OAB is a symptom syndrome consisting of urgency, with or without urgency incontinence, usually with frequency and nocturia [1
], and is a common and distressing condition known to have an adverse effect on QoL [2
]. First-line therapy for OAB includes conservative treatment in the form of lifestyle intervention, pelvic floor exercises, and bladder training. These offer better results when combined with anticholinergics, which are the first-line medical therapy for OAB. However, anticholinergic medication is associated with typical side effects, including dry mouth, constipation, and blurred vision. Compliance with anticholinergic medication is also a significant problem. In a questionnaire follow-up study of women with OAB, only 5.5% were cured of their OAB symptoms and only 18.2% of women continued drug therapy for longer than 6 months [7
For OAB patients who are refractory to anticholinergics, modalities such as botulinum toxin injection, neuromodulation, and various surgical interventions can be attempted. However, these also have side effects and limitations and are not curative. Therefore, discovery of alternative modalities of medical treatment for OAB, which could delay any invasive treatments, is crucial.
Desmopressin (1-desamino-8-D-arginine vasopressin) is a synthetic nonapeptide analogue of antidiuretic hormone that affects renal water reabsorption, leading to decreased urine production. To date, desmopressin has been used in the treatment of disorders such as diabetes insipidus, primary nocturnal enuresis, and nocturia with a polyuric background.
Well-controlled trials have been performed to evaluate the safety, efficacy, and tolerability of desmopressin in the treatment of patients with nocturia [13
]. Duration of the period from bedtime until the first nocturnal void (first sleep period) is one of the frequently used efficacy end points in clinical trials for evaluation of the efficacy of desmopressin in patients with nocturia; findings from previously reported studies have shown an increase in the first sleep period of 1.5 to 2.2 hours [17
Some recent studies have reported the efficacy of desmopressin in patients with OAB [10
]. The rationale for use of desmopressin in the treatment of OAB patients is that through a decrease in urine production, desmopressin will increase the time taken to reach functional bladder capacity between daytime voids, thereby reducing frequency and urgency and benefiting adults suffering from OAB. This is very similar to the rationale for use of desmopressin in nocturia patients; therefore, we used the time to the first OAB symptom episode (micturition and urgency) as the primary end point, because in previous desmopressin trials, the concept of time to the first nocturnal void was used and this was increased by use of desmopressin, resulting in a greater number of hours of undisturbed sleep [14
Robinson et al administered 40 µg intranasal desmopressin to 64 women with urinary incontinence lasting over 10 days [11
]. Results showed that patients taking desmopressin had a significantly higher mean incidence of periods with no leakage during the first 4 and 8 hours after taking desmopressin. This study was the first to explore the concept of antidiuresis as a strategy for management of daytime OAB symptoms in women and the results were very encouraging; however, it did not look at the effect on other OAB symptoms, such as frequency and urgency.
Recently, in a double-blind placebo-controlled trial that evaluated the efficacy of desmopressin in the treatment of female patients with OAB, desmopressin induced a significant increase in the time to the first urgency episode, with a significant reduction in the mean numbers of urgency episodes, compared to placebo, and subjective improvement was observed in frequency and urgency as well as overall QoL [10
Currently, anticholinergics are the primary treatment for OAB; therefore, unlike previous studies [10
] concerning the efficacy of desmopressin in patients with OAB, which compared the desmopressin group and the placebo group, our study was designed to address the issue of pharmacological antidiuresis in OAB patients who take anticholinergic medication.
Like the previous studies, we analyzed the changes in OAB symptoms during the first 8 hours of the day following medication because it is known that desmopressin is most effective during this period.
In our study, desmopressin did not induce a significant increase in the time to the first frequency episode; however, the time to the first urgency episode increased and the numbers of frequency and urgency episodes showed a significant decrease in the desmopressin with anticholinergics group. In addition, QoL as measured by the UDI-6 and IIQ-7 showed significant improvement in the desmopressin with anticholinergics group. These results are similar to those of the previous study [10
]. In the future, antidiuresis using desmopressin could have potential for use in the treatment of OAB.
The effects of desmopressin in our patients were probably due to the decreased urine volume in the daytime. However, we did not analyze the changes in urine volume because measurement of urinary output was incomplete in most of our patients, and this may be one drawback of the study. In addition, the 2-week period of our study was too short to conclude that combined therapy is more effective than anticholinergics alone on a long-term basis, because the effect of anticholinergics could be gradually increased up to 2 to 3 months. Therefore, larger long-term studies will need to be conducted to prove the concept that reduction in urine volume production helps in OAB patients and to determine the long-term effect of combined therapy.
There have been no reports concerning the predictive factors for the effect of desmopressin with anticholinergics in OAB patients. Therefore, we performed subanalysis of the desmopressin with anticholinergics group to evaluate the outcome predictors of desmopressin in OAB patients. Age (>65 years) and voided volume (>150 ml) showed a significant association with improvement of OAB symptoms after desmopressin medication.
However, these results had some drawbacks, because it is not known how many increases in time to first void is needed to improve QoL, and the number of patients in the desmopressin with anticholinergics group was small. Therefore, the outcome predictors of desmopressin with anticholinergics in OAB patients should be explored further in a larger confirmatory trial.
Hyponatremia is the only serious potential adverse event associated with the use of desmopressin [18
]. In the present study, desmopressin was well tolerated by the majority of patients. No significant hyponatremia was reported in any patient. However, significant hyponatremia occurred in 4% to 6% of patients in the published trials [21
], particularly in patients over the age of 65 years. Therefore, precautions should be taken in older patients, including close monitoring of prodromal symptoms, such as headache and weight increase, and avoidance of excessive fluid intake.