The Benefits of Adding Non-Antimuscarinic Pharmaceuticals in Combination With Beta-3 Agonists for Overactive Bladder Treatment: A Systematic Review

Introduction
Antimuscarinics, as the current first-line pharmacologic therapies for overactive bladder, exhibit low patient adherence and high rates of reported side effects. As a modern alternative pharmaceutical treatment, beta-3 agonists, which relax the urinary bladder, may be more tolerable for patients, increasing adherence and prescription compliance. Of interest is the growing potential for non-antimuscarinics to be incorporated in combination therapies alongside these beta-3 agonists.

Methods
Following PRISMA guidelines, searches were undertaken in PubMed, EMBASE and Cochrane Library for randomized controlled trials of patients with OAB, comparing monotherapy beta-3 agonist with beta-3 in combination with non-antimuscarinic pharmaceuticals. Risk of bias was performed using the Cochrane Risk of Bias Tool 1.

Result
Seven trials with 719 participants were included. All studies utilized mirabegron as the beta-3 agonist. Two studies analyzed the effectiveness of mirabegron in combination with a second-line treatment, whereas the other five combined third-line treatment options. Benefits were reported in studies where beta-3 agonists were used in conjunction with botulinum toxin, acupuncture, nerve stimulation, tadalafil, and vitamin D3.

Conclusion
There appear to be therapeutic benefits supporting the use of several different interventions in combination with a beta-3 agonist for the alleviation of overactive bladder symptoms. However, further research is needed due to limited evidence and heterogeneity.