-65%, with approximately 30% achieving complete response and 40% partial response 1, 2, 3
• The anti-enuretic effect appears immediately once treatment begins 1
• Relapse rates after discontinuation can be as high as 80% 1

Dosing Specifications

• Oral tablets: 0.2-0.4 mg taken at least 1 hour before sleep 1, 2
• Oral melt tablets (lyophilisate): 120-240 μg taken 30-60 minutes before bedtime 1, 2
• Dosing is not influenced by body weight or age 1, 2
• Start with either the higher dose and taper down if effective, or begin low and titrate up 1

Critical Safety Requirements

• Fluid restriction is mandatory: Evening intake must be limited to 200 ml (6 ounces) or less with no drinking until morning 1, 2, 3
• Polydipsia (excessive thirst/drinking) is an absolute contraindication 1, 2
• Water intoxication with hyponatremia and convulsions can occur if combined with excessive fluid intake 1, 2
• Avoid nasal spray formulations due to higher risk of hyponatremia; oral formulations are strongly preferred 1, 2
• Schedule regular short drug holidays to assess whether medication is still needed 1, 2
• Monitor electrolytes if intercurrent illness occurs during treatment 1

Best Candidates for Desmopressin

• Children with documented nocturnal polyuria (nighttime urine production >130% of expected bladder capacity) 1
• Patients with normal bladder reservoir function (maximum voided volume >70% of expected bladder capacity) 1
• Cases where alarm therapy has failed or is unlikely to be complied with 1

Second-Line Medication: Imipramine

When to Use

• Reserve for cases where desmopressin fails or is not feasible 1
• Consider as third-line therapy at tertiary care facilities due to safety concerns 3

Dosing and Efficacy

• Dose: 1.0-2.5 mg/kg per day (typically 25-75 mg) as a single bedtime dose 1, 4
• For children aged 6+: Start with 25 mg one hour before bedtime 4
• If no response in one week: Increase to 50 mg for children under 12 years, or up to 75 mg for children over 12 4
• Maximum dose should not exceed 2.5 mg/kg/day 4
• Effectiveness: 40-60% response rate 1
• Relapse rate is high (up to 50%) 1

Safety Monitoring

• Obtain pretreatment electrocardiogram to detect underlying rhythm disorders due to risk of cardiac arrhythmia 1
• The mechanism of action for enuresis remains poorly understood and is not related to its antidepressant effects 1
• Major hazard: Accidental ingestion by younger siblings can be fatal 1

Third-Line: Anticholinergic Medications

Indications

• Use only when standard treatments (desmopressin, alarm therapy) have failed 1
• Particularly indicated if there is evidence of detrusor overactivity 1, 3
• Approximately 40% of treatment-resistant children respond to anticholinergics 1

Prerequisites Before Starting

• Establish regular voiding habits first (non-pharmacological approach) 1
• Exclude or treat constipation 1
• Exclude post-void residual urine, dysfunctional voiding, or low voiding frequency 1
• Complete frequency-volume chart and perform uroflowmetry with ultrasound measurement of post-void residual 1

Medication Options and Dosing

• Tolterodine: 2 mg at bedtime (may double if needed) 1, 3
• Oxybutynin: 5 mg at bedtime (may double if needed) 1, 3
• Propiverine: 0.4 mg/kg at bedtime (may double if needed) 1, 3
• Anti-enuretic effect should appear within maximum of 2 months, often earlier 1
• Often requires combination with desmopressin at standard dose 1

Side Effects and Monitoring

• Most bothersome: Constipation, which may herald decreasing effectiveness 1
• Greatest danger: Post-void residual urine causing urinary tract infections 1
• Risk of mood changes 1
• Child must maintain sound voiding habits and family must watch for dysuria or unexplained fever 1

Combination Therapy for Refractory Cases

Desmopressin + Imipramine

• This combination is superior to desmopressin + oxybutynin for treatment-resistant cases 5
• Complete response rate: 68% vs 5% (desmopressin + imipramine vs desmopressin + oxybutynin) 5
• The odds ratio for success is 42.5 times greater with imipramine combination 5
• Imipramine's central mechanism (rather than anticholinergic properties) likely explains superiority 5

Desmopressin + Anticholinergic

• The combination of desmopressin with sustained-release anticholinergic may be more effective than desmopressin alone 1
• Use low-dose imipramine (25 mg) combined with solifenacin (5-10 mg) for desmopressin-refractory cases 6

Treatment Algorithm

1. Rule out underlying conditions: Urinary tract infections, diabetes, constipation, neurologic abnormalities 1, 3
2. Implement behavioral interventions first: Fluid management, regular voiding schedules, reward systems 3, 7
3. For children 6+ years requiring medication: Start desmopressin 0.2-0.4 mg orally 1 hour before bedtime with strict fluid restriction 1, 2
4. If desmopressin fails after 2-3 months: Consider imipramine 1.0-2.5 mg/kg at bedtime (with ECG monitoring) 1, 4
5. For treatment-resistant cases: Add anticholinergic to desmopressin OR switch to desmopressin + imipramine combination 1, 5
6. If detrusor overactivity suspected: Anticholinergics become more appropriate as adjunct therapy 1, 3

Critical Pitfalls to Avoid

• Never use desmopressin nasal spray due to higher hyponatremia risk 1, 2
• Never allow fluid intake >200 ml in evening during desmopressin treatment 1, 2
• Never prescribe imipramine without baseline ECG 1
• Never start anticholinergics without first addressing constipation and establishing regular voiding habits 1
• Never punish or shame children for bedwetting, as this worsens outcomes 1, 3, 7
• Never forget that alarm therapy (not medications) has the best long-term success rates with lower relapse 1, 8