How to manage lithium-induced enuresis with desmopressin (DDAVP)?

Management of Lithium-Induced Enuresis with Desmopressin

Desmopressin is an effective treatment option for lithium-induced enuresis in adults, with response rates of 10-65%, though it requires strict fluid restriction to prevent life-threatening hyponatremia. 1, 2

Understanding Lithium-Induced Enuresis

Lithium causes acquired nephrogenic diabetes insipidus (NDI) by interfering with the kidney's ability to concentrate urine, leading to polyuria and secondary nocturnal enuresis. 3 This is distinct from primary enuresis in children and requires a different therapeutic approach focused on managing the underlying polyuria rather than bladder conditioning.

Desmopressin as Primary Pharmacologic Treatment

Mechanism and Rationale

• Desmopressin is a synthetic analogue of antidiuretic hormone (vasopressin) that decreases nighttime urine production by acting on renal collecting ducts. 1, 4
• For lithium-induced enuresis specifically, desmopressin addresses the nocturnal polyuria component that drives the bedwetting episodes. 1, 5
• Response rates range from 10-65%, with significant individual variation in effectiveness. 1, 2

Dosing Recommendations

• Oral tablets: Start with 0.2 mg taken at least 1 hour before sleep, may increase to 0.4 mg if needed. 1, 5
• Oral melt tablets (lyophilisate): 120-240 μg taken 30-60 minutes before bedtime. 1
• Dosing is not influenced by body weight or age in adults. 1
• Avoid nasal spray formulations due to significantly higher risk of hyponatremia. 1, 5, 6

Critical Safety Considerations

Fluid Restriction (Non-Negotiable)

• Evening fluid intake MUST be limited to 200 ml (6 ounces) or less, with no drinking from the time of desmopressin administration until the following morning. 1, 5, 2
• This restriction is essential to prevent water intoxication, which can cause severe hyponatremia, altered mental status, seizures, and death. 1, 5, 6
• In 54 documented cases of severe hyponatremia with altered mental status or seizures from desmopressin, excess fluid intake was a contributing factor in at least 22 cases. 6

Contraindications and High-Risk Situations

• Polydipsia (excessive thirst/drinking) is an absolute contraindication to desmopressin treatment. 1, 5
• Most severe complications develop within 14 days of starting desmopressin. 6
• Intercurrent illnesses increase risk of hyponatremia—consider temporarily holding desmopressin during acute illness. 6
• Monitor serum sodium levels, especially in the first 2 weeks of therapy. 6

Drug Holidays

• Schedule regular short drug holidays (periodic breaks from medication) to assess whether desmopressin is still needed and to reduce cumulative risk. 1, 5

Limitations and Relapse Considerations

• Relapse rates after stopping desmopressin are high (up to 80%), meaning the medication often provides symptomatic control rather than cure. 4, 2
• Desmopressin provides benefit during treatment but does not address the underlying lithium-induced renal dysfunction. 2, 7
• Some patients may develop decreased responsiveness or shortened duration of effect over time (usually after >6 months), possibly due to local peptide inactivation. 8

Alternative and Adjunctive Approaches

When Desmopressin is Ineffective or Contraindicated

• Anticholinergic medications (oxybutynin, tolterodine, propiverine) may be considered if there is concurrent detrusor overactivity or bladder dysfunction. 1, 4
• Imipramine has historical use with 40-60% effectiveness but carries higher side effect burden and relapse rates compared to desmopressin. 1, 4
• NSAIDs should be avoided in patients taking lithium as they can increase lithium levels and worsen renal function. 3

Non-Pharmacologic Strategies

• Establish regular voiding habits: void regularly during the day and always at bedtime and upon awakening. 1, 5
• Minimize evening fluid and solute intake while encouraging liberal water intake during morning and early afternoon. 1, 5
• Treat constipation if present, as fecal impaction can cause mechanical pressure on the bladder. 5, 4
• Address any underlying sleep disorders, particularly sleep apnea. 1, 4

Clinical Algorithm for Management

1. Confirm lithium-induced polyuria/enuresis by documenting increased nocturnal urine production and ruling out other causes (urinary tract infection, diabetes mellitus, primary polydipsia). 3, 1

2. Assess patient's ability to comply with strict fluid restriction—if patient has polydipsia or cognitive impairment preventing adherence, desmopressin is contraindicated. 1, 5

3. Initiate desmopressin 0.2 mg orally at bedtime with explicit instructions about 200 ml maximum evening fluid intake. 1, 5

4. Monitor closely in first 2 weeks for signs of hyponatremia (headache, nausea, confusion, seizures) and check serum sodium. 6

5. Titrate to 0.4 mg if inadequate response after 2 weeks and patient tolerates initial dose well. 1, 9

6. Schedule drug holidays every 3-6 months to reassess need and reduce cumulative risk. 1, 5

7. If desmopressin fails or is not tolerated, consider anticholinergics if bladder dysfunction is present, or discuss lithium discontinuation/alternative mood stabilizers with psychiatry. 1, 4

Common Pitfalls to Avoid

• Using intranasal formulations instead of oral tablets (47 of 54 severe hyponatremia cases involved intranasal administration). 6
• Inadequate patient education about fluid restriction leading to water intoxication. 1, 5, 6
• Continuing desmopressin during intercurrent illness without reassessment. 6
• Expecting cure rather than symptomatic management—set realistic expectations about relapse after discontinuation. 4, 2
• Failing to coordinate with psychiatry regarding lithium continuation versus alternative mood stabilizers if enuresis significantly impacts quality of life. 3