What Is the Drug of Choice?

Diabetes insipidus (DI) is a rare endocrine disorder. It’s associated with the body’s problems in the production or action of the antidiuretic hormone (ADH, also known as vasopressin).

ADH is a small hormone made in the brain. It prevents the kidney from releasing too much urine and maintains the body’s water balance.

The main symptoms of DI are extreme thirst and excessive dilute (colorless) urine. These can quickly lead to dehydration. Though these symptoms are also seen with diabetes mellitus (DM), remember that the two conditions are distinct. DM is much more common, and unlike DI, it’s characterized by high blood sugar and problems with a different hormone (insulin).

The following article covers the first-line medications for treating different types of DI, side effects to be aware of, and other ways to manage this condition.

Diabetes Insipidus Medication

Treatment depends on which of the four main types of DI you have. These include the following:

• Central (a lack of ADH)
• Nephrogenic (impacts the kidneys)
• Gestational (occurs during pregnancy)
• Dipsogenic (extreme thirst)

Read on for an overview of the medications commonly prescribed for DI management.

Medication for Central Diabetes Insipidus and Gestational Diabetes Insipidus

Central DI is the most common type of diabetes insipidus. It occurs when the body doesn’t make enough ADH, usually as a result of something like an infection, tumor, or traumatic brain injury (TBI).

Gestational DI can occur during pregnancy. It’s a temporary condition in which an enzyme in the placenta breaks down ADH faster than the body can make it. Gestational DI typically begins in the third trimester and goes away on its own about a month after delivery.

The drug of choice for both central and gestational DI is desmopressin (DDAVP). DDAVP is a synthetic (as in made in a lab) version of the hormone ADH. It mimics the role of ADH in the body, meaning it signals the kidneys to reabsorb water so that the body produces less urine. DDAVP reduces the amount of urine produced more than ADH does, and its effects last longer.

Desmopressin Dosage

DDAVP is available in several dosage forms, such as:

• Nasal spray (brand name Noctiva). This is the recommended dosage form during pregnancy. Typical doses are one to three sprays in a nostril daily for children and one to four sprays daily for adults. The full amount can be taken once a day or divided into two or three doses. Nasal DDAVP kicks in faster than other forms and acts in the body for longer.
• Tablets. The typical daily dose is 0.1 to 1.2 milligrams (mg) divided into two or three doses. These are easy to take by mouth and are less likely to cause electrolyte problems than the nasal spray.
• Sublingual tablets (brand name Nocdurna).
• Injections. DDAVP can be injected under the skin (subcutaneously or SC) or into a vein (intravenously or IV). The usual dose is 2 to 4 micrograms (mcg) daily, which can be taken once a day or divided into two doses.

If you use DDAVP nasal spray or tablets, you’ll start to produce less urine within an hour or two. Effects may last anywhere from six to 18 hours.

Some people with central DI also take thiazide diuretics. Read on for more details about this drug class below.

Medication for Nephrogenic Diabetes Insipidus

Nephrogenic DI occurs when the kidney doesn’t respond to ADH and is unable to concentrate urine.

Common causes of this type of DI in adults include:

Thiazide diuretics are the drugs of choice for nephrogenic DI. It’s strange to think of diuretics (water pills) reducing urination because they can also be used to increase urination. These medicines are thought to work by reducing levels of sodium in the kidneys so that water can be reabsorbed. Thiazide diuretics can reduce the amount of urine produced in nephrogenic DI by up to 70%.

Keep in mind that thiazide diuretics are also an option for central DI.

Thiazide Dosage

Thiazide medicines and dosages used for nephrogenic DI are:

• Microzide (hydrochlorothiazide, or HCTZ) 1 to 2 milligrams per kilogram of body weight daily (mg/kg/day)
• Diuril (chlorothiazide) 5 to 10 mg/kg/day

Thiazide Side Effects

Side effects of thiazide diuretics include low potassium levels and low blood volume in the body (hypovolemia).

Medication for Dipsogenic Diabetes Insipidus

Dipsogenic DI is marked by extreme thirst and over-hydrating. ADH is, in effect, washed away by the extra fluids consumed in this type of DI. Brain abnormalities or injuries most often cause it.

Dipsogenic DI is primarily treated with behavioral therapy and lifestyle changes, not medication.

Interventions that can help manage dipsogenic DI include:

• Reducing fluid intake
• Biofeedback therapy to promote relaxation
• Eating a healthy diet
• Monitoring weight to see if you’re retaining water
• Avoiding medicines that can cause dry mouth
• Sugar-free candy or ice chips that can moisten the mouth

Mental health medications, including antipsychotics and antidepressants, are sometimes taken to help people drink less water and prevent low sodium levels in the body. Some of the medications taken for this include:

• Lithium
• Risperdal (risperidone)
• Zyprexa (olanzapine)
• Wellbutrin (bupropion)
• Inderal (propranolol)

Other Medications and Therapies

Alternative treatments and adjunct therapies that may help manage DI include:

• Fluid management strategies. If you have central or nephrogenic DI, always keep water handy. This will help prevent severe dehydration. On the other hand, if you have dipsogenic DI, you’ll want to be careful to restrict (limit) fluids.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) like Indocin (indomethacin). These medicines can help manage nephrogenic DI. Of note, at high doses, NSAIDs can cause gastrointestinal bleeding and may be toxic to the kidneys.
• Tegretol (carbamazepine), which increases the level of ADH in the body. It can be used for either central or nephrogenic DI.
• Amiloride, another diuretic that can be taken along with thiazides for nephrogenic DI caused by lithium.

Diabetes Insipidus Medication Side Effects

There are some significant side effects to be aware of if you are prescribed a medication for DI. These potential side effects include:

• Electrolyte imbalances. Low sodium levels (hyponatremia) occur in up to one in four people who take DDAVP. In severe cases, low sodium levels can cause seizures, coma, or death. To help prevent this, discuss with your healthcare provider how to limit your fluid intake while DDAVP slows the amount of urine your body produces. You may also measure your electrolyte levels five weeks after starting DDAVP to ensure they’re normal. Thiazide diuretics are associated with low potassium levels (hypokalemia).
• Fluid retention. DDAVP injections may cause fluid retention, which can make some underlying conditions worse (think heart failure or uncontrolled high blood pressure).
• Allergic reactions. DDAVP injections and nasal spray may cause severe reactions, including anaphylaxis, which is life-threatening.
• Nasal scarring and swelling can occur with the DDAVP nasal spray.

Make sure you manage any side effects under healthcare supervision. This will help ensure optimal safety and maximize your therapy.

Supportive Care When Taking Diabetes Insipidus Medication

Supportive care may look different depending on which type of DI you have.

For example, techniques to help manage central DI include:

• Regulating fluid intake, which means drinking the same amount of water every day. This helps prevent electrolyte imbalances. Make sure to consult a healthcare provider or have a plan in place if you vomit, make significant dietary changes, or have to fast for a medical procedure. These can all affect the amount of water you need.
• Monitoring urine output. Babies with DI often need to have their weight checked daily and all wet diapers measured.

Supportive measures for nephrogenic DI include:

• Stopping medications that can cause DI. For optimal safety, make sure to do this only under the supervision of a healthcare provider.
• Eating a renal diet (kidney-friendly), which is low in sodium, protein, and phosphorous.

Diabetes Insipidus vs. Diabetes Mellitus

Though their names are similar, DI and DM are unrelated conditions.

People with DI have normal blood sugar levels, but the kidneys don’t concentrate urine like they should. For the most part, DI can’t be prevented, although some medications make it more likely.

On the other hand, people with DM have high blood sugar (glucose) levels, and some glucose enters the urine. The following can reduce the risk of type 2 DM:

• Exercise
• Achieving a healthy weight
• Eating a balanced diet

If you tell someone you have diabetes, they’ll probably assume you have DM unless you specify DI.

Resources and Support

If you are diagnosed with DI, know that you’re not alone.

Check out resources about DI from these reputable sources:

• The Endocrine Society
• National Institute of Diabetes and Digestive and Kidney Diseases
• The Pituitary Foundation
• Genetic and Rare Diseases Information Center
• NDI (Nephrogenic Diabetes Insipidus) Foundation
• National Organization for Rare Disorders

You’ll find educational materials and online support communities to help empower you on your journey with DI. These resources can also help you stay up to date with the latest research and stay informed about advancements in DI management.

Summary

DI is a condition that results from problems with the hormone ADH. Its main symptoms are extreme thirst and excessive amounts of colorless urine.

Treatment strategies depend on the cause of DI.

The drug of choice for central and gestational DI is an artificial form of ADH called desmopressin (DDAVP). Nephrogenic DI is typically treated with thiazide diuretics like HCTZ.

Potential side effects of DI medications include electrolyte imbalances, fluid retention, and allergic reactions.

Although DI is a rare condition, remember that there are resources and support groups to help you every step of the way.