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.