Which patient is most likely to experience tachyphylaxis (rapidly decreasing response to a drug) with desmopressin (DDAVP) use: a patient with central Diabetes Insipidus (DI), nephrogenic Diabetes Insipidus (DI), von Willebrand's disease, or primary nocturnal enuresis?

Tachyphylaxis with Desmopressin Use

Tachyphylaxis is a primary concern with desmopressin use in the 17-year-old girl with von Willebrand's disease (option c), as repeated dosing for hemostatic purposes leads to progressively diminished factor VIII response.

Understanding Tachyphylaxis by Clinical Context

Von Willebrand's Disease - High Risk for Tachyphylaxis

• Desmopressin increases factor VIII activity in von Willebrand's disease Type I patients, but the response diminishes with repeated administration 1
• The mechanism involves V2 receptor stimulation that temporarily releases stored factor VIII from endothelial cells, but these stores become depleted with frequent use 1
• With repeated dosing for bleeding episodes or surgical procedures, patients develop progressively weaker factor VIII responses, making desmopressin less reliable for hemostatic control 1
• This tachyphylaxis typically develops within 24-48 hours of repeated doses and represents a significant clinical limitation when managing acute bleeding

Central Diabetes Insipidus - No Tachyphylaxis

• In central DI, desmopressin acts as hormone replacement therapy for deficient ADH, and long-term administration has not been associated with depression of endogenous ADH secretion or development of tolerance 2
• The 50-year-old man with post-meningitis central DI (option a) can use desmopressin chronically without concern for tachyphylaxis 2
• The antidiuretic effect remains stable over time because the drug is simply replacing a missing hormone rather than stimulating release of limited endogenous stores 1

Nephrogenic Diabetes Insipidus - Ineffective, Not Tachyphylaxis

• Desmopressin is ineffective in nephrogenic DI because the kidneys cannot respond to ADH or its analogs - this is primary resistance, not tachyphylaxis 1
• The 25-year-old woman on lithium with nephrogenic DI (option b) would not be prescribed desmopressin as it provides no therapeutic benefit
• The issue is lack of initial response rather than diminishing response over time

Primary Nocturnal Enuresis - High Relapse, Not True Tachyphylaxis

• Studies report relapse rates as high as 80% with desmopressin for enuresis, but this represents treatment failure after discontinuation rather than tachyphylaxis during active treatment 2
• The 7-year-old child with enuresis (option d) maintains therapeutic response during active treatment, with success rates of 10-65% that remain stable 2
• Regular short drug holidays are recommended to assess ongoing need, not because of tolerance development 3, 4
• The mechanism of action (reducing nocturnal urine production via V2 receptor stimulation) does not involve depletion of limited stores 2

Clinical Implications

• For von Willebrand's disease patients, desmopressin should be reserved for specific hemostatic challenges rather than used repeatedly 1
• Test doses should be performed before planned procedures to confirm adequate factor VIII response
• Alternative hemostatic agents (factor concentrates) should be available when tachyphylaxis is suspected
• The antidiuretic effects of desmopressin remain intact even when hemostatic effects diminish, as these involve different mechanisms 1