Mirabegron should be considered as a potential treatment option for patients who demonstrate poor tolerance of or response to anticholinergic medications; however, caution should be used in patients with severe uncontrolled high BP, end-stage kidney disease, or severe liver impairment.
Peters KM, Macdiarmid SA, Wooldridge LS, et al. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: Results from the overactive bladder innovative therapy trial. J Urol. 2009;182(3):1055−1061.
Neuromodulation utilizes electrical stimulation to improve bladder function and decrease OAB symptoms. First developed in the early 1980s by McGuire and colleagues, percutaneous tibial nerve stimulation (PTNS) was approved by the FDA in 2000 as Urgent PC and provides an outpatient, nonimplantable neuromodulation alternative to medication therapy for patients with OAB.11,12 By directly stimulating the posterior tibial nerve, PTNS works via the S3 sacral nerve plexus to alter the micturition reflex and improve bladder function.
Patients were eligible for the study if they demonstrated 8 or more voids per day on a 3-day bladder diary (whether or not they had a history of previous anticholinergic drug use). A total of 100 ambulatory adults with OAB symptoms were enrolled and randomly assigned to PTNS 30-minutes per week or tolterodine ER 4 mg daily.
At 12 weeks, both groups demonstrated a significant improvement in OAB measures as well as validated symptom severity and quality-of-life questionnaire scores. Subjective assessment of improvement in OAB symptoms was significantly greater in the PTNS group than in the tolterodine group (79.5% vs 54.8%, respectively; P = .01). However, mean reduction of voids for 24 hours was not significantly different between the two groups.
Both treatments were well tolerated, with only 15% to 16% of patients in both groups reporting mild to moderate side effects. The tolterodine group did have a significantly higher risk of dry mouth; however, the risk of constipation was not significantly different between the groups.
The authors performed an important multicenter, nonblinded, randomized, controlled trial, which was one of the first trials to directly compare two OAB therapies. The generalizability of the findings were limited, as the cohort included mostly patients with dry OAB who had no objective measures on UUI episodes. In addition, this trial had a limited observation period of only 12 weeks. Information regarding the effect of treatment after cessation of weekly PTNS therapy was not examined. Therefore, we are not able to determine whether repeat sessions provide adequate maintenance in the long term.
PTNS 30 minutes daily is as effective as tolterodine ER 4 mg daily for 12 weeks in reducing OAB symptoms. PTNS is a safe alternative that should be considered in patients with OAB who poorly tolerate or have contraindications to medication therapy.
Visco AG, Brubaker L, Richter HE, et al. Anticholinergic therapy vs onabotulinumtoxinA for urgency urinary incontinence. NEJM. 2012;367(19):1803−1813.
The newest therapy for OAB is onabotulinumtoxinA, or Botox, which was FDA approved this year for the treatment of OAB in adults who cannot use or do not tolerate anticholinergic medications. Recommended doses are 100 U onabotulinumtoxinA in patients with idiopathic refractory OAB and 200 U onabotulinumtoxinA for patients with neurogenic OAB.
OnabotulinumtoxinA is a neurotoxin that blocks synaptic transmission at the neuromuscular junction to cause muscle paralysis and atrophy.13 Injecting onabotulinumtoxinA into the detrusor smooth muscle should relax the bladder and decrease sensations of urgency and frequency to achieve a longer duration of time for bladder filling and reduce the risk of urgency incontinence.
Effects of onabotulinumtoxinA appear to wear off over time, and patients may require repeat injections. Side effects of onabotulinumtoxinA therapy include an increased risk of UTI and the potential for urinary retention requiring intermittent self-catheterization.
Related article: Update on Pelvic Floor Dysfunction Autumn L. Edenfield, MD, and Cindy L. Amundsen, MD (October 2012)
The Anticholinergic Versus Botulinum Toxin Comparison (ABC) study was a multicenter, randomized, double-blind, double-placebo–controlled trial conducted in women without known neurologic disease with moderate to severe UUI (defined as >5 UUI episodes on a 3-day bladder diary). Women were randomly assigned to a single intradetrusor injection of 100 U onabotulinumtoxinA plus oral placebo or to a single intradetrusor injection of saline plus solifenacin 5 mg daily (with the option of dose escalation and then switching to trospium XR if no improvement was seen).
Of the 241 women included in the final analysis, approximately 70% in each group reported adequate control of symptoms at 6 months. Adequate control was defined as a response of “agree strongly” or “agree” to the statement: “This treatment has given me adequate control of my urinary leakage.” Women in the onabotulinumtoxinA group were significantly more likely than women in the anticholinergic medication group to report complete resolution of UUI at 6 months (27% vs 13%, P = .003). However, the mean reduction in episodes of UUI per day and the improvements in quality-of-life questionnaire scores were found to be similar. Interestingly, worse baseline UUI was associated with greater reduction in episodes of UUI for both therapies.
