Low-dose desmopressin became available in Japan in 2019 for treating nocturia associated with nocturnal polyuria, and our group has previously reported the efficacy and safety of this drug. However, there have been almost no reports on investigations into the efficacy, safety and effect predictors of long-term administration. Nocturia affects sleep. Both quality of sleep and quality of life (QOL) are known to decline with a night time frequency of two or more voids. It is important to secure three hours of hours of undisturbed sleep (HUS) to attain high-quality, slow wave sleep (SWS). This study examined the therapeutic effect predictors in patients who were able to achieve three or more hours of HUS upon administration of desmopressin. These were defined as marked response cases. The efficacy of the long-term administration of desmopressin was also investigated.

Participants were 102 patients who had received Desmopressin for nocturnal polyuria in our hospital. Efficacy and safety after 1 week, 4 weeks, 12 weeks, 24 weeks, and 52 weeks were noted by means of a bladder diary, the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), patient global impression of improvement (PGI-I), Athens Insomnia Scale (AIS), G8, blood tests, and body composition analyzer (In body). It was found that there was no fixed definition of a marked response in these cases of nocturia. However, as it is a disease that affects QOL, when cases with good PGI-I scores (Score of 1 or 2) were investigated, patients with good PGI-I scores (Score of 1 or 2) had significantly longer HUS after the administration of Desmopressin than patients with a score of 3 or higher. Therefore, patients with HUS of three or more hours were defined as marked response cases. Effect predictors were investigated in relation to age; Body Mass Index (BMI); body water content; body fat mass; muscle mass; eGFR, night time urine volume; mean night time urine volume; mean urine volume; nocturnal polyuria index; and night time frequency before the administration of desmopressin.

The mean age of the participants was 78.0 years. Significant improvement was evident in each of the variables investigated, as noted in their bladder diaries after one week, compared to before the administration of the medication. The mean night time frequency improved from 3.85 before administration to 1.62 after 52 weeks (p < 0.0001). HUS lengthened from 134 minutes before administration to 250 minutes after 52 weeks (p < 0.0001). Further significant improvement was seen in both the night time frequency and HUS from 12 weeks onwards, compared with one week after the initiation of administration (1 week vs 12 weeks, 24 weeks, 52 weeks: all p < 0.001). There were also significant improvements in the night time urine volume, nocturnal polyuria index, daily urinary frequency, volume of first night time void, IPSS, IPSS-QOL, OABSS, and G8 (all p < 0.05). Significant progress was manifest on the AIS (p < 0.0001), with a positive correlation between the amount of change in HUS and the amount of change on the AIS (p = 0.005, Pearson’s correlation coefficient: 0.325). Furthermore, the greater the change in HUS after administration, the better the PGI-I score (p < 0.0001, Pearson’s correlation coefficient: -0.489), suggesting that both quality of sleep and QOL improved with the administration of desmopressin. The continuation rate was high, with 93.1% at 4 weeks, 89.1% at 12 weeks, 81.2% at 24 weeks, and 71.7% at 52 weeks. Hyponatremia resulted in 5% of the patients discontinuing administration. A low serum Na level prior to administration was found to be an independent predictor in a multivariate analysis of predictive factors for hyponatremia (p < 0.05), and factors such as weight, BMI, and body water content were not significant factors. 16.7% of patients had a PGI-I score of 1, 35.9% patients had a score of 2, 32.0% patients had a score of 3, 15.3% patients had a score of 4, and there were no patients with a score of 5 or more. Patients with a good PGI-I had longer HUS after administration, and there was a significantly higher number of patients with a night time frequency of one void or less (p < 0.05). Examination of effect predictors, with an HUS of three or more hours defined as markedly effective, revealed that the mean night time urine volume was an independent effect predictor (p < 0.05). Muscle mass, body fat mass, and body water content were found not to be predictors.

In this study, Desmopressin was found to be effective for Japanese patients with nocturnal polyuria. The treatment became more effective from 12 weeks onwards, compared to one week after administration, suggesting that long-term administration of desmopressin is effective. The continuation rate was also high, indicating that it is possible to use Desmopressin safely in the long term. The relationship between HUS, AIS and PGI-I demonstrated that Desmopressin prolonging HUS improved both quality of sleep and patient QOL. The improvement in G8, a measure of frailty, further supports the finding that Desmopressin contributes to improvement in QOL. Results of the examination of effect predictors suggest that desmopressin is effective in patients with a high mean night time urine volume before its administration. Individuals with a high mean night time urine volume tend not to suffer from urine storage dysfunction or sleep disorders. It is, therefore, important to evaluate whether patients have a urine storage dysfunction or sleep disorder using a bladder diary when treating nocturia. In order to ensure efficacy, the findings suggest that the treatment of a urine storage dysfunction, sleep disorder, and low mean night time urine volume should be prioritized before prescribing desmopressin.

To the best of our knowledge, this is the first study to evaluate the predictors of desmopressin efficacy in the context of HUS. Nocturia is a symptom that causes reduced quality of sleep, and inhibits QOL. The findings indicate that desmopressin improves quality of sleep and QOL by extending HUS; and suggest that desmopressin may be particularly effective for patients with a high mean night time urine volume based on their bladder diary.

Kurose H, Ogasawara N, Ueda K, et al: Determining the optimal initial dose for Japanese patients with nocturnal polyuria using an initial dose of desmopressin 50 µg. Low Urin Tract Symptoms: 2023 doi.org/10.1111/luts.12474
Kyoda Y, Kimura M, Shimizu T, et al: Efficacy and safety of desmopressin orally disintegrating tablets 25 and 50?µg in male patients with nocturia: A Japanese real-world multicenter clinical study. Low Urin Tract Symptoms 14: 410-415, 2022.
Bae WJ, Bae JH, Kim SW, et al.: Desmopressin add-on therapy for refractory nocturia in men receiving a-blockers for lower urinary tract symptoms. J Urol 190: 180-186, 2013.

Continence 7S1 (2023) 100789
DOI: 10.1016/j.cont.2023.100789