Treatment of Nocturia Related to Low Bladder Capacity
Few clinical trials have specifically evaluated the use of medications for treating nocturia by improving bladder capacity. While the evidence base for use of antimuscarinic agents to treat nocturia has not been established, these drugs have been investigated in studies of over-active bladder (OAB) syndrome, of which nocturia is a common symptom.
Darifenacin (Enablex®). The effects of darifenacin on nocturia are variable. Improvements in weekly nocturia episodes were observed in one 12-week, placebocontrolled trial (Hill, Khullar, Wyndaele, Lheritier, & the Darifenacin Study Group, 2006), while no improvement was seen in another trial of similar duration (Haab, Stewart, & Dwyer, 2004). In a pooled analysis of three phase III studies to evaluate the efficacy, tolerability, and safety of darifenacin, the decrease in number of nocturnal awakenings per week caused by OAB was greater with darifenacin than placebo, although the between-group difference was not statistically significant. The median change from baseline for darifenacin 7.5 mg was -1.7 vs. -0.8 for placebo and -1.9 for darifencacin 15 mg versus -1.1 for placebo (Chapple et al., 2005). In a two-year, non-comparative, open-label extension study with darifenacin 7.5 mg and 15 mg, the median change in nocturnal awakenings at 24 months was -1.5 (14.3% change) (Haab et al., 2006).
Fesoterodine (Toviaz®). In a randomized, placebo-controlled, double-blind multi-center trial performed in the United States comparing fesoterodine 4 mg or 8 mg to placebo, fesoterodine 4 mg showed significant improvement in mean change from baseline compared to placebo for the number of nocturnal micturitions (p < 0.05). The mean percent change from baseline for placebo was -25.5%, for fesoterodine (4 mg) it was -33.3%, and for fesoterodine (8 mg) it was -25% (Nitti et al, 2007). Several other clinical trials with fesoterodine have demonstrated a decrease in nocturnal voids/24 hours. However, when compared to placebo, the difference was not statistically significant (Chapple et al., 2007; Dmochowski et al., 2010; Hesrchorn et al., 2009).
Oxybutynin (Ditropan®). Published data are limited regarding the efficacy of oxybutynin for nocturia. In a placebo-controlled trial investigating the effects of behavioral and drug therapy on nocturia in older incontinent women, oxybutynin decreased nocturia episodes significantly more than placebo, though these effects were less than those observed with behavioral modification (Johnson, Burgio, Redden, Wright, & Goode, 2005).
Solifenacin (Vesicare®). An analysis of whether patients with OAB and nocturia achieved relief of night time voiding symptoms when treated with solifenacin and if having nocturnal polyuria affected the response was performed using pooled data from four phase III clinical trials. The first analysis looked at reductions in nocturia episodes after treatment with solifenacin (5 mg or 10 mg), and a second analysis was performed in patients with and without nocturnal polyuria. Patients were considered to have nocturnal polyuria if their nocturnal urinary volume was greater than the percentage of hours in the day asleep multiplied by the 24-hour urine volume (Weiss & Blaivas, 2000). Statistically significant reductions in nocturia episodes were noted in patients treated with solifenacin. Median reductions were -35.5% for 5 mg solifenacin and -36.4% for 10 mg solifenacin compared to -15% for placebo (p = 0.021 and p < 0.001, respectively). In addition, significantly more patients treated with solifenacin versus placebo achieved a median nocturic frequency of one episode/night or fewer. Solifenacin reduced nocturia episodes only in patients without nocturnal polyuria. In those patients treated with solifenacin without nocturnal polyuria, more than 60% achieved an average of one nocturic episode nightly or fewer by the end of the study (Brubaker & Fitzgerald, 2007).
Tolterodine (Detrol®). The efficacy and tolerability of night time tolterodine dosing on urgency-related micturitions in patients with OAB and nocturia were assessed. In this study, changes in the number of night time and 24-hour micturitions were analyzed using a 5-point urgency rating scale for each micturtition, ranging from no urgency to severe urgency and urgency urinary incontinence. Tolterodine ER was noted to decrease the total number of nocturnal micturitions, compared to placebo, though the difference was not statistically significant. Tolterodine ER did, however, significantly reduce OAB-related and severe OABrelated nocturnal micturitions compared to placebo. No effect was reported on non-OAB micturitions (Rackley et al., 2006).
A six-month, open-label trial in 43 men with BPH-related symptoms who failed alphablocker therapy was conducted. These men were treated with tolterodine ER 4 mg and demonstrated a reduction in nocturnal voids from 4.1 episodes per night to 2.9 episodes per night (Kaplan, Walmsley, & Te, 2005).
Trospium chloride IR and XR (Sanctura®). A multi-center, placebo-controlled trial involving 134 men and 389 women with OAB and urge incontinence was conducted. The sample was randomized to receive either trospium chloride 20 mg twice a day (BID) or placebo for 12 weeks. The trospium chloride-treated pa tients showed a statistically significant decrease in the average number of nocturnal voids after week four (p < 0.001) and week 12 (p < 0.05), but not at week one (Zinner et al., 2004).
An analysis using pooled data from two identically designed phase III trials involving males and females compared trospium chloride extended release to placebo. A significantly greater mean reduction from baseline in nocturnal voids (0.8 vs. -0.6, p = 0.006) was noted. Reductions in nocturnal voids were accompanied by significant improvements in sleep-related quality-of-life domains (Ginsberg, Oefelein, & Ellsworth, 2009).
A subgroup analysis of male patients from two large, phase III, double-blind, randomized, placebo-controlled studies evaluated tropsium chloride extended release versus placebo. A greater decrease from baseline with trospium chloride extended release compared to placebo was noted for nocturnal voids (-0.9 vs. -0.5, p < 0.05) (MacDiarmid, Ellsworth, Ginsberg, Oefelein, & Sussman, 2009).
Nocturia and Benign Prostatic Hyperplasia (BPH)
Variable results have been demonstrated for the effects of alpha blockers and 5-alphareductase inhibitors on nocturia in men with benign prostatic hyperplasia (BPH). In the VA cooperative study program trial, 1978 men with BPH had baseline nocturia of 2.5 episodes per night. They were randomized to receive terazosin (Hytrin®), finasteride (Proscar®), terazosin plus finasteride, or placebo. Nocturia episodes decreased to around two per night for all groups, including placebo. No significant difference was found among any treatment arms, including placebo (Johnson et al., 2003).
In an observational study evaluating an extended release formulation of alfuzosin (Uroxatral®) 10 mg/day, 144 of the males had more than two nightly voids at the start of the study, and 51.4% improved to two nightly voids or fewer after nine days of treatment. At three months on treatment, 60.4% had two nightly voids or fewer (Roehrborn, van Kerrebroeck, & Nordling, 2003). A pooled analysis of three double-blind studies noted alfuzosin improved nocturia in patients with BPH (Saad et al., 2005). In a long-term study, the occurrence of three or more nocturnal voiding episodes was decreased by two-thirds after three months of therapy with alfuzosin, with these results being maintained at two years (Elhilali et al., 2006).
The effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of BPH was analyzed. The analysis included 2583 men with at least one nocturnal void per night who were randomized to receive doxazosin (Cardura®) alone, finasteride alone, combination therapy, or placebo, and were followed for at least 12 months of the four-year study period. Doxazosin alone and combination therapy led to a statistically significant reduction in nocturnal voids. Mean nocturia was reduced at one year by 0.35, 0.40, 0.54, and 0.58 for placebo, finasteride, doxazosin, and combination groups, respectively. Similar results were seen at one year and four years (Johnson et al., 2007). The clinical impact of this change on quality of life was not assessed.
Little data are available regarding the effect of 5-alphareductase inhibitors on nocturia. Two studies have demonstrated no effect of finasteride monotherapy on nocturia (Johnson et al., 2003, 2007). In a prospective, multi-center, open-label study evaluating the effect of dutasteride 0.5 mg/day on the symptoms of BPH, a decrease from baseline at 12 weeks and 24 weeks with respect to Q7 of the International Prostate Symptom Score (IPPS) was noted. Q7 of the IPPS refers to how many times a person most typically gets up to urinate from bedtime until getting up in the morning. Significant reductions of -0.5 and -0.6 nocturnal voids were also noted at 12 weeks (p < 0.001 for each) (Desgrandchamps, Droupy, Irani, Saussine, & Comenducci, 2006).
Urol Nurs. 2010;30(5):276-287. © 2010
Society of Urologic Nurses and Associates
Cite this: Demystifying Nocturia: Identifying the Cause and Tailoring the Treatment - Medscape - Sep 01, 2010.