What is the drug of choice for treating nocturnal (nighttime) enuresis in adults?

Drug of Choice for Nocturnal Enuresis in Adults

Desmopressin is the drug of choice for treating nocturnal enuresis in adults, particularly when associated with nocturnal polyuria. 1, 2, 3

Mechanism and Efficacy

• Desmopressin is a synthetic analogue of antidiuretic hormone (vasopressin) that decreases nighttime urine production 1, 3
• In adults with nocturia associated with nocturnal polyuria, desmopressin significantly reduces the mean number of nocturnal voids and normalizes the rate of nocturnal urine production 3
• Desmopressin increases the initial sleep period or mean maximum period of uninterrupted sleep by approximately 2 hours compared to placebo 3
• The effectiveness rate ranges from 10-65% with potential for relapse 4

Dosing Recommendations

• Oral tablets: 0.2-0.4 mg taken at least 1 hour before sleep 5
• Oral melt tablets (lyophilisate): 120-240 μg taken 30-60 minutes before bedtime 5
• Newer formulations (Noqdirna) contain lower doses of desmopressin specifically for adults with nocturia due to idiopathic nocturnal polyuria 2
• Dosing is not influenced by body weight or age 5

Important Safety Considerations

• Fluid restriction is essential with desmopressin - evening intake should be limited to 200 ml (6 ounces) or less with no drinking until morning 5, 6
• Polydipsia is a contraindication to desmopressin treatment 5
• Desmopressin combined with excessive fluid intake can cause water intoxication with hyponatremia and convulsions 5
• Clinically significant hyponatremia occurs in approximately 5% of patients and requires withdrawal from treatment in up to 3% of cases 3
• Nasal spray formulations are discouraged due to higher risk of hyponatremia 5
• Regular short drug holidays should be scheduled to assess whether medication is still needed 5

Alternative Pharmacological Options

• Anticholinergic medications (oxybutynin, tolterodine, propiverine) may be considered when desmopressin is ineffective or contraindicated, particularly if there is evidence of detrusor overactivity 5
• Imipramine has been used historically with effectiveness of 40-60% but has higher relapse rates and more side effects than desmopressin 4, 7

Non-Pharmacological Approaches

• Enuresis alarm therapy has a success rate of approximately 66% with better long-term outcomes than medications alone 1, 7
• Regular voiding habits should be established - patients should void regularly during the day and always at bedtime and upon awakening 5, 1
• Fluid management - minimize evening fluid and solute intake while encouraging liberal water intake during morning and early afternoon 5, 1
• Treat constipation if present, as it can cause mechanical pressure on the bladder 4, 8
• Address any underlying sleep disorders, particularly sleep apnea 4

Special Considerations for Adults

• Nocturnal enuresis in older adults is often multifactorial 8
• Hypnotic medication usage should be evaluated as it may contribute to enuresis by causing difficult awakening on bladder distension 8
• Evaluate for and treat any underlying bladder outlet obstruction, especially in older men 8
• For patients with multiple sclerosis and nocturia, desmopressin has been shown to reduce nocturnal voiding episodes by 31-54% 3

Treatment Algorithm

1. Rule out underlying medical conditions (urinary tract infections, diabetes, neurological disorders)
2. Implement non-pharmacological approaches (fluid management, regular voiding habits)
3. Start desmopressin therapy if nocturnal polyuria is confirmed
4. Consider alarm therapy as an alternative or adjunct to medication
5. For treatment failures, consider combination therapy or alternative medications 4, 8