










































This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2021 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

Key Words Competing Interests Article Information

Overactive bladder, therapeutics, urgency 
urinary incontinence

None declared. Received on March 15, 2021 
Accepted on July 4, 2021

Soc Int Urol J.2021;2(5):311–322

DOI: 10.48083/HZVQ6675

311SIUJ.ORG SIUJ  •  Volume 2, Number 5  •  September 2021

REVIEW

Overactive Bladder: Where We Are  
and Where We Are Going
Charan S. Mohan,1 Wai Lee,1 Kathleen C. Kobashi2

1 The Arthur Smith Institute for Urology, Northwell Health, New Hyde Park, United States  
2 Section of Urology and Renal Transplantation, Virginia Mason Medical Center, Seattle, United States 

Abstract

Overactive bladder (OAB) is a heterogeneous syndrome estimated to affect approximately 10% to 15% of men and 
women globally. OAB not only negatively impacts quality of life but also results in a significant financial burden to 
both patients and health systems. Therefore, it is crucial that OAB is properly addressed. This manuscript provides a 
general review of the diagnostic algorithm for OAB and treatment per the AUA/SUFU guidelines, and an overview 
of new developments in OAB therapy. Given the wide array of therapeutic options that currently exist and those that 
are currently under development, there is tremendous opportunity to treat OAB successfully and positively affect our 
patients’ lives.

Introduction

Impact of Overactive Bladder
Overactive bladder (OAB) affects approximately 10% to 15% of men and women, with some estimates placing 
prevalence as high as 27% for men and 43% for women[1-3]. Individuals with OAB have been shown to have poorer 
quality of life, higher rates of depression, and decreased rates of sexual fulfillment when compared with individuals 
who do not have OAB[4]. In a cohort of several North American and Western European nations, OAB-related 
expenses amounted to. €1.2 billion per year[5]. With the high prevalence of OAB, the aging population, and the 
associated cost to the system, proper management of OAB is essential. This manuscript provides an overview of 
current treatment options and a discussion regarding new developments in advanced therapies.

Defining Overactive Bladder
OAB was first described as a clinical entity in the late 1980s[6]. The American Urological Association (AUA)/Society 
of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) OAB guidelines acknowledge the 
challenges in defining OAB, as reflected by the number of statements that are based upon expert opinion rather 
than scientific publications. Joint work by the International Urogynecological Association (IUGA) and International 
Continence Society (ICS) defines OAB as “urinary urgency, usually accompanied by frequency and nocturia, with 
or without urgency urinary incontinence (UUI), in the absence of urinary tract infection (UTI) or other obvious 
pathology”[7]. Figure 1 shows an algorithm proposed by the authors to guide the evaluation of patients with OAB 
symptoms. While not a guideline, this pathway can offer clinicians, particularly those not familiar with OAB 
management, a structured approach to managing these patients.

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Methods
A comprehensive literature search was performed 
using PubMed regarding (1) the pathophysiology of 
OAB, (2) treatment options for OAB, and (3) special 
considerations with respect to OAB management. 
Approach to treatment is presented per the AUA/SUFU 
guidelines, summarizing lifestyle modifications (first-
line), pharmacotherapy (second-line), and surgical and 
interventional therapies (third-line), and concluding 
with a discussion regarding new treatment developments 
in advanced therapies.

Pathophysiology
Several etiologies for OAB have been defined: (1) 
myogenic detrusor overactivity (DO), (2) overactive 
signaling by the central nervous system (CNS) causing 
micturition (neurogenic), and (3) alterations within the 
urothelium of the lower urinary tract[8,9]. The myogenic 
hypothesis attributes DO to changes within the bladder 
smooth muscle that result in increased excitability and 
spontaneous contraction[10]. In vivo tissue studies have 
suggested that structural changes within the detrusor 
muscle in OAB could allow for increased conduction of 
electrical impulses with resultant contraction among a 
large proportion of muscles cells[11].

In the neurogenic hypothesis, bladder overactivity 
is attributed to increased neuroplasticity within the 
CNS[12]. Maladaptive sensory signaling from pelvic 
sensory nerves can instigate DO and precipitate 
OAB[13]. Two neurotrophins, specifically brain-derived 

neurotrophic factor (BDNF) and nerve growth factor 
(NGF), have been implicated in OAB. These are 
modulators of neural plasticity, and individuals with 
OAB symptoms have demonstrated detectable amounts 
of these molecules in their urine[14–17]. Additionally, 
individuals with OAB exhibit varying degrees of 
functional connectivity in the cortex on functional 
MRI (f MRI) studies[18,19], and interestingly, sacral 
neuromodulation has been demonstrated to cause 
cerebral activity on fMRI[20], emphasizing the role of 
CNS function in OAB.

Regarding the urothelial hypothesis, research in 
rat models indicates that chronic urothelial injury, 
as modeled by intravesical injection of protamine 
su lfate into rats, ca n cause increased urina r y 
frequency and decreased voided volumes[21]. A related 
hypothesis postulates that OAB symptoms may also 
be urethrogenic, that is, arising from the urethra[22]. 
Specifically, low urethral tone and subsequent stress 
urinary incontinence (SUI) or contact of urine with 
the proximal urethra can stimulate the proximal 
urethral afferent nerves that can initiate micturition 
via the urethrovesical reflex and, in some cases, cause 
symptoms of OAB. Newer areas of exploration for OAB 
pathophysiology include the role of sex hormones, mood 
disorders, and the effect of the urinary microbiome[23].

OAB Treatment 
Guidelines
The AUA/SUFU OAB guidelines provide a framework 
clinicians can use to diagnose and stratify patients with 
OAB. As acknowledged in the guidelines, there is a lack 
of evidence-based publications in the current literature 
regarding the diagnosis of OAB. A clinical principle in 
the guidelines suggests that the initial evaluation for 
uncomplicated OAB requires only a thorough history 
and physical examination and a urinalysis to rule out 
conditions that may mimic OAB, such as urinary tract 
infection or malignancy. Use of adjunct tests such as urine 
cultures or post-void residuals can be incorporated as 
deemed necessary. The guidelines also clarify that UDS, 
cystoscopy, and renal imaging are not indicated in the 
initial workup. Clinicians should also consider how OAB 
symptoms may manifest in select populations, such as 
men with benign prostatic hypertrophy (BPH) or women 
with genitourinary syndrome of menopause (GSM).

The guidelines stratify OAB treatment into several 
tiers: first-line (behavioral and non-pharmacologic), 
second-line (pharmacologic t herapy), t hird-line 
(surgical and interventional therapies) and fourth-line 
(urinary diversion or bladder augmentation)[1]. This 
discussion focuses on the first 3 tiers.

Abbreviations 
AUA American Urological Association
BPH benign prostatic hypertrophy
BTX onabotulinumtoxinA
CNS central nervous system 
DO detrusor overactivity
GSM genitourinary syndrome of menopause
MRI magnetic resonance imaging
OAB overactive bladder
PRO patient-reported outcomes
RCT randomized control trial
SNM sacral neuromodulation
SUFU  Society of Urodynamics, Female Pelvic Medicine, and 

Urogenital Reconstruction
SUI stress urinary incontinence
UDS urodynamics
US ultrasound
UTI urinary tract infection
UUI urge urinary incontinence 

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FIGURE 1.  

Suggested clinical algorithm for management of OAB

Evaluation and Treatment of 
Patient with OAB Symptoms*

Complete history & physical, 
UA, urine culture

Rule out

• Cystitis (infection and non-infectious)
• Neurologic etiology
• Urinary retention
• Urologic malignancy
• Gender speci�c causes of urgency 
 (eg, BPH in men, GSM in women)
• Other 

Predominantly night time symptoms?

Rule out OSA
Lower extremity edema?

Evaluate nighttime drinking habits

No

Yes

Trial of therapy

Symptoms persist aQer trial 
of �rst- and second-line therapies?

First-line therapies
•  Lifestyle modi�cations

•  Pelvic �oor physical therapy

Second-line therapies
•  Anticholinergics
•  Beta 3 agonists

Consider ancillary 
testing

UDS
Cystoscopy
Imaging

UDS
Cystoscopy
Imaging

Third-line therapies
•  Tibial nerve stimulation

•  Intra-detrusor chemodenervation
•  Sacral neuromodulation

Symptoms persist after 
third-line therapy?

Consider ancillary testing 

Consider Fourth-line therapies
•  Bladder augmentation

•  Urinary diversion
* This is a suggested clinical algorithm 
 proposed by the authors, recognizing 
 other clinical approaches exist. 

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First-Line Therapy
First-line therapy for OAB includes low-risk behavioral 
interventions, although much of the data supporting 
t hese t herapies is drawn from non-randomized 
controlled trials (RCT). In a study of pelvic f loor 
biofeedback for OAB symptoms in women, 9 weeks of 
EMG-based biofeedback for pelvic floor muscle therapy 
resulted in significant symptom improvement[24].  
A review exploring the role of pelvic f loor muscle 
therapy traditionally used for SUI found the use of 
similar regimens in patients who had urinary urgency 
and OAB symptoms effectively reduced symptoms[25].

In a comprehensive review regarding urinar y 
symptoms in overweight and obese women, weight 
loss showed no benefit in the reduction of urinary 
urgency[26]. However, in a cohort of morbidly obese 
patients who underwent laparoscopic sleeve gastrectomy, 
patients experienced a significant improvement in OAB 
symptoms as measured by a 3-day voiding diary and 
improvement on the OAB short form questionnaire.  
The mean reduction in BMI following surgery was 
9 kg/m2, suggesting that the magnitude of weight loss 
to reduce symptoms may be unattainable for many 
patients[27].

Smoking and dietary habits, particularly consumption 
of carbonated beverages, alcohol, and caffeine, can cause 
OAB symptoms. Accordingly, lifestyle modifications 
aimed at reducing smoking and dietary triggers can result 
in an improvement of OAB[28]. Finally, an association 
between functional constipation and OAB has been 
shown[29–31], but these studies do not specifically report 
on the effect of treating constipation and relief of OAB.

Second-Line Therapy
Anticholinergics
Anticholinergics are a well-established pharmacotherapy 
for OAB[1]. There are 5 described subt y pes of 
muscarinic receptors, of which M2 and M3 are found 
in highest concentration within the bladder. While 
the M2 receptor is predominant in the bladder, the M3 
receptors are most strongly associated with micturition 
control[32]. A review examining the effectiveness of 
anticholinergics versus behavioral therapy concluded 
that anticholinergics outperformed non-pharmacologic 
interventions for improvement in OAB symptoms[33].

While dry mouth and constipation are the most 
frequent side effects of anticholinergic medications, 
cognitive side effects can be profound, particularly 
amongst older individuals. The rates of discontinuation 
of anticholinergics in trial settings have been shown to 
be as high 80%[34]. In a case– control study conducted 
in the United Kingdom, anticholinergic exposure was 
associated with dose-dependent increased odds of 
developing dementia[35]. This relationship has been well 

documented and demonstrated, particularly in older 
individuals[36–38]. At a molecular level, trospium’s 
bulky quaternary amine structure limits its penetration 
across the blood–brain barrier, thereby reducing 
unwanted cognitive effects[39,40].

Beta-3 agonists
Beta-3 agonists represent a newer class of OAB 
medication. Studies have demonstrated that mirabegron 
is equally efficacious as anticholinergics in their reduction 
of OAB symptoms[41–43]. Potential side effects include 
hypertension and cardiac arrythmia[44]. In a study 
examining the safety profile of mirabegron, there was a 
slight increase in hypertension with this drug compared 
with placebo and only among individuals over 75 (7% 
versus 5%)[45]. The absence of hypertension risk has also 
been reaffirmed on meta-analysis[46]. In an observational 
study from the UK, improvements in both quality of life 
and health status were seen for patients on mirabegron, 
with over 50% persisting on the drug at 12 months[47].

Recently approved, vibegron is a novel beta-3 agonist 
that has also shown efficacy in placebo-controlled 
studies including reduction of micturition episodes 
and urge incontinence episodes[48,49]. Furthermore, 
recent RCT data showed no difference in the rates of 
hypertension between patients on vibegron versus 
placebo[50].

Despite a higher per-pill cost of beta-3 agonists, recent 
studies have demonstrated a similar cost-effectiveness 
between beta-3 agonists and anticholinergics. This 
increased cost-effectiveness has been attributed to 
decreased discontinuation of beta-3 agonists, leading to 
improved quality of life, decreased need for third-line 
therapies, and decreased health care use due to adverse 
events[51–54]. 

Third-Line Therapy
Third-line therapies represent a rapidly growing 
category of OAB treatment, although they remain 
underutilized[55]. Existing third-line therapies include 
bladder chemodenervation with onabotulinumtoxinA 
(BTX), percutaneous tibial nerve modulation (PTNM), 
and sacral neuromodulation (SNM).

Bladder chemodenervation with 
onabotulinumtoxinA
Chemodenervation involves the prevention of pre-
synaptic release of acetylcholine (ACh) thereby averting 
excitation of ACh-dependent smooth muscle within the 
detrusor and reducing bladder contractions[56]. Data 
also suggest that the toxin may decrease sensory input 
during bladder filling via its effect on ATP-regulated 
signaling mechanisms[56–58].

BTX is administered cystoscopically with injections 
distributed throughout the bladder[59,60]. Complete 

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resolution of urinary incontinence has been shown 
to be higher amongst those receiving BTX (27%) 
compared with those on anticholinergics (13%)[61]. 
BTX also outperforms placebo for the reduction of 
OAB symptoms, with 2.95 fewer daily UUI episodes 
compared with 1 fewer observed with a placebo after 12 
weeks of treatment[58]. BTX injection also appears to be 
of therapeutic value for all patients with idiopathic OAB, 
regardless of whether DO is present on pretreatment 
urodynamics[62]. One of the potential risks of BTX is 
urinary retention. However, the definition of retention 
is not standardized across the BTX reports, and this 
has contributed to the widely variable (2% to 35%) 
rates reported in the literature. The risk of retention 
appears to be dose-dependent[63–66]. Studies have 
demonstrated a median of 7.6 months of symptom relief 
following BTX injection[67]. There are data suggesting 
that the production of neutralizing antibodies can result 
in tachyphylaxis with successive treatments with BTX. 
However, this risk has been drastically lowered with 
newer formulation of the toxin[68].

Percutaneous tibial nerve modulation 
Performed in the clinic setting, PTNM involves 12 weekly 
in-office sessions during which a 34-gauge needle is 
placed cephalad to the medial malleolus and posterior 
to the tibia. The posterior tibial nerve is stimulated 
at varying frequencies with an external generator.  
The hy pothesized mechanism of action involves 
modulation of bladder contraction via both afferent and 
efferent pathways of the tibial nerve[69,70].

PTNM has shown success in patients with refractory 
OAB. In a study of patients undergoing a 12-week 
study course, a 25% reduction in mean day time 
urinary urgency, a 35% reduction in number UUI 
episodes, and a 21% reduction in nighttime frequency 
was reported[71]. Adverse effects of PTNM are rare 
and include bruising, pain, and bleeding at the needle 
site[59]. PTNM therefore remains a well-tolerated and 
efficacious option for the treatment of OAB. Despite this, 
there remains a high drop-out rate, with retrospective 
data indicating an over 40% discontinuation rate[72], 
similar to the drop-out rates reported with BTX. Only 
40% to 60% of patients receive a second injection, with 
subsequent treatments decreasing even further[73–75].

The updated OAB guidelines include a specific 
statement that the guidelines do not represent a step-
by-step algorithm that must be followed in successive 
order. Consequently, a study that showed success with 
PTNM in drug-naïve OAB patients was of interest. In 
a single-arm study of drug-naïve OAB patients with  
>3 UUI episodes a day, 78% of patients saw a 50% 
reduction in their UUI episodes, with 40% achieving 
complete continence[76].

Sacral neuromodulation
Sacral neuromodulation is an operative procedure, 
performed in 2 stages. During the first stage, a tined 
lead connected to an external generator is inserted into 
the S3 foramina. If the patient experiences a ≥ 50% 
improvement in their symptoms during the 1 to 2 week 
trial period, a permanent impulse generator (IPG) is 
inserted into a subcutaneous pocket low back/upper 
buttock[77]. Alternatively, the first stage can be done 
in the office setting as a peripheral nerve evaluation 
with temporar y bilateral leads, with or without 
fluoroscopic guidance. If successful, the lead and IPG 
can subsequently be placed in a single procedure.

SNM has been shown to be well tolerated and more 
efficacious than standard medical therapy. In a study 
comparing SNM with anticholinergic medical therapy, 
76% of the SNM arm experienced therapeutic success 
(≥ 50% improvement) compared with 49% of the 
medical arm[78]. While the ROSETTA trial suggested 
a slight advantage of BTX over SNM in reducing OAB 
symptoms, this trial used an unconventional 200-unit 
dose of BTX, as opposed to the accepted 100 units for 
idiopathic OAB[79]. This initial advantage of BTX 
was not noted at 2 years. In the 2-year follow-up, 72% 
of patients randomized to BTX had required a second 
injection, with half of these individuals requiring a 
third[80].

In a retrospective analysis of state claims data, 
38% of all patients who undergo SNM implantation 
undergo a lead revision within 5 years of their initial 
lead implantation, approximately two-thirds for device 
malfunction and the remaining third for treatment 
failure[81]. Another consideration with SNM is magnetic 
resonance imaging (MRI) compatibility. In mid-2020, a 
full-body MRI-compatible lead became FDA-approved 
and available for implantation; patients can safely 
undergo a full-body MRI with a 1.5 or 3 Tesla magnet 
for up to 30 minutes without a rest period. However, it 
is important to consider the implications of the leads 
placed before the availability of the new leads, with 
which patients should not undergo MRI below the neck. 
A review examining neuromodulation, both PTNS and 
SNM, for OAB found that overall SNM was both well 
tolerated and effective in improving OAB symptoms. 
There are no long-term data describing PTNS success 
against SNM[82].

New technologies in third-line therapy
New chemodenervation options are being studied. Data 
suggest that chimeric alternatives to the BTX toxin, such 
as the BoNT/BMY-WW toxin have stronger affinity 
for nerve terminal binding, which modulates bladder 
effects[83]. Intravesical instillation of BTX mixed with 
hydrogel to promote a slower release of drug without 

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the need for injection has been demonstrated to be well 
tolerated in interstitial cystitis patients[84]. While BTX 
hydrogel is still in the trial phase as part of the APOLLO 
study, the potential to deliver BTX “topically” via 
urinary catheter as opposed to via cystoscopic injections 
could significantly enhance the ease of delivery[85].

New technologies for PTNM are also in development. 
The eCoin is an implantable device, approximately the 
size of a nickel, that is placed along the course of the 
patient’s posterior tibial nerve. It can be placed in the 
office setting and implantation minimizes the need 
for weekly visits. During clinical trials, 68% of subjects 
demonstrated at least 50% reduction in UUI episodes 
at 48 weeks[86]. Another investigational technology is 
the StimGuard device. An internal lead is placed near 
the posterior tibial nerve, which can be stimulated with 
an external device that remains with the patient. The 
ongoing PROTECT trial is a multicenter RCT designed 
to evaluate StimGuard for non-inferiority of versus 
traditional SNM for OAB[87].

While traditional SNM devices require a stepwise 
procedure to insert the leads and subsequently a 
permanent IPG, the AHLeveeS System from Neuspera 
Medical Inc. provides an alternative approach. This new 
device is a miniature implantable stimulator that can be 
placed into the S3 foramen and differs from the existing 
SNM technology in that in lieu of an internal IPG, the 
AHLeveeS System uses an external wireless generator. 
The use of this device in a small pilot study was seen to 
produce physiologic responses consistent with adequate 
stimulation of the S3 nerve root foramina, including 
bellows and great toe plantarflexion[88]. Table 1 shows 
the major third-line therapies and the corresponding 
emerging technologies for OAB.

Definition of Success for Interventions
As the presentation of OAB is heterogenous, defining 
success in the management of OAB can be challenging. 
A systematic review published in 2014 sought to assess 
what current research uses to define success in OAB 
trials. In this review, number of UUI episodes was the 
most common metric used to assess treatment efficacy, 
with treatment response defined as a reduction in UUI 
episodes of between 50% and 100% from baseline. Other 
symptom-based markers of treatment response were 
number of urgency episodes per day, voids per day, and 
changes in urodynamic parameters[89]. The adoption 
of patient-reported outcomes (PROs) has increased in 
biomedical and clinical research, and PRO tools are 
now more commonly used in OAB research[90,91]. 
The use of PROs as opposed to disease-oriented or 
symptom-based endpoints can provide a standardized 
means of communicating symptoms between patients 
and their physicians in the preoperative setting, thereby 
facilitating improved expectation and goal-setting 
before medical or surgical intervention for OAB[92].

Special Clinical Considerations
Nocturia
Nocturia, defined as needing to awaken at least one or 
more times per night to void, is one of the most common 
lower urinary tract symptoms (LUTS)[93]. While 
nocturia can be related to urologic disorders such as 
OAB or BPH, a variety of non-urologic conditions can 
also cause nocturia. Among these are diabetes, heart 
failure, and sleep apnea[60,93,94]. In patients with 
nocturia-predominant OAB symptoms, urologists 
should investigate possible alternative diagnoses that 
may explain a patient’s symptoms. In patients with 

TABLE 1. 

Third-line therapies for OAB and future directions

Therapy Possible Expansion

Bladder chemodenervation with onabotulinumtoxinA
Chimeric alternate molecules for BpNT/A

BTX mixed with hydrogel

Sacral neuromodulation AHLeveeS implantable generator system

Percutaneous tibial nerve modulation
 eCoin implantable device

StimGuard implantable device

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bothersome nocturia, 24-hour urine testing to evaluate 
for nocturnal polyuria should be considered, as should 
referral for sleep studies in patients who have a history of 
snoring or obstructive sleep apnea.

Considerations for Neurogenic Bladder
LUTS and OAB-like symptoms are highly prevalent in 
individuals with neurologic conditions, such as stroke 
or multiple sclerosis[95]. Up to 80% of MS patients will 
have bladder dysfunction in their lifetime, with 10% of 
all MS patients demonstrating urinary symptoms as 
the initial manifestation[96]. The approach to patients 
with neurogenic bladder can mirror the approach 
to those without neurologic disease, starting with 
first- and second-line therapies and escalating to 
advanced therapies[97]. Pharmacotherapy, particularly 
anticholinergics, have been shown eff icacious in 
managing OAB amongst those with neurogenic bladder, 
although higher doses are often required[98]. While 
BTX is the only FDA-approved therapy for neurogenic 
bladder, it should be noted that some studies have 
demonstrated that neuromodulation provides benefit to 
neurogenic patients with refractory OAB[99].

Sex Differences in Overactive Bladder 
Management
The genitourinary syndrome of menopause (GSM), 
previously referred to as vulvovaginal atrophy, refers 
to all collective genitourinary symptoms associated 
with a decreasing level of estrogen in perimenopausal 
women[100]. Twenty percent of postmenopausal women 
report severe urinary urgency, and nearly 50% of these 
women have some form of urinary incontinence[101]. 
Both topical therapies, such as vaginal estrogen, and 
non-topical options, such as selective estrogen receptor 
modulators (ospemifene and lasofoxifene in particular), 
have been shown to improve urinar y symptoms 
among women with GSM[99,100,102]. At the authors’ 

institutions, women with GSM and a history of breast 
or gynecological malignancy are frequently treated 
with local estrogen following consultation with their 
oncologist and shared-decision making with the patient.

While OAB prevalence is approximately equal 
between men and women, women are more likely to 
present with UUI[103]. As alluded to in the AUA/SUFU 
guidelines, men presenting with OAB-like symptoms 
should be screened for BPH[1]. However, OAB is still 
common among men with BPH, with up to 75% of men 
with BPH having clinical symptoms of OAB or DO 
on UDS[104]. Therefore, clinicians should consider a 
concomitant diagnosis of OAB in men with persistent 
LUTS despite treatment for BPH. In general, although 
sex-specific factors should be considered in any approach 
to OAB evaluation, treatment should be patient-specific 
based on both the presenting symptoms and patient 
goals of care.

Conclusion
OAB is a complex clinical syndrome that can have a 
serious impact on patient quality of life. From lifestyle 
modifications to implantable devices, the wide spectrum 
of available OAB therapies provides clinicians a large 
armamentarium to help alleviate OAB symptoms for 
their patients. This review explores various treatment 
modalities for OAB along with recent developments, 
with a particular emphasis on third-line therapies. 
Despite their high-efficacy rates compared to first- and 
second-line therapies, third-line treatments for OAB 
continue to be underutilized. In recent years, however, 
there has been a rapid growth and development of 
novel therapies. These new technologies allow for more 
patient-centered and tailored approaches to managing 
OAB symptoms, making it an exciting time to be a 
clinician treating OAB.

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References

1. Gormley E, Lightner D, Burgio K, Chai T, Clemens J, Culkin D, et al. 
Diagnosis and treatment of overactive bladder (non-neurogenic) in 
adults: AUA/SUFU guideline. J Urol.2012 Dec 2012;188(6 Suppl)
doi:10.1016/j.juro.2012.09.079

2. Irwin D, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, et al. 
Population-based survey of urinary incontinence, overactive bladder, 
and other lower urinary tract symptoms in five countries: results of the 
EPIC study. Eur Urol.2006 Dec;50(6)doi:10.1016/j.eururo.2006.09.019

3. Stewart W, Van Rooyen J, Cundiff G, Abrams P, Herzog A, Corey R, et 
al. Prevalence and burden of overactive bladder in the United States. 
World J Urol.2003 May 2003;20(6)doi:10.1007/s00345-002-0301-4

4. Coyne K, Sexton C, Irwin D, Kopp Z, Kelleher C, Milsom I. The 
impact of overactive bladder, incontinence and other lower urinary 
tract symptoms on quality of life, work productivity, sexuality and 
emotional well-being in men and women: results from the EPIC study. 
BJU Int.2008 Jun 2008;101(11)doi:10.1111/j.1464-410X.2008.07601.x

5. Irwin D, Mungapen L, Milsom I, Kopp Z, Reeves P, Kelleher C. The 
economic impact of overactive bladder syndrome in six Western countries.  
BJU Int.2009 Jan 2009;103(2)doi:10.1111/j.1464-410X.2008.08036.x

6. Tikkinen K, Auvinen A. Does the imprecise definition of overactive 
bladder serve commercial rather than patient interests? Eur Urol.2012 
Apr 2012;61(4)doi:10.1016/j.eururo.2011.12.013

7. Haylen B, de Ridder D, Freeman R, Swift S, Berghmans B, Lee J, et al. 
An International Urogynecological Association (IUGA)/International 
Continence Society (ICS) joint report on the terminology for female 
pelvic floor dysfunction. Int Urogynecol J.2010 Jan 2010;21(1)
doi:10.1007/s00192-009-0976-9

8. Meng E, Lin W-Y, Lee W-C, Chuang Y-C. Pathophysiology of overactive 
bladder. Low Urin Tract Symptoms.2012;4(s1):48-55. doi:https://doi.
org/10.1111/j.1757-5672.2011.00122.x

9. Wein A, Rackley R. Overactive bladder: a better understanding 
of pathophysiology, diagnosis and management. J Urol.2006 Mar 
2006;175(3 Pt 2)doi:10.1016/S0022-5347(05)00313-7

10. Brading A. A myogenic basis for the overactive bladder. Urology.1997 
Dec;50(6A Suppl)doi:10.1016/s0090-4295(97)00591-8

11. Haferkamp A, Dörsam J, Elbadawi A. Ultrastructural diagnosis 
of neuropathic detrusor overactivit y: validation of a common 
myogenic mechanism. Adv Exp Med Biol.2 0 0 3;5 3 9 (P t A )
doi:10.1007/978-1-4419-8889-8_20

12. Yoshimura N. Lower urinary tract symptoms (LUTS) and bladder 
afferent activity. Neurourol Urodyn.2007 Oct;26(6 Suppl)doi:10.1002/
nau.20487

13. O’Reilly B, Kosaka A, Knight G, Chang T, Ford A, Rymer J, et al. P2X 
receptors and their role in female idiopathic detrusor instability.  
J Urol.2002 Jan 2002;167(1).

14. Antunes-Lopes T, Pinto R, Barros SC, Botelho F, Silva CM, Cruz CD, 
et al. Urinary neurotrophic factors in healthy individuals and patients 
with overactive bladder. J Urol.2013 Jan;189(1):359-65. doi: 10.1016/j.
juro.2012.08.187. Epub 2012 Nov 19.

15. Ochodnicky P, Cruz CD, Yoshimura N, Cruz F. Neurotrophins as 
regulators of urinary bladder function. Nat Rev Urol.2012-10-09 
2012;9(11):628-637. doi:doi:10.1038/nrurol.2012.178

16. Frias B, Lopes T, Pinto R, Cruz F, Cruz C. Neurotrophins in the lower 
urinary tract: becoming of age. Curr Neuropharmacol.2011 Dec 
2011;9(4)doi:10.2174/157015911798376253

17. Antunes-Lopes T, Carvalho-Barros S, Cruz C-D, Cruz F, Martins-Silva 
C. Biomarkers in overactive bladder: a new objective and noninvasive 
tool? Adv Urol.2011. doi:https://doi.org/10.1155/2011/382431

18. Zuo L, Chen J, Wang S, Zhou Y, Wang B, Gu H. Intra- and inter-resting-
state networks abnormalities in overactive bladder syndrome patients: 
an independent component analysis of resting-state fMRI. World J 
Urol.2020 Apr 2020;38(4)doi:10.1007/s00345-019-02838-z

19. Zuo L, Zhou Y, Wang S, Wang B, Gu H, Chen J. Abnormal brain 
functional connectivity strength in the overactive bladder syndrome: 
a resting-state fMRI study. Urology.2019 Sep;131doi:10.1016/j.
urology.2019.05.019

20. Weissbart S, Bhavsar R, Rao H, Wein A, Detre J, Arya L, et al. Specific 
changes in brain activity during urgency in women with overactive 
bladder after successful sacral neuromodulation: a functional magnetic 
resonance imaging study. J Urol.2018 Aug;200(2)doi:10.1016/j.
juro.2018.03.129

21. Shioyama R, Aoki Y, Ito H, Matsuta Y, Nagase K, Oyama N, et al. 
Long-lasting breaches in the bladder epithelium lead to storage 
dysfunction with increase in bladder PGE2 levels in the rat. Am J 
Physiol Regul Integr Comp Physiol.2008 Aug;295(2):R714-8. doi: 
10.1152/ajpregu.00788.2007. Epub 2008 Jun 11.

22. Jung S, Fraser M, Ozawa H, Yokoyama O, Yoshiyama M, De 
Groat W, et al. Urethral af ferent ner ve activit y af fects the 
micturition reflex; implication for the relationship between stress 
incontinence and detrusor instability. J Urol.1999 Jul 1999;162(1)
doi:10.1097/00005392-199907000-00069

23. Peyronnet B, Mironska E, Chapple C, Cardozo L, Oelke M, 
Dmochowski R, et al. A comprehensive review of overactive bladder 
pathophysiology: on the way to tailored treatment. Eur Urol.2019 Jun 
2019;75(6)doi:10.1016/j.eururo.2019.02.038

24. Voorham J, De Wachter S, Van den Bos T, Putter H, Lycklama À 
Nijeholt G, Voorham-van der Zalm P. The effect of EMG biofeedback 
assisted pelvic floor muscle therapy on symptoms of the overactive 
bladder syndrome in women: a randomized controlled trial. Neurourol 
Urodyn.2017 Sep 2017;36(7)doi:10.1002/nau.23180

318 SIUJ  •  Volume 2, Number 5  •  September 2021 SIUJ.ORG

REVIEW

http://SIUJ.org


25. Burgio K. Update on behavioral and physical therapies for incontinence 
and overactive bladder: the role of pelvic floor muscle training. Curr 
Urol Rep.2013;14(5)doi:10.1007/s11934-013-0358-1

26. Yazdany T, Jakus-Waldman S, Jeppson P, Schimpf M, Yurteri-Kaplan 
L, Ferzandi T, et al. American Urogynecologic Society systematic 
review: the impact of weight loss intervention on lower urinary tract 
symptoms and urinary incontinence in overweight and obese women. 
Female Pelvic Med Reconstr Surg.Jan/Feb 2020;26(1)doi:10.1097/
SPV.0000000000000802

27. Palleschi G, Pastore A, Rizzello M, Cavallaro G, Silecchia G, Carbone 
A. Laparoscopic sleeve gastrectomy effects on overactive bladder 
symptoms. J Surg Res.2015;196(2)doi:10.1016/j.jss.2015.03.035

28. Dallosso H, McGrother C, Matthews R, Donaldson M. The association 
of diet and other lifestyle factors with overactive bladder and stress 
incontinence: a longitudinal study in women. BJU Int.2003 Jul 
2003;92(1)doi:10.1046/j.1464-410x.2003.04271.x

29. Coyne KS, Cash B, Kopp Z, Gelhorn H, Milsom I, Berriman S, et al. 
The prevalence of chronic constipation and faecal incontinence 
among men and women with symptoms of overactive bladder. BJU 
Int.2011;107(2):254-61. doi: 10.1111/j.1464-410X.2010.09446.x

30. Maeda T, Tomita M, Nakazawa A, Sakai G, Funakoshi S, Komatsuda 
A, et al. female functional constipation is associated with overactive 
bladder symptoms and urinary incontinence. Biomed Res Int.2017. 
doi:https://doi.org/10.1155/2017/2138073

31. Abreu GE, Dourado ER, Alves DN, Araujo MQ, Mendonça NSP, Barroso 
Junior U. Functional constipation and overactive bladder in women: a 
population-based study. Arq Gastroenterol.2018 Nov;55Suppl 1(Suppl 
1):35-40. doi: 10.1590/S0004-2803.201800000-46.

32. Andersson K. Antimuscarinics for treatment of overactive bladder. 
Lancet Neurol.2004 Jan;3(1)doi:10.1016/s1474-4422(03)00622-7

33. Alhasso A, McKinlay J, Patrick K, Stewart L. Anticholinergic drugs 
versus non-drug active therapies for overactive bladder syndrome in 
adults. Cochrane Database Syst Rev.2006;(4)doi:10.1002/14651858.
CD003193.pub3

34. Sexton CC, Notte SM, Maroulis C, Dmochowski RR, Cardozo L, 
Subramanian D, et al. Persistence and adherence in the treatment 
of overactive bladder syndrome with anticholinergic therapy: a 
systematic review of the literature. Int J Clin Pract.2011 May;65(5)
doi:10.1111/j.1742-1241.2010.02626.x

35. Coupland CAC, Division of Primary Care UoN, Nottingham, England, 
Hill T, et al. Anticholinergic drug exposure and the risk of dementia: a 
nested case-control study. JAMA Intern Med.2020;179(8):1084-1093. 
doi:10.1001/jamainternmed.2019.0677

36. Carrière I, Fourrier-Reglat A, Dartigues J, Rouaud O, Pasquier F, Ritchie 
K, et al. Drugs with anticholinergic properties, cognitive decline, and 
dementia in an elderly general population: the 3-city study. Arch 
Internal Med.2009;169(14):1317–1324. doi:10.1001/archinternmed.

37. Jessen F, Kaduszkiewicz H, Daerr M, Bickel H, Pentzek M, Riedel-Heller 
S, et al. Anticholinergic drug use and risk for dementia: target for 
dementia prevention. Eur Arch Ppsychiatry Clin Neurosci.2010 Nov; 
260 (Suppl 2): S111-5. doi:10.1007/s00406-010-0156-4

38. Gray S, Anderson M, Dublin S, Hanlon J, Hubbar R, Walker R, et al. 
Cumulative use of strong anticholinergic medications and incident 
dementia. JAMA Intern Med.2015;175(3):401-407.

39. Staskin D. Trospium chloride: distinct among other anticholinergic 
agents available for the treatment of overactive bladder. Urol Clin 
North Am.2006 Nov;33(4)doi:10.1016/j.ucl.2006.06.006

40. Geller E, Dumond J, Bowling J, Khandelwal C, Wu J, Busby-Whitehead 
J, et al. Effect of trospium chloride on cognitive function in women 
aged 50 and older: a randomized trial. Female Pelvic Med Reconstr 
Surg.Mar/Apr 2017;23(2)doi:10.1097/SPV.0000000000000374

41. Chapple C, Cardozo L, Nitti V, Siddiqui E, Michel M. Mirabegron in 
overactive bladder: a review of efficacy, safety, and tolerability. 
Neurourol Urodyn.2014 Jan;33(1)doi:10.1002/nau.22505

42. Kuo H, Lee K, Na Y, Sood R, Nakaji S, Kubota Y, et al. Results of a 
randomized, double-blind, parallel-group, placebo- and active-
controlled, multicenter study of mirabegron, a β3-adrenoceptor 
agonist, in patients with overactive bladder in Asia. Neurourol 
Urodyn.2015 Sep;34(7)doi:10.1002/nau.22645

43. Wagg A, Cardozo L, Nitti V, Castro-Diaz D, Auerbach S, Blauwet M, 
et al. The efficacy and tolerability of the β3-adrenoceptor agonist 
mirabegron for the treatment of symptoms of overactive bladder in 
older patients. Age Ageing.2014 Sep;43(5)doi:10.1093/ageing/afu017

44. Cui Y, Zong H, Yang C, Yan H, Zhang Y. The efficacy and safety of 
mirabegron in treating OAB: a systematic review and meta-analysis 
of phase III trials. Int Urol Nephrol.2014 Jan;46(1)doi:10.1007/
s11255-013-0509-9

45. Chapple C, Cruz F, Cardozo L, Staskin D, Herschorn S, Choudhury N, et 
al. Safety and efficacy of mirabegron: analysis of a large integrated 
clinical trial database of patients with overactive bladder receiving 
mirabegron, antimuscarinics, or placebo. Eur Urol.2020 Jan;77(1)
doi:10.1016/j.eururo.2019.09.024

46. Chen H, Chen T, Chang H, Juan Y, Huang W, Pan H, et al. Mirabegron 
is alternative to antimuscarinic agents for overactive bladder without 
higher risk in hypertension: a systematic review and meta-analysis. 
World J Urol.2018 Aug;36(8)doi:10.1007/s00345-018-2268-9

47. Foley S, Choudhury N, Huang M, Stari A, Nazir J, Freeman R. Quality 
of life in patients aged 65 years and older with overactive bladder 
treated with mirabegron across eight European countries: secondary 
analysis of BELIEVE. Int J Urol. 2019 Sep;26(9)doi:10.1111/iju.14050

319SIUJ.ORG SIUJ  •  Volume 2, Number 5  •  September 2021

Overactive Bladder: Where We Are and Where We Are Going

http://SIUJ.org


48. Shi H, Chen H, Zhang Y, Cui Y. The efficacy and safety of vibegron in 
treating overactive bladder: A systematic review and pooled analysis 
of randomized controlled trials. Neurourol Urodyn.2020 Jun;39(5)
doi:10.1002/nau.24387

49. Yoshida M, Takeda M, Gotoh M, Nagai S, Kurose T. Vibegron, a novel 
potent and selective β3-adrenoreceptor agonist, for the treatment of 
patients with overactive bladder: a randomized, double-blind, placebo-
controlled phase 3 study. Eur Urol.2018 May;73(5)doi:10.1016/j.
eururo.2017.12.022

50. Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Paul N, et al. 
International phase iii, randomized, double-blind, placebo and active 
controlled study to evaluate the safety and efficacy of vibegron in 
patients with symptoms of overactive bladder: EMPOWUR.J Urol.2020 
Aug;doi:10.1097/JU.0000000000000807

51. Nazir J, Maman K, Neine M, Briquet B, Odeyemi I, Hakimi Z, et al. Cost-
effectiveness of mirabegron compared with antimuscarinic agents for 
the treatment of adults with overactive bladder in the United Kingdom. 
Value Health.2015 Sep;18(6)doi:10.1016/j.jval.2015.05.011

52. Wielage R, Perk S, Campbell N, Klein T, Posta L, Yuran T, et 
al. Mirabegron for the treatment of overactive bladder: cost-
effectiveness from US commercial health-plan and Medicare 
Advantage perspectives. J Med Econ.2016 Dec;19(12)doi:10.1080/1
3696998.2016.1204307

53. Perk S, Wielage R, Campbell N, Klein T, Perkins A, Posta L, et al. 
Estimated budget impact of increased use of mirabegron, a novel 
treatment for overactive bladder. J Manag Care Spec Pharm.2016 
Sep;22(9)doi:10.18553/jmcp.2016.22.9.1072

54. Fogaing C, Mossa A, Campeau L. Are beta 3 adrenergic agonists now 
the preferred pharmacologic management of overactive bladder? Curr 
Urol Rep.2020;21(12):49. doi:10.1007/s11934-020-01003-z

55. Moskowitz D, Adelstein S, Lucioni A, Lee U, Kobashi K. Use of third line 
therapy for overactive bladder in a practice with multiple subspecialty 
providers-are we doing enough? J Urol.2018 Mar 2018;199(3)
doi:10.1016/j.juro.2017.09.102

56. Vianello A, Proietti S, Giannantoni A. Effect of botulinum neurotoxin 
on the urinary bladder: novel insights on mechanism of action. Minerva 
Urol Nefrol.2010 Sep;62(3):259–271.

57. Dolly J, A ok i K . T he s t r uc t ur e and mo de of ac tion of 
dif ferent botulinum toxins. Eur J Neurol. 2006 Dec;13 Suppl 
4doi:10.1111/j.1468-1331.2006.01648.x

58. Collins V, Daly D, Liaskos M, McKay N, Sellers D, Chapple C, et al. 
OnabotulinumtoxinA significantly attenuates bladder afferent nerve 
firing and inhibits ATP release from the urothelium. BJU Int.2013 
Nov;112(7)doi:10.1111/bju.12266

59. Emami M, Shadpour P, Kashi A, Choopani M, Zeighami M. 
Abobotulinum - a toxin injection in patients with refractory idiopathic 
detrusor overactivity: injections in detrusor, trigone and bladder neck 
or prostatic urethra, versus detrusor - only injections. Int Braz J Urol. 
Nov-Dec 2017;43(6)doi:10.1590/S1677-5538.IBJU.2016.0622

60. Lowenstein L, Kenton K, Brubaker L, Pillar G, Undevia N, Mueller E, 
et al. The relationship between obstructive sleep apnea, nocturia, 
and daytime overactive bladder syndrome in women. Am J Obstet 
Gynecol.2008 May;198(5)doi:10.1016/j.ajog.2008.02.024

61. Visco A, Brubaker L, Richter H, Nygaard I, Paraiso MFR, Menefee SA, et 
al. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary 
incontinence. N Engl J Med.2012;367(19):1803–1813. doi:10.1056/
NEJMoa1208872

62. Rovner E, Kennelly M, Schulte-Baukloh H, Zhou J, Haag-Molkenteller 
C, Dasgupta P. Urodynamic results and clinical outcomes with 
intradetrusor injections of onabotulinumtoxinA in a randomized, 
placebo-controlled dose-finding study in idiopathic overactive bladder. 
Neurourol Urodyn.2011 Apr;30(4)doi:10.1002/nau.21021

63. Osborn DJ, Kaufman MR, Mock S, Guan MJ, Dmochowski RR, Reynolds 
WS. Urinary retention rates after intravesical onabotulinumtoxinA 
injection for idiopathic overactive bladder in clinical practice and 
predictors of this outcome. Neurourol Urodyn.Sep 2015;34(7):675-8. 
doi:10.1002/nau.22642

64. Flynn MK, Amundsen CL, Perevich M, Liu F, Webster GD. Outcome of 
a randomized, double-blind, placebo controlled trial of botulinum A 
toxin for refractory overactive bladder. J Urol.Jun 2009;181(6):2608-15. 
doi:10.1016/j.juro.2009.01.117

65. Dmochowski R, Chapple C, Nitti V, Chancellor M, Everaer t K, 
Thompson C, et al. Efficacy and safety of onabotulinumtoxinA for 
idiopathic overactive bladder: a double-blind, placebo controlled, 
randomized, dose ranging trial. J Urol.2010 Dec;184(6)doi:10.1016/j.
juro.2010.08.021

66. Dowson C, Watkins J, Khan M, Dasgupta P, Sahai A. Repeated 
botulinum toxin type A injections for refractory overactive bladder: 
medium-term outcomes, safety profile, and discontinuation rates. Eur 
Urol.2012 Apr;61(4)doi:10.1016/j.eururo.2011.12.011

67. Nitti V, Ginsberg D, Sievert K, Sussman D, Radomski S, Sand P, et 
al. Durable efficacy and safety of long-term onabotulinumtoxina 
treatment in patients with overactive bladder syndrome: final results of 
a 3.5-year study. J Urol.2016 Sep;196(3)doi:10.1016/j.juro.2016.03.146

68. Patel A, Patterson J, Chapple C. Botulinum toxin injections for 
neurogenic and idiopathic detrusor overactivity: a critical analysis 
of results. Eur Urol.2006 Oct;50(4)doi:10.1016/j.eururo.2006.07.022

69. Statskin D, Peter K, MacDiarmid S, Shore N, deGroat WC. Percutaneous 
tibial nerve stimulation: a clinically and cost effective addition to the 
overactive bladder algorithm of care. Curr Urol Rep.2012;13(5):327-334.

70. Gaziev G, Topazio L, Iacovelli V, Asimakopoulos A, Di Sant A, De Nunzio 
C, et al. Percutaneous tibial nerve stimulation (PTNS) efficacy in the 
treatment of lower urinary tract dysfunctions: a systematic review. 
BMC Urol.2013;13(61)

71. Govier F, Litwiller S, Nitti V, Kreder K, Rosenblatt P. Percutaneous 
afferent neuromodulation for the refractory overactive bladder: results 
of a multicenter study. J Urol.2001 Apr;165(4):1193–1198. DOI: https://
doi.org/10.1016/S0022-5347(05)66469-5

320 SIUJ  •  Volume 2, Number 5  •  September 2021 SIUJ.ORG

REVIEW

http://SIUJ.org


72. Te Dorsthorst M, Heesakkers J, van Balken M. Long-term real-life 
adherence of percutaneous tibial nerve stimulation in over 400 
patients. Neurourol Urodyn.2020 Feb;39(2)doi:10.1002/nau.24254

73. Eldred-Evans D, Sahai A. Medium- to long-term outcomes of botulinum 
toxin A for idiopathic overactive bladder. Therapeutic Adv Urol.2017 
Jan;9(1)doi:10.1177/1756287216672180

74. Lee W, Du C, Donahue R, Lucioni A, Kobashi K, Lee U. Majority of 
onabotulinumtoxina-naive patients with idiopathic overactive bladder 
do not repeat chemodenervation: factors affecting patient dropout 
after initial treatment with 100 units. J Urol.2020;203(4S).

75. Tam J, Nguyen A, Du C, Wang Q, Hung M, Weissbart S, et al. Patients 
have poor compliance with repeat onabotulinumtoxin a injections for 
overactive bladder. Presented at: AUA 2018, May 19; San Francisco. 
J Urol.2018;199(4S, Suppl):e646-e647. Available at: https://www.
auajournals.org/doi/pdf/10.1016/j.juro.2018.02.1549. Accessed July 
31, 2021.

76. Kobashi K, Nitti V, Margolis E, Sand P, Siegel S, Khandwala S, et al. A 
prospective study to evaluate efficacy using the nuro percutaneous 
tibial neuromodulation system in drug-naïve patients with overactive 
bladder syndrome. Urology.2019 Sep 2019;131doi:10.1016/j.
urology.2019.06.002

77. Hubsher C, Jansen R, Riggs D, Jackson B, Zaslau S. Sacral nerve 
stimulation for neuromodulation of the lower urinary tract. Canadian 
J Urol.2012;19(5):6480-6484.

78. Siegel S, Noblett K, Mangel J, Griebling T, Sutherland S, Bird E, et al. 
Results of a prospective, randomized, multicenter study evaluating 
sacral neuromodulation with InterStim therapy compared to standard 
medical therapy at 6-months in subjects with mild symptoms of 
overactive bladder. Neurourol Urodyn.2015 Mar;34(3)doi:10.1002/
nau.22544

79. Amundsen C, Richter H, Menefee S, Komesu Y, Arya L, Gregory W, 
et al. OnabotulinumtoxinA vs sacral neuromodulation on refractory 
urgency urinary incontinence in women: a randomized clinical trial. 
JAMA.2016;316(13)doi:10.1001/jama.2016.14617

80. Amundsen C, Komesu Y, Chermansky C, Gregor y W, Myers D, 
Honeycutt E, et al. Two-year outcomes of sacral neuromodulation 
versus onabotulinumtoxina for refractor y urgency urinar y 
incontinence: a randomized trial. Eur Urol.2018 Jul;74(1)doi:10.1016/j.
eururo.2018.02.011

81. Chughtai B, Thomas D, Sun T, Sedrakyan A. Failures of sacral 
neuromodulation for incontinence. JAMA Surg.2018;153(5)doi:10.1001/
jamasurg.2017.6093

82. Tutolo M, Ammirati E, Heesakkers J, Kessler T, Peters K, Rashid T, et al. 
Efficacy and safety of sacral and percutaneous tibial neuromodulation 
in non-neurogenic lower urinary tract dysfunction and chronic pelvic 
pain: a systematic review of the literature. Eur Urol.2018 Mar;73(3)
doi:10.1016/j.eururo.2017.11.002

83. Thaker H, Zhang S, Diamond D, Dong M. Beyond botulinum neurotoxin 
A for chemodenervation of the bladder. Curr Opin Urol.2021;1;31(2):140-
146. DOI:10.1097/MOU.0000000000000843

84. Rappaport Y, Zisman A, Jeshurun-Gutshtat M, Gerassi T, Hakim G, 
Vinshtok Y, et al. Safety and feasibility of intravesical instillation of 
botulinum toxin-a in hydrogel-based slow-release delivery system in 
patients with interstitial cystitis-bladder pain syndrome: a pilot study. 
Urology.2018 Apr;114doi:10.1016/j.urology.2017.12.028

85. ClinicalTrials.gov. APOLLO: the study of an investigational drug, 
patisiran (ALN-T TR02), for the treatment of transthyretin (T TR)-
mediated amyloidosis. Full text view. 2021. Available at: https://
clinicaltrials.gov/ct2/show/NCT01960348. Accessed July 31, 2021.

86. Rogers A, Bragg S, Ferrante K, Thenuwara C, Peterson D. Pivotal 
study of leadless tibial nerve stimulation with eCoin ® for urgency 
urinary incontinence: an open-label, single arm trial. J Urol.2021 
Aug;206(2):399-408. doi: 10.1097/JU.0000000000001733.

87. ClinicalTrials.gov. CAN-Stim compared to SNS in treatment of urinary 
urgency incontinence with wireless neuromodulation technology - full 
text view - clinicaltrials.gov. Available at: https://clinicaltrials.gov/ct2/
show/NCT02577302. Accessed July 30, 2021.

88. van Kerrebroeck P, Reekmans M, van Koeveringe G, Yeh A, Fayram T, 
Sharan A, et al. First-in-human implantation of a mid-field powered 
neurostimulator at the sacral nerve: results from an acute study. 
Neurourol Urodyn.2019 Aug;38(6)doi:10.1002/nau.24035

89. Goldman H, Wyndaele J, Kaplan S, Wang J, Ntanios F. Defining 
response and non-response to treatment in patients with overactive 
bladder: a systematic review. Curr Med Res Opin.2014 Mar;30(3)doi:
10.1185/03007995.2013.860021

90. Deshpande PR, Rajan S, Sudeepthi BL, Abdul Nazir CP. Patient-reported 
outcomes: a new era in clinical research. Perspect Clin Res.2011 
Oct;2(4):137-44. doi: 10.4103/2229-3485.86879. PMID: 22145124; 
PMCID: PMC3227331.

91. Speight J, Barendse S. FDA guidance on patient reported outcomes. 
BMJ.2010;340:c2921. doi: 10.1136/bmj.c2921.

92. Marschall-Kehrel D, Roberts R, Brubaker L. Patient-reported outcomes 
in overactive bladder: the influence of perception of condition and 
expectation for treatment benefit. Urology.2006 Aug;68(2 Suppl)
doi:10.1016/j.urology.2006.02.046

93. Weiss JP. Nocturia: focus on etiology and consequences. Rev 
Urol.2012;14(3-4):48-55.

94. Arslan B, Gezmis C, Çetin B, Gönültas S, Gökmen E, Gürkan O, et al. Is 
obstructive sleep apnea syndrome related to nocturia? Low Urin Tract 
Symptoms.2019 May;11(3)doi:10.1111/luts.12250

321SIUJ.ORG SIUJ  •  Volume 2, Number 5  •  September 2021

Overactive Bladder: Where We Are and Where We Are Going

http://SIUJ.org


95. Wein A, Dmochowski R. Neuromuscular dysfunction of the lower urinary 
tract. In: Partin A, Peters C, Kavoussi L, Dmchowski R, Wein A, eds. 
Campbell Walsh Wein Urology. Elsevier; 2020.

96. Aharony S, Lam O, Corcos J. Evaluation of lower urinary tract symptoms 
in multiple sclerosis patients: Review of the literature and current 
guidelines. Can Urol Assoc J.2017;11:61-64.

97. Kurpad R, Kennelly M. The evaluation and management of refractory 
neurogenic overactive bladder. Curr Urol Rep.2014 Oct;15(10)
doi:10.1007/s11934-014-0444-z

98. Kennelly M, Devoe W. Overactive bladder: pharmacologic treatments 
in the neurogenic population. Rev in urology.2008;10(3).

99. Sanford M, Suskind A. Neuromodulation in neurogenic bladder. Transl 
Androl Urol.2016 Feb;5(1)doi:10.3978/j.issn.2223-4683.2015.12.01

100. Portamn D, LS Gass M, Panel VATCC. Genitourinary syndrome of 
menopause: new terminology for vulvovaginal atrophy from the 
International Society for the Study of Women's Sexual Health and 
the North American Menopause Society. J Sex Med.2014 Dec;11(12)
doi:10.1111/jsm.12686

101. Kim H, Kang S, Chung Y, Kim J, Kim M. The recent review of 
the genitourinar y syndrome of menopause. J Menopausal 
Med.2015;21(2):65-71. doi:10.6118/jmm.2015.21.2.65

102. Schiavi M, Sciuga V, Giannini A, Vena F, D’oria O, Prata G, et al. 
Overactive bladder syndrome treatment with ospemifene in 
menopausal patients with vulvovaginal atrophy: improvement of 
sexuality? Gynecol Endocrinol.2018 Aug;34(8)doi:10.1080/0951359
0.2018.1441398

103. Eapen R, Radomski S. Gender differences in overactive bladder. Can 
J Urol.2016 Feb 2016;23(Suppl 1):2–9.

104. Dmochowski R. Overactive bladder in males. Therapeutic Adv 
Urol.2009;1(4):209-221.

322 SIUJ  •  Volume 2, Number 5  •  September 2021 SIUJ.ORG

REVIEW

http://SIUJ.org



