Efficacy of overactive neurogenic bladder treatment: A systematic review of randomized controlled trials

Abstract

Background: Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson’s disease (PD), stroke. Objective: The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder. Materials and methods: We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022. Results: A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups. Conclusions: The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.

An individual participant meta‐analysis of mirabegron in multiple sclerosis and spinal cord injury

“…The improvement in all urodynamic parameters that we evaluated (other than compliance) challenge the conclusion of prior systematic reviews which have stated that mirabegron does not improve urodynamic parameters in this patient population 10 and metanalyses which have not shown significant results. 11 While our results show a significant improvement, it is important to realize this a group-level response; individual patients may experience different degrees of improvement in their symptoms and urodynamic outcomes with mirabegron, and an individualized approach is necessary for the management of patients. Second, our results are relevant in the era of cognitive concerns associated with OAB anticholinergic medications, and the wish by many providers 21 and patients 22 to avoid these medications.…”

“…We used the following inclusion criteria to identify studies for this IPDMA: study design was a randomized, placebo-controlled clinical trial; study population was people with MS or SCI, intervention was mirabegron or placebo, and outcomes included at least one urodynamic variable. Recent systematic reviews were assessed, [9][10][11] and we repeated their search strategies in August 2022 and identified two studies that fit our inclusion criteria: Welk et al 15 and Krhut et al, 14 both published in 2018.…”

“…As such, there are only limited placebo‐controlled randomized trials that have been published. While authors have published systematic reviews and meta‐analyses of clinical trial results, 9–11 there have been no individual patient data meta‐analyses (IPDMA); advantages of combining participant level data are increased statistical power, standardized analysis, improved data quality, and avoidance of ecological bias in subgroup analysis 12 . They are considered the gold standard of meta‐analysis, but are often not done as they are more resource intensive than study‐level meta‐analyses 13 .…”

Identification of brain functional connectivity during acute transcutaneous tibial nerve stimulation: A 3T fMRI study

“…Depending on the localization and the extent of the underlying disease or lesion, various patterns of NLUTD will occur 4 . Tibial nerve stimulation (TNS) might be an effective therapeutic intervention to improve NLUTD 5 , as recent studies examining urinary problems associated with Parkinson's disease have shown 6,7 . This therapy is applied using a surface electrode at the ankle and actively stimulating 20–30 min/day.…”

“…4 Tibial nerve stimulation (TNS) might be an effective therapeutic intervention to improve NLUTD 5 , as recent studies examining urinary problems associated with Parkinson's disease have shown. 6,7 This therapy is applied using a surface electrode at the ankle and actively stimulating 20-30 min/day. The stimulation period required to induce a long-lasting modulating clinical effect is 3 months, having greater therapeutic durability than intermittent acute therapy alone.…”