Combination therapy in overactive bladder‐untapped research opportunities: A systematic review of the literature

Abstract

Aims Overactive bladder (OAB) affects over 17% of the population and significantly effect the health‐related quality of life. The treatments for OAB include first line (lifestyle modification, pelvic floor muscle training), second line (anticholinergic or beta‐3 agonist medications), and third line therapies (intradetrusor botulinum toxin injection, sacral neurostimulation [SNM], or percutaneous tibial nerve stimulation [PTNS]). For those with urinary incontinence secondary to OAB, complete continence is the goal of therapy, though cure rates are only 5% to 40%. The use of combination therapies can be employed in refractory OAB, however, the efficacy of pooled modalities is relatively unknown. Our objective was to determine the volume of data supporting combination therapy in treating OAB. Methods We systematically reviewed PubMed, EMBASE, the Cochrane Library, and Google Scholar for articles published before October 2018. Each was independently reviewed by two reviewers and examined in detail if they met inclusion criteria. Results A total of 32 studies met inclusion criteria and were reviewed. Most large prospective studies evaluated combinations of medications with behavioral therapy or medications together. Combination therapy studies of third‐line treatments were rare and centered on medication with PTNS. No studies examined intradetrusor botulinum toxin injections in combination with another therapy and only one retrospective study briefly examined SNM therapy in combination with medication. Conclusion Combination therapy, with certain first, second, and third‐line OAB therapies, appears to be efficacious. There is a further need for carefully designed combination therapy studies, particularly those including third line modalities.

Trigonal-Sparing vs. Trigonal-Involved OnabotulinumtoxinA Injection for the Treatment of Overactive Bladder: A Systematic Review and Meta-Analysis

“…Due to less effectiveness and poor adherence to first and second-line treatments, the main objective is the search for new treatments in OAB therapy. Nowadays, literature research reveals that BoNT-A intravesical injection was recommended as a third-line treatment of OAB (26,27). Intravesical BoNT-A injections may represent a treatment modality for patients with NDO and IDO.…”

Adding mirabegron after intravesical onabotulinumtoxinA injection improves therapeutic effects in patients with refractory overactive bladder

“…Combination therapy modalities are commonly and increasingly used in several medical conditions (such as refractory DM, hypertension, cancer, and refractory OAB) 6,14 . Before the beta‐3 agonist era, several studies using a combination of two anticholinergic agents have shown that combination therapy significantly reduced urgency and UUI compared with monotherapy with each drug 15 . Recently, an interesting study escalated the second antimuscarinic dose in patients with refractory OAB on monotherapy with the first anticholinergic drug 16 .…”

“…Few studies have investigated the efficacy and safety of medication (mainly anticholinergics) in combination with nonpharmacological treatment in OAB patients. A systematic review showed that bladder training combined with anticholinergic drugs demonstrated controversial results about its superiority over monotherapy 15 . Four prospective, small group studies found that posterior tibial nerve stimulation with medication improved OAB symptoms compared with either type of monotherapy.…”

Botox rechallenge—An additional tool in the management of an incompletely emptying bladder and inadequate overactive symptom control following sacral neuromodulation

“…9,10 Although adjunct pharmacotherapy may supplement the efficacy of SNM, there are currently no published descriptions of addition of BoNT-A therapy following implantation of an SNM device-although it is being used anecdotally. 11,12 We present two DO-DU patients where previous BoNT-A therapy led to AUR who were successfully rechallenged with BoNT-A following implantation of an Interstim II device (Medtronic, Minneapolis, Minnesota) which had failed to give adequate control to OAB symptoms.…”

“…Previously called detrusor hyperactivity with impaired contractility (DHIC), patients with detrusor overactivity and detrusor underactivity (DO‐DU) are best served by sacral neuromodulation (SNM) as it adds to OAB symptom control while improving bladder underactivity 9,10 . Although adjunct pharmacotherapy may supplement the efficacy of SNM, there are currently no published descriptions of addition of BoNT‐A therapy following implantation of an SNM device—although it is being used anecdotally 11,12 …”