Demystifying Nocturia: Identifying the Cause and Tailoring the Treatment

Paula Laureanno, RN; Pamela Ellsworth, MD, FACS, FAAP

Disclosures

Urol Nurs. 2010;30(5):276-287. 

In This Article

Pharmacologic Therapy in the Management of Nocturia

There are no FDA-approved agents for the treatment of nocturia. However, depending on the etiology of the nocturia, desmopressin and antimuscarinic agents have been used to treat the nocturia. An oral desmopressin "melt" (Minirin, Ferring, DDAVP), an intranasal formulation of desmopressin (SER-120®) (Serenity Pharmaceuticals and licensed by Allergan), is currently being evaluated for nocturia in clinical trials.

Desmopressin (DDAVP)

Desmopressin is a synthetic analog of the antidiuretic hormone arginine vasopressin. Vasopressin is secreted from the pituitary gland in response to changes in plasma osmotic pressure and increases water reabsorption from the kidney. As an analog of arginine vasopressin, desmopressin increases urine osmolality and decreases total urinary volume (Lose, Lalos, Freeman, van Kerrebroeck, & the Nocturia Study Group, 2003). The molecular structural differences between desmopressin and arginine vasopressin give desmopressin a longer duration of action, an increase in antidiuretic activity, and a decrease in vasopressor activity (Cvetkovic & Plosker, 2005). In healthy men aged 55 to 70 years, oral desmopressin has a half-life of about three hours, with only minor differences between day time and night time values. The median time required to reach the maximum serum concentration is one-and-a-half hours regardless of administration time. The bio availability of desmopressin is low (8%) (Rembratt, Graugaard-Jensen, Senderovitz, Norgaard, & Djurhuus, 2004). The gastrointestinal absorption of desmopressin is decreased and delayed if it is administered within one-and-a-half hours after a meal. However, there is no observed effect of food on the pharmacodynamics of oral desmopressin. Urine volume is decreased, and urine osmolality is increased to similar extents, regardless of the timing of ingestion of food and intake of desmopressin (Rittig, Jensen, Jensen, & Pederson, 1998).

Desmopressin has been used since the 1960s for the treatment of diabetes insipidus and from the early 1980s for the treatment of nocturnal enuresis in children (Asplund, 2007). The first reports of the use of desmopressin for nocturia were published in 1993 (Asplund & Aberg, 1993a, b). The recommended dose of desmopressin for nocturia is 0.1 mg to 0.4 mg orally at bedtime (Asplund, Sundberg, & Bengtsson, 1998). It is recommended to start at the lowest dose and assess the patient's response. Responders to treatment will in most cases note a reduction in nocturnal urine output and nocturnal voids after the first dose or at least after a few days (Asplund, 1992, 1995; Asplund et al., 1998). A good response from treatment is a nocturnal urine output of 350 to 450 ml, including the volume of the void in the morning and one, possibly two, nocturnal micturition episodes. If this goal is not achieved, then the dose of desmopressin can be increased within one week. Serum sodium concentration should be assessed before and three to four days after starting desmopressin, as well as three to four days after each increase in dose.

Efficacy of Desmopressin

The efficacy of desmopressin in treating nocturia has been evaluated in different populations, including men, women, and older adults, in both short-term and long-term studies (Cannon, Carter, & McConnell, 1999; Lose et al., 2003; Mattiasson, Abrams, van Kerrebroeck, Walter, & Weiss, 2002; Rembratt, Norgaard, & Andersson, 2003). The greater the severity of a disorder of the vasopressin system, the higher the sensitivity to desmopressin, and substantial reductions in nocturia and nocturnal polyuria have been noted with the lowest dose of desmopressin (0.1 mg) in individuals with pronounced symptoms (Asplund et al., 1998; Kuo, 2002). In a study of 30 older adults (both men and women) (mean age 75.4 ± 6.6 years) with three or more micturition episodes per night and nocturnal polyuria treated with oral desmopressin 0.1 mg at bedtime for four weeks, nocturnal urine output decreased from a mean of 955 ± 255 ml to 522 ± 210 ml (p < 0.0001). The mean number of nocturnal voiding episodes was also decreased from 5.20 ± 1.16 to 2.24 ± 1.12 per night (p < 0.0001) (Kuo, 2002).

Desmopressin use in nocturia has been shown to improve sleep. In a three-week study by Mattiasson and colleagues (2002), the mean duration of the first sleep period increased by 59% (from 2.7 to 4.5 hours) in the desmopressin group, compared with an increase of 21% (from 2.5 to 2.9 hours) in the placebo group (p < 0.001). Another study evaluated the effects of 12 months of treatment in adult men and women with the optimal dose of desmopressin (0.1 mg, 0.2 mg or 0.4 mg) or placebo (Lose et al., 2004). The mean duration of the first sleep period gradually increased in both men (from 157 minutes to 288 minutes) and women (from 142 minutes to 310 minutes) from baseline to 12 months. The feeling of being well rested in the morning and better day time performance improved in parallel with the sleep improvement. At follow up one month after treatment had been discontinued, the mean duration of the first sleep period had decreased, confirming that the increase was a treatment-related effect (Lose et al., 2004).

Safety and Tolerability of Desmopressin

When treating nocturics with desmopressin, it is important that excess fluid intake be avoided after the medication has been taken. Desmopressin should be discontinued if edema in the legs or other signs of fluid retention occurs. If the antidiuretic effect of desmopressin persists into the day time, the dose may need to be reduced or the desmopressin discontinued (Asplund, 2007).

Adverse events associated with desmopressin treatment include headache, nausea, dizziness, and hyponatremia. The risk of hyponatremia with desmopressin use appears to increase with age and decreasing baseline serum sodium concentration (Rembratt, Riis, & Norgaard, 2006). A systematic review of older adults treated with oral or nasal desmopressin showed an incidence of 7.6% for hyponatremia (Weatherall, 2004). Desmo pressin should be avoided in patients with primary polydipsia and related polyuria, cirrhosis of the liver, renal failure, and congestive heart failure (Abrams, Mattiasson, Lose, & Robertson, 2002).

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