What to monitor when adding desmopressin to a patient's regimen who is already taking lithium (lithium carbonate) for enuresis (nocturnal enuresis)?

Monitoring Requirements for Desmopressin Added to Lithium Therapy

When adding desmopressin to a patient already taking lithium, you must monitor serum sodium levels intensively due to the compounded risk of severe, life-threatening hyponatremia—measure serum sodium at baseline (must be ≥135 mmol/L to proceed), within 7 days, at 1 month, and periodically thereafter, with more frequent monitoring if any risk factors emerge. 1

Critical Baseline Assessment

Before initiating desmopressin in a lithium-treated patient:

• Verify serum sodium is normal (≥135 mmol/L) - this is mandatory and treatment cannot proceed if sodium is below this threshold 1, 2
• Assess for polydipsia - this is an absolute contraindication to desmopressin, as excessive fluid intake dramatically increases hyponatremia risk 3, 4
• Check renal function - lithium commonly causes nephrogenic diabetes insipidus and impaired kidney function, both of which increase hyponatremia risk 2, 5
• Review all concurrent medications - the FDA explicitly contraindicates desmopressin in patients using loop diuretics or systemic/inhaled glucocorticoids due to severe hyponatremia risk 1

Sodium Monitoring Schedule

The FDA-mandated monitoring protocol requires:

• Baseline serum sodium measurement before starting desmopressin 1
• Within 7 days of initiating therapy 1
• At approximately 1 month after starting 1
• Periodically during ongoing treatment 1
• More frequently in high-risk patients, including those on lithium who may have compromised renal function 1, 2

Recent evidence suggests that capillary blood sodium monitoring via finger prick is interchangeable with venous sampling (ICC 0.82), potentially allowing for more frequent and convenient monitoring in high-risk patients 6

Fluid Restriction Counseling

Strict fluid restriction is non-negotiable to prevent water intoxication:

• Limit evening fluid intake to 200 mL (6 ounces) or less after taking desmopressin 3, 7, 4
• No drinking from evening dose until morning 3, 4
• Educate the patient and family explicitly about the risk of water intoxication leading to seizures, coma, or death 1, 8

This is particularly critical because lithium patients may already have altered thirst mechanisms or polyuria from nephrogenic diabetes insipidus 5

Clinical Monitoring Parameters

Beyond sodium levels, monitor for:

• Neurological symptoms - confusion, headache, nausea, seizures, or altered mental status indicate possible hyponatremia and require immediate sodium measurement 1, 8
• Urine output changes - sudden changes may indicate either treatment effect or developing complications 3
• Lithium levels - ensure therapeutic monitoring continues, as fluid balance changes could affect lithium concentrations 5
• Renal function - measure serum creatinine and estimated GFR, as declining kidney function increases hyponatremia risk 2

High-Risk Considerations in Lithium Patients

Patients on chronic lithium face compounded risks:

• Lithium-induced nephrogenic diabetes insipidus is common and may mask or complicate the clinical picture 5
• Rarely, lithium can cause central diabetes insipidus, which would actually be an indication for desmopressin, but this requires careful diagnostic workup 5
• Age-related risk - if the patient is ≥65 years old, monitoring must be even more frequent 1
• Baseline renal impairment from chronic lithium use increases hyponatremia susceptibility 2

Dosing Strategy to Minimize Risk

Use the minimum effective dose approach:

• Start with lower doses (0.2 mg tablets or 120 μg melt formulation) rather than maximum doses 3, 4
• Implement regular drug holidays to assess ongoing need and reduce cumulative exposure 3, 4
• Avoid nasal spray formulations - these carry higher hyponatremia risk and have had the enuresis indication removed in many countries 3, 4

When to Stop or Hold Desmopressin

If serum sodium drops below 135 mmol/L or the patient develops neurological symptoms, desmopressin may need temporary or permanent discontinuation 1. However, if treating symptomatic hyponatremia with hypertonic saline, paradoxically continue desmopressin to prevent overly rapid autocorrection during water diuresis, which could cause osmotic demyelination 9

Common Pitfalls to Avoid

• Inadequate fluid restriction counseling - families must understand the 200 mL limit is absolute, not a suggestion 3, 4, 8
• Assuming nephrogenic diabetes insipidus from lithium without considering central causes - both can occur with lithium 5
• Failing to check baseline sodium - treatment should never start without confirming normal sodium 1
• Insufficient monitoring frequency - the first week and first month are highest risk periods 1, 8, 2
• Not screening for polydipsia - this is an absolute contraindication that must be identified before prescribing 3, 4