How Do We Make Desmopressin Dose Adjustments in Dogs or Cats with Diabetes Insipidus?

Once a diagnosis of diabetes insipidus has been confirmed, the next step to start replacement treatment with desmopressin.

Initial treatment with desmopressin

Recommended initial doses of desmopressin vary depending on the route it is being administered. In most cats and smaller dogs, 1 to 2 drops of the intranasal preparation administered once or twice daily are sufficient to control polyuria and polydipsia (see Table below).  Larger dogs may require up to 4 to 5 drops twice daily. Use of a tuberculin or insulin syringe allows for more accurate dosing. Application of desmopressin into the conjunctival sac may cause local irritation, as the solution is acidic. Some animals may object to the daily eye drops, making this route of administration ineffective.

With the subcutaneous route of administration, the initial recommended dose is 1.0 to 5.0 μg once or twice daily, depending on the size of the animals. If the nasal solution (100 µg /ml) were used for this purpose, one would inject only 0.01 to 0.05 ml (or 1 to 5 U with a U-100 insulin syringe). With the oral tablets, a starting dose of 0.05 mg to 0.2 mg (50 to 100 µg) once or twice daily is initiated.

Desmopressin dose adjustments

In dogs and cats with central diabetes insipidus, daily administration of desmopressin may completely eliminate polyuria and polydipsia. However, because of individual differences in absorption and metabolism, the dose required to achieve complete, around-the-clock control varies from patient to patient. The maximal effect of desmopressin occurs from 2 to 8 hours after administration, and the duration of action varies form 8 to 24 hours. Larger doses of the drug appear to both increase its antidiuretic effects and prolong its duration of action; however, expense can become a limiting factor for some owners.

No matter what route of administration is used, the daily dose should be gradually adjusted as needed to control signs of polydipsia and polyuria. The morning and evening doses can be adjusted separately if needed.

Adverse effects of desmopressin 

Desmopressin is relatively safe for use in animals with central diabetes insipidus. Adverse effects of desmopressin are uncommon, but overdosage can lead to fluid retention, hyponatremia, and decreased plasma osmolality. Although extremely rare, fluid intoxication associated with desmopressin overdosage can lead to CNS disturbances including depression, increased salivation, vomiting, ataxia, muscle tremors, coma and convulsions. In such instances, furosemide can be given to induce diuresis.

To avoid the potential problem of overdosage, it is recommended that animals not be allowed free access to water immediately after each dose of desmopressin, especially if severe polydipsia and polyuria have redeveloped. Without such short-term (1 to 2 hours) water restriction, the cat many consume excessive amounts of water that cannot be subsequently excreted, as the desmopressin is absorbed and has its peak antidiuretic effects on the renal tubules.

Cost of desmopressin

The principle drawback with the use of any of the desmopressin preparations in the treatment of central diabetes insipidus is the drug’s considerable expense.  The oral route of administration is the most expensive, while the subcutaneous route of administration (using the sterilized nasal solutions) is generally the most cost-effective.

Click on Table to enlarge.

Diagnosis of Diabetes Insipidus: Is the Water Deprivation Test Necessary?

Several different diagnostic approaches can be used to confirm and distinguish central diabetes insipidus, nephrogenic diabetes insipidus and primary (psychogenic) polydipsia. The water deprivation test is generally considered by most authorities to be the best diagnostic test to differentiate between these disorders. However, the water deprivation test has many disadvantages, which include the following:

• The test is very labor intensive
  
• The test can be difficult to perform correctly
  
• The test is quite unpleasant for the dog or cat
  
• The test relies heavily on repeated emptying of the bladder
  
• The test can lead to untoward complications
  
• The test can lead to misdiagnosis in some animals

A simpler and more practical method of diagnosis that I recommended as an alternative to water deprivation testing is evaluation of the clinical response to a closely monitored therapeutic trial with the vasopressin analogue, desmopressin (DDAVP).

Use of the therapeutic trial with desmopressin as a diagnostic test 

This approach is less complicated and time consuming than the water deprivation test, and is certainly easier on the cat. The cost of the two approaches varies according to circumstances but is often comparable. Again, before a desmopressin trial is initiated, it is extremely important to rule out all other common causes of polyuria and polydipsia, limiting the differential diagnosis to central diabetes insipidus, primary nephrogenic diabetes insipidus, and primary (psychogenic) polydipsia. For further information, see my previous blog posts.

To perform the test, the owner should first measure the animal's 24-hour water intake for 2 to 3 days before desmopressin is initiated, allowing free-choice water intake. The dog or cat is then treated with therapeutic dosages of desmopressin (see our next post, What Drugs Do We Use to Treat Diabetes Insipidus).

For the purposes of this test, the desmopressin ideally is administered subcutaneously at the dosage of 1.0 to 4.0 μg twice daily for a period of 5 to 7 days. If subcutaneous injections cannot be given, administration of desmopressin by the conjunctival (1-5 drops twice daily) or oral routes (0.05-2.0 mg twice daily) can be used instead. During this treatment period, the owner should continue to measure the animal’s daily water intake and monitor the degree of urine output.

A dramatic reduction in water intake (>50% of pre-treatment measurements) and polyuria strongly suggests a diagnosis of central diabetes insipidus, whereas a lack of any reduction in polydipsia and polyuria is most consistent with primary nephrogenic diabetes insipidus. With more prolonged treatment, water consumption and urine output should completely normalize in dogs and cats with central diabetes insipidus.

In any older dog or cat that develops diabetes insipidus, one should consider pituitary imaging with computerized tomography or magnetic resonance imaging to exclude a pituitary mass. This is especially true if the affected animal has associated neurological signs.




Computerized tomography (CT) image of the brain of a cat with diabetes insipidus. Note the very large pituitary tumor invading the hypothalamus.