Nocturia is one of the most common and also the most bothersome lower urinary tract symptom in adults. Incidence and prevalence rates of nocturia increase with advancing age and the condition frequently occurs in geriatric patients.¹ The etiology is often multifactorial and may include nocturnal polyuria, increased evening fluid consumption, peripheral edema, congestive heart failure, electrolyte imbalances and sleep apnea or other sleep disturbances. Sleep apnea has been linked to reductions in antidiuretic hormone (ADH) secretion which can increase nighttime volume of urine output. Men with benign prostatic hyperplasia may also experience bothersome nocturia. Getting up once per night is usually considered normal, but getting up 2 or more times a night has been shown to have negative outcomes on overall and health related quality of life.² Nocturia has been associated with a variety of negative clinical outcomes including increased rates of falls and fractures as well as mortality.^3,4

A multicomponent approach is often used for the treatment of nocturia. Adjustments in fluid consumption, leg elevation prior to going to bed for the night, exercise and other similar measures have been advocated as behavioral options that can help some patients. Use of continuous positive airway pressure can be quite helpful in patients with sleep apnea. This can reduce sleep disruption itself from improvement in ventilation and elimination of apneic intervals. This has also been shown to increase natural production of ADH in affected patients, which in turn can lead to a reduction in the volume of nocturnal urine production.

Administration of exogenous arginine vasopressin (desmopressin) has long been used in the treatment of nocturnal enuresis in pediatric patients. However, similar use in elderly patients has been more problematic in the past due to risk of symptomatic hyponatremia or other potential complications. Ongoing research and development of some newer formulations and methods of administration has led to renewed interest in use of this medication for the treatment of nocturia in adults. However, use of this medication in the geriatric patient population remains controversial.

A crossfire debate on the topic will be featured in the plenary sessions at the upcoming AUA Annual Meeting. I will have the pleasure of moderating this debate on Sunday, September 12 (3:45 p.m. to 4:15 p.m.). I will be joined by 4 friends and colleagues who are all internationally recognized experts in the topic of nocturia. These include Dr. Alan Wein of the University of Pennsylvania, Dr. Roger Dmochowski of Vanderbilt University, Dr. Jeffrey Weiss of the State University of New York (SUNY) Downstate at Brooklyn and Dr. Kari Tikkinen of the University of Helsinki in Finland. We recently had an opportunity to chat about some of the main considerations regarding use of desmopressin for treatment of nocturia and nocturnal polyuria specifically in geriatric patients.

Griebling: Who do you feel are the best candidates for desmopressin therapy to treat nocturia and how do you approach clinical decisions in this population?

Dmochowski: Patients with nocturnal polyuria syndrome who are bothered from the condition and have minimal to no comorbidities. Age is not a criterion.

Wein: For individuals without significant cormobidities who have made an honest try at simple behavioral interventions and have failed, especially those who are getting up more than twice a night. I think it reasonable to try desmopressin with all of the usual precautions and checks.

Tikkinen: First of all, a complete medical assessment should be made before using desmopressin. I use it very selectively in some, mostly in middle-aged patients after diagnosing nocturnal polyuria and after exclusion of other causes such as sleep apnea.

Weiss: In my opinion, the ideal patient for desmopressin has the “Nocturnal Polyuria Syndrome,” in other words, nocturnal urine overproduction with no identifiable cause such as cardiac factors, peripheral edema, diabetes insipidus, glycosuria, obstructive sleep apnea, primary polydipsia. With increasing age, one sees increasing tendency to nocturnal urine overproduction.

Griebling: Are there any patients for whom you would specifically not use this therapy?

Wein: As physicians, we use many medications that are potentially hazardous to patients of both genders, especially those with many comorbidities. Unfortunately, this generally falls into that group considered to be elderly. Many of these comorbid factors are associated with nocturia, and I would not use desmopressin in this group until all efforts have been exhausted to correct these factors. Examples include congestive heart failure, peripheral edema from other causes, poorly controlled or brittle diabetes, poorly controlled hypertension, and sleep disorders such as obstructive sleep apnea.

Dmochowski: Contraindications would include significant fluid volume status dysfunction such as congestive heart failure, significant renal filtration dysfunction, and patients who have cognitive impairment. Age alone should not be a criterion for exclusion.

Tikkinen: I have not used desmopressin in those aged 75 years or more. I think we need more evidence from controlled clinical trials regarding safety in elderly patients.

Griebling: Do patients need an analysis for nocturnal polyuria?

Weiss: Yes. This would include a check for peripheral edema, polysomnography for suspected sleep apnea, and ambulatory blood pressure monitoring for nocturnal nondipping hypertension.

Dmochowski: Yes, I have the patients keep a diary and determine nocturnal polyuria, which I define as greater then 30% of overall output at night. I also do a good screening evaluation for other medical comorbidities, including any edematous disorders and the possibility of sleep apnea.

Griebling: What about sleep apnea? Do patients need formal sleep studies?

Weiss: Yes, if patients have nocturnal polyuria and no other explanation, then sleep studies are indicated.

Dmochowski: Yes, this has become a routine part of my treatment for these patients, given the ability to abrogate much of the impact of polyuria with this intervention. Patient unwillingness to utilize external devices, however, somewhat mitigates against success of therapies for sleep apnea.

Griebling: What formulations of desmopressin do you typically prescribe? Oral melts? Pills? Nasal spray has been used in children in the past for nocturnal enuresis, but this has recently been recalled.

Dmochowski: Currently we only really have an adult formulation of pills or melts. I think any formulation that provides rapid onset and short half-life is reasonable. Microdosing is another advantage of some formulations.

Weiss: Oral melt formulations with sex-specific dosing of 55 mcg in men or 27 mcg in women. If treating patients in their 80s or 90s, they must be robust (not frail) and willing to go for periodic serum sodium checks. I tell them to use desmopressin every other night. This obviates any need for sodium monitoring. The idea of sleeping well every other night beats never sleeping well at all.

Griebling: Hyponatremia is, of course, one of the main concerns, particularly in older adults. Do you think patients need routine monitoring of serum sodium levels?

Tikkinen: Surely baseline hyponatremia must be excluded prior to starting desmopressin therapy, and serum sodium levels must be monitored carefully.

Dmochowski: Hyponatremia is not as predictable as we would like and certainly requires sedulous observation over time.

Griebling: What about safety of long-term use?

Dmochowski: Some patients are doing very well with long-term use, but again this presumes observation and close followup.

Weiss: Studies and my personal experience demonstrate desmopressin is safe especially when there are no short-term complications such as transitory hyponatremia. If a mid-day diuretic is added, then monitoring for hypokalemia should be included.

Griebling: Do you regularly involve other clinicians, including primary care or specialists in geriatrics or cardiology, in the management of your patients?

Weiss: No, not really, although their input can be useful, of course.

Dmochowski: Yes, management with primary care and interested geriatricians or internists is very useful and can decrease the burden for the patient and health care system by sharing visits and observations.

Griebling: Any other closing thoughts?

Weiss: I would emphasize the importance of the nondipping blood pressure concept of nocturnal polyuria induced by pressure-natriuresis. Ambulatory blood pressure monitoring is needed to properly diagnose this condition.

Tikkinen: No, I agree with the points that have already been made. But I certainly look forward to ongoing conversations on this topic.

Dmochowski: I want to highlight the issues of frailty and some of the emerging research on this crucial topic in older adults.

Wein: I’m looking forward to our continued discussions and the upcoming debate.

Griebling: Thank you all for a great discussion on this important and controversial clinical topic. I look forward to our in-person debate at the upcoming meeting and for future research results.