Desmopressin is widely used to treat nocturia with nocturnal polyuria and helps improve patient quality of life (QOL). While it has been reported to improve the frequency of nocturia and other symptoms, it also has side effects, such as hyponatremia. However, most of the previously reported observational studies have been ≤3 months, and did not address the long-term effects of desmopressin use in the elderly. The effects on body composition due to the characteristics of desmopressin are also of concern; however, these effects have not been studied. In this study, we investigated the efficacy and safety of long-term administration of desmopressin for one year, as well as its effect on body composition.

This retrospective study, conducted at our hospital between August 2020 and December 2022, involved 133 elderly men with nocturnal polyuria and persistent nocturia who were administered an initial dose of 50 µg desmopressin. The efficacy endpoints included nocturnal urinary frequency and volume, hours of undisturbed sleep (HUS), nocturnal polyuria index (NPi), initial nocturnal urinary volume, and daily urinary frequency recorded in a bladder diary before treatment and at 1, 4, 12, 24, and 52 weeks after administration of desmopressin. Additionally, the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Athens Insomnia Scale (AIS), and Geriatric-8 (G8; a measure of frailty), before treatment and at 1, 4, 12, 24, and 52 weeks after treatment, and patient global impression of improvement (PGI-I) after treatment were retrospectively investigated. Additionally, the body water content, body fat mass, and muscle mass were examined using a body composition analyzer (InBody; InBody Japan Inc, Tokyo, Japan) to assess the effects of desmopressin on body composition. Blood samples were taken to assess brain natriuretic peptide (BNP) levels, and chest radiographs were taken to compare the cardiothoracic ratio (CTR) before and 52 weeks after desmopressin administration.

The mean age was 77.7 ± 6.39 years, which was older than that in existing reports. The mean frequency of nocturia at 1, 4, 12, 24, and 52 weeks after treatment initiation was significantly reduced compared with that before treatment (before treatment vs 1w, 4w, 12w, 24w, and 52w; all p<0.001). A more significant decrease occurred at 12 w than at 1 w after the start of treatment (1w vs 12w; p<0.001). There was no statistically significant difference between 12 and 52 weeks (12w vs 52w; p=0.734). In addition, there was no statistically significant difference in daytime urinary frequency before and after desmopressin administration (before treatment vs 1w, 4w, 12w, 24w, 52w; all p>0.05). Night-time urine volume, HUS, NPi, and volume of first night-time urination also significantly improved (before treatment vs 1w, 4w, 12w, 24w, and 52w; all p<0.05). IPSS, IPSS-QOL, OABSS, AIS, and G8 significantly improved compared with before treatment (before treatment vs 1w, 4w, 12w, 24w, and 52w; all p<0.001). The PGI-I score was 1 in 14 patients (14.4%), 2 in 38 patients (39.2%), 3 in 33 patients (34.0%), 4 in 12 patients (12.4%), and none scored ≥5.
The continuation rates at 1, 4, 12, 24, and 52 weeks after administration were 96.9%, 93.2%, 88.7%, 81.9%, and 76.7%, respectively. The most common reason for discontinuation was hyponatremia, which occurred in 10 patients (7.5%). Furthermore, six patients (4.5%) had hyponatremia below 130mEq/l, all of whom developed hyponatremia within the first 4 weeks of treatment. All patients were asymptomatic and all improved after 1 week of discontinuation. Complications, except for hyponatremia, were infrequent: four patients discontinued treatment due to epigastric discomfort, one due to urticaria, one due to discomfort during urination, and one due to heart failure (pleural effusion). In addition, eight patients (6.0%) discontinued treatment at their request and five patients (3.8%) due to interrupted visits to the hospital.
There were no statistically significant differences in weight and body mass index (p=0.082 and 0.104, respectively) or body water content before and after desmopressin administration (p=0.182), including when examined separately for intracellular and extracellular water content (p=0.63 and 0.101, respectively). There were no significant differences in body fat mass, body fat percentage, or muscle mass before or after desmopressin administration (p=0.109, 0.157, and 0.408, respectively). BNP levels were significantly higher 52 weeks after treatment (p=0.006); however, there was no significant change in the cardiothoracic ratio before and after treatment (p=0.425).

This study, which included more than 130 patients and lasted 52 weeks, also showed significant improvements in various endpoints within the first week of treatment compared with pre-treatment, and these improvements persisted after 52 weeks, confirming the efficacy of long-term administration of desmopressin. Evaluation using the PGI-I showed that 87.6% of desmopressin-treated patients had improved symptoms after 52 weeks compared with those before treatment (score ≤ 3). This suggests that long-term administration of desmopressin contributes to improved QOL in patients with nocturnal polyuria. Similarly, the G8 score improved after 52 weeks of desmopressin administration, suggesting that long-term desmopressin treatment may improve frailty. Moreover, HUS was approximately 2 hours longer after 52 weeks’ administration and the AIS score, a measure of insomnia, also improved accordingly, suggesting that long-term treatment with desmopressin may improve sleep quality. Considering adverse reactions of concern, although hyponatremia occurs in a certain proportion of patients, it is rarely symptomatic, and all patients in this study were asymptomatic. In all the patients in whom serum Na fell below 130 mEq/l, the onset was within the first month; therefore, cautious monitoring is required for the first month of administration. After the first month of desmopressin administration, however, serum Na levels did not become excessively low in any patient, suggesting that the interval between tests may be extended. Desmopressin is an arginine-vasopressin (AVP) derivative that promotes water resorption in the collecting ducts of the kidneys via V2 receptors; therefore, complications involving water retention in the body are a concern. Compared with baseline, no significant changes in weight, BMI, body water content, body fat mass, and muscle mass were observed after administration. Although the BNP level rose, there was no change in the cardiothoracic ratio, suggesting that desmopressin may present few clinically problematic effects on body composition even when administered long-term.

This is the first study to examine the effects of long-term desmopressin administration on elderly patients with nocturnal polyuria using a 52-week bladder diary and a body composition analyzer. Desmopressin is effective in elderly patients with nocturnal polyuria and is relatively safe for long-term administration. Moreover, desmopressin has little effect on body composition, suggesting that understanding the timing of adverse effects may help avoid unnecessary testing.

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Yamaguchi O, Juul KV, Falahati A, et al: Efficacy and safety of 25 and 50 µg desmopressin orally disintegrating tablets in Japanese patients with nocturia due to nocturnal polyuria: Results from two phase 3 studies of a multicenter randomized double-blind placebo-controlled parallel-group development program. Low Urin Tract Symptoms 12(1): 8-19, 2020.

Continence 12S (2024) 101535
DOI: 10.1016/j.cont.2024.101535