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AUA/SUFU Guideline
DIAGNOSIS AND TREATMENT OF OVERACTIVE
BLADDER (Non-Neurogenic) IN ADULTS:
AUA/SUFU GUIDELINE
E. Ann Gormley, Deborah J. Lightner, Kathryn L. Burgio, Toby C. Chai, J. Quentin
Clemens, Daniel J. Culkin, Anurag Kumar Das, Harris Emilio Foster, Jr., Harriette
Approved by the AUA Miles Scarpero, Christopher D. Tessier, Sandip Prasan Vasavada
Board of Directors
May 2014
Authors’ disclosure of
Purpose: The purpose of this guideline is to provide a clinical framework for the
potential conflicts of diagnosis and treatment of non-neurogenic overactive bladder (OAB).
interest and author/staff
contributions appear at Methods: The primary source of evidence for the original version of this guideline
the end of the article. was the systematic review and data extraction conducted as part of the Agency for
© 2014 by the American Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment
Urological Association Number 187 titled Treatment of Overactive Bladder in Women (2009).1 That
report searched PubMed, MEDLINE, EMBASE, and CINAHL for English-language
studies published from January 1966 to October 2008 relevant to OAB. AUA
conducted additional literature searches to capture treatments not covered in
detail by the AHRQ report (e.g., intravesical onabotulinumtoxinA) and relevant
articles published between October 2008 and December 2011. Insufficient
evidence was retrieved regarding diagnosis; this portion of the guideline,
therefore, is based on Clinical Principles and Expert Opinion. The review yielded
an evidence base of 151 treatment articles after application of inclusion/exclusion
criteria. The AUA update literature review process, in which an additional
systematic review is conducted periodically to maintain guideline currency with
newly-published relevant literature, was conducted in February 2014. This review
identified an additional 72 articles relevant to treatment. These publications were
used to create the majority of the treatment portion of the guideline. When
sufficient evidence existed, the body of evidence for a particular treatment was
assigned a strength rating of A (high), B (moderate) or C (low). Additional
treatment information is provided as Clinical Principles and Expert Opinion when
insufficient evidence existed. See text and algorithm for definitions and detailed
diagnostic, management and treatment frameworks.

Guideline Statements

Diagnosis:

1. The clinician should engage in a diagnostic process to document symptoms and

signs that characterize OAB and exclude other disorders that could be the
The Panel would like to
acknowledge Martha M. cause of the patient’s symptoms; the minimum requirements for this process
Faraday, Ph.D., for her are a careful history, physical exam, and urinalysis. Clinical Principle
methodological expertise
and invaluable 2. In some patients, additional procedures and measures may be necessary to
contributions as well as validate an OAB diagnosis, exclude other disorders and fully inform the
the Vanderbilt Evidence-
treatment plan. At the clinician’s discretion, a urine culture and/or post-void
based Practice Center for
the preparation of the
residual assessment may be performed and information from bladder diaries
evidence report and/or symptom questionnaires may be obtained. Clinical Principle
commissioned by the
Agency for Healthcare 3. Urodynamics, cystoscopy and diagnostic renal and bladder ultrasound should
Research and Quality not be used in the initial workup of the uncomplicated patient. Clinical Principle
(AHRQ).

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

4. OAB is not a disease; it is a symptom complex that generally is not a life-threatening condition. After assessment
has been performed to exclude conditions requiring treatment and counseling, no treatment is an acceptable
choice made by some patients and caregivers. Expert Opinion

5. Clinicians should provide education to patients regarding normal lower urinary tract function, what is known about
OAB, the benefits vs. risks/burdens of the available treatment alternatives and the fact that acceptable symptom
control may require trials of multiple therapeutic options before it is achieved. Clinical Principle

Treatment:

First-Line Treatments:

6. Clinicians should offer behavioral therapies (e.g., bladder training, bladder control strategies, pelvic floor muscle
training, fluid management) as first line therapy to all patients with OAB. Standard (Evidence Strength Grade B)

7. Behavioral therapies may be combined with pharmacologic management. Recommendation (Evidence Strength
Grade C)

Second-Line Treatments:

8. Clinicians should offer oral anti-muscarinics or oral β3-adrenoceptor agonists as second-line therapy. Standard
(Evidence Strength Grade B)

9. If an immediate release (IR) and an extended release (ER) formulation are available, then ER formulations should
preferentially be prescribed over IR formulations because of lower rates of dry mouth. Standard (Evidence
Strength Grade B)

10. Transdermal (TDS) oxybutynin (patch [now available to women ages 18 years and older without a prescription]*
or gel) may be offered. Recommendation (Evidence Strength Grade C)*Revised June 11, 2013

11. If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one anti-
muscarinic medication, then a dose modification or a different anti-muscarinic medication or a β3-adrenoceptor
agonist may be tried. Clinical Principle

12. Clinicians should not use anti-muscarinics in patients with narrow-angle glaucoma unless approved by the
treating ophthalmologist and should use anti-muscarinics with extreme caution in patients with impaired gastric
emptying or a history of urinary retention. Clinical Principle

13. Clinicians should manage constipation and dry mouth before abandoning effective anti-muscarinic therapy.
Management may include bowel management, fluid management, dose modification or alternative anti-
muscarinics. Clinical Principle

14. Clinicians must use caution in prescribing anti-muscarinics in patients who are using other medications with anti-
cholinergic properties. Expert Opinion

15. Clinicians should use caution in prescribing anti-muscarinics or β3-adrenoceptor agonists in the frail OAB patient.
Clinical Principle

16. Patients who are refractory to behavioral and pharmacologic therapy should be evaluated by an appropriate
specialist if they desire additional therapy. Expert Opinion

Third-line Treatments:

17. Clinicians may offer intradetrusor onabotulinumtoxinA (100U) as third-line treatment in the carefully-selected
and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments. The patient
must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

catheterization if necessary. Standard Option (Evidence Strength Grade B C)

18. Clinicians may offer peripheral tibial nerve stimulation (PTNS) as third line treatment in a carefully selected
patient population. Recommendation (Evidence Strength Grade C)

19. Clinicians may offer sacral neuromodulation (SNS) as third line treatment in a carefully selected patient
population characterized by severe refractory OAB symptoms or patients who are not candidates for second-line
therapy and are willing to undergo a surgical procedure. Recommendation (Evidence Strength – Grade C)

20. Practitioners and patients should persist with new treatments for an adequate trial in order to determine
whether the therapy is efficacious and tolerable. Combination therapeutic approaches should be assembled
methodically, with the addition of new therapies occurring only when the relative efficacy of the preceding
therapy is known. Therapies that do not demonstrate efficacy after an adequate trial should be ceased. Expert
Opinion

Additional Treatments:

21. Indwelling catheters (including transurethral, suprapubic, etc.) are not recommended as a management strategy
for OAB because of the adverse risk/benefit balance except as a last resort in selected patients. Expert Opinion

22. In rare cases, augmentation cystoplasty or urinary diversion for severe, refractory, complicated OAB patients
may be considered. Expert Opinion

Follow-Up:

23. The clinician should offer follow up with the patient to assess compliance, efficacy, side effects and possible
alternative treatments. Expert Opinion

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AUA/SUFU Guideline Overactive Bladder

Introduction

Introduction therapies, including sacral neuromodulation (SNS) and

peripheral tibial nerve stimulation (PTNS) (also known
Section 1: Purpose as posterior tibial nerve stimulation) and limited
information regarding the use of intravesical
This guideline’s purpose is to provide direction to
onabotulinumtoxinA to treat non-neurogenic OAB
clinicians and patients regarding how to recognize non-
patients, additional searches were performed to
neurogenic overactive bladder (OAB), conduct a valid
capture this literature and relevant data were added to
diagnostic process and approach treatment with the
the database. The AUA update literature review
goals of maximizing symptom control and patient
process, in which an additional systematic review is
quality of life while minimizing adverse events and
conducted periodically to maintain guideline currency
patient burden. The strategies and approaches
with newly-published relevant literature, was conducted
recommended in this document were derived from
in February 2014. This review identified an additional
evidence-based and consensus-based processes. There
72 articles relevant to treatment. These articles were
is a continually expanding literature on OAB; the Panel
added to the database, and AUA’s qualitative and
notes that this document constitutes a clinical strategy
quantitative analyses were updated as appropriate.
and is not intended to be interpreted rigidly. The most
effective approach for a particular patient is best Data from studies published after the literature search
determined by the individual clinician and patient. As cut-off will be incorporated into the next version of this
the science relevant to OAB evolves and improves, the guideline. Preclinical studies (e.g., animal models),
strategies presented here will require amendment to pediatric studies, commentary and editorials were
remain consistent with the highest standards of clinical eliminated. Review article references were checked to
care. This document was created to serve as a guide ensure inclusion of all possibly relevant studies.
for all types of providers who evaluate and treat OAB Multiple reports on the same patient group were
patients, including those in general practice as well as carefully examined to ensure inclusion of only
those who specialize in various branches of medicine. nonredundant information.

Section 2: Methodology OAB Diagnosis. The review revealed insufficient

publications to address OAB diagnosis from an evidence
The primary source of evidence for the first version of
basis; the diagnosis portions of the algorithm (see
this guideline was the systematic review and data
Figure 1), therefore, are provided as Clinical Principles
extraction conducted as part of the Agency for
or as Expert Opinion with consensus achieved using a
Healthcare Research and Quality (AHRQ) Evidence
modified Delphi technique if differences of opinion
Report/Technology Assessment Number 187 titled
emerged.2 A Clinical Principle is a statement about a
Treatment of Overactive Bladder in Women (2009).1
component of clinical care that is widely agreed upon
That report, prepared by the Vanderbilt University
by urologists or other expert clinicians for which there
Evidence-Based Practice Center (EPC), searched
may or may not be evidence in the medical literature.
PubMed, MEDLINE, EMBASE and CINAHL for English-
Expert Opinion refers to a statement, achieved by
language studies published from January 1966 to
consensus of the Panel, that is based on members'
October 2008 relevant to OAB and excluded non-
clinical training, experience, knowledge and judgment
relevant studies, studies with fewer than 50
for which there is no evidence.
participants and studies with fewer than 75% women.
AUA conducted an additional literature search to OAB Treatment. With regard to treatment, a total of
capture articles published between October 2008 and 151 articles from the original search processes met the
December 2011. In addition, because the Panel wished inclusion criteria; an additional 72 relevant articles
to consider data for male as well as female patients, were retrieved as part of the update literature review
studies excluded by the AHRQ report because there process and also have been incorporated. The Panel
were fewer than 75% women participants were judged that these were a sufficient evidence base from
extracted and added to the database. Studies that which to construct the majority of the treatment
focused primarily on nocturia were also added to the portion of the algorithm. Data on study type (e.g.,
database. Given that the AHRQ report included limited randomized controlled trial, controlled clinical trial,
information regarding use of neuromodulation observational study), treatment parameters (e.g.,

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AUA/SUFU Guideline Overactive Bladder

Introduction

dose, administration protocols, follow-up durations), The categorization of evidence strength (ES) is
patient characteristics (i.e., age, presence of specific conceptually distinct from the quality of individual
symptoms such as urgency, urgency incontinence and/ studies. Evidence strength refers to the body of
or frequency, detrusor overactivity documented by evidence available for a particular question and includes
urodynamics), adverse events, and primary outcomes consideration of study design, individual study quality,
(as defined by study authors) were extracted. The consistency of findings across studies, adequacy of
primary outcomes for most studies were reductions in sample sizes and generalizability of samples, settings
frequency, urgency incontinence, incontinence and and treatments for the purposes of the guideline. AUA
urgency. categorizes evidence strength as Grade A (well-
conducted RCTs or exceptionally strong observational
The quality of individual studies was assessed by the studies), Grade B (RCTs with some weaknesses of
EPC using accepted criteria to determine the quality of procedure or generalizability or generally strong
internal and external validity. The criteria and rating observational studies) or Grade C (observational
scheme are described in detail in the published report studies that are inconsistent, have small sample sizes
The same system was used to assess the quality of or have other problems that potentially confound
additional included studies. interpretation of data).

AUA Nomenclature: Linking Statement Type to

Table 1: AUA Nomenclature Evidence Strength. The AUA nomenclature system
Linking Statement Type to Level of Certainty and
explicitly links statement type to body of evidence
Evidence Strength [Updated Version]
strength and the Panel’s judgment regarding the
Standard: Directive statement that an action should
(benefits outweigh risks/burdens) or should not (risks/ balance between benefits and risks/burdens. 3
burdens outweigh benefits) be taken based on Grade A Standards are directive statements that an action
(high quality; high certainty) or B (moderate quality; should (benefits outweigh risks/burdens) or should not
moderate certainty) evidence (risks/burdens outweigh benefits) be undertaken based
Recommendation: Directive statement that an action on Grade A (high level of certainty) or Grade B
should (benefits outweigh risks/burdens) or should not ( m o d e r at e le ve l of c e r t a i nt y) e vi de nc e .
(risks/burdens outweigh benefits) be taken based on Recommendations are directive statements that an
Grade C (low quality; low certainty) evidence action should (benefits outweigh risks/burdens) or
Option: Non-directive statement that leaves the deci- should not (risks/burdens outweigh benefits) be
sion regarding an action up to the individual clinician undertaken based on Grade C (low level of certainty)
and patient because the balance between benefits and evidence. Options are non-directive statements that
risks/burdens appears equal or appears uncertain based
leave the decision to take an action up to the individual
on Grade A (high quality; high certainty), B (moderate
clinician and patient because the balance between
quality; moderate certainty), or C (low quality; low
certainty) evidence benefits and risks/burdens appears relatively equal or
Clinical Principle: a statement about a component of unclear; Options may be supported by Grade A (high
clinical care that is widely agreed upon by urologists certainty), B (moderate certainty) or C (low certainty)
or other clinicians for which there may or may not be evidence. Options generally reflect the Panel’s
evidence in the medical literature judgment that a particular decision is best made by the
Expert Opinion: a statement, achieved by consensus clinician who knows the patient with full consideration
of the Panel, that is based on members' clinical train- of the patient’s prior treatment history, current quality
ing, experience, knowledge, and judgment for which of life, preferences and values.
there is no evidence
Limitations of the Literature. The Panel proceeded
with full awareness of the limitations of the OAB
literature. For example, despite the relatively large
number of randomized controlled trials (RCTs) with
placebo control groups and randomized designs with
active controls that assessed pharmacologic OAB
treatments, the overwhelming majority of trials
followed patients for only 12 weeks. Additional

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AUA/SUFU Guideline Overactive Bladder

Introduction

limitations included the use of different inclusion criteria Section 3: Background

across studies assessing the same treatment, poorly-
defined patient groups or use of patient groups with Definition. Overactive bladder (OAB) is a clinical
limited generalizability to the typical clinical setting in diagnosis characterized by the presence of bothersome
which OAB patients are seen, lack of consistency in urinary symptoms. Most studies of OAB, including this
outcome measures and limited outcome measure and guideline, exclude individuals with symptoms related to
adverse event reporting. With regard to measures, neurologic conditions. The International Continence
although most studies reported urinary frequency and Society (ICS) defines OAB as the presence of “urinary
urinary incontinence, many studies did not report other urgency, usually accompanied by frequency and
key measures such as urgency, and only a handful nocturia, with or without urgency urinary incontinence,
reported nocturia data. With regard to adverse events, in the absence of UTI or other obvious pathology.”4
most pharmacologic studies reported rates of dry Therefore, OAB symptoms consist of four components:
mouth and constipation, but few reported on other urgency, frequency, nocturia and urgency incontinence.
clinically-relevant issues such as cardiac or cognitive OAB studies have used varying combinations of these
adverse events. The original completed evidence symptoms to identify patients for study inclusion and to
report and the updated literature review evidence define treatment response. These methodologic
report may be requested from AUA. differences across studies make it a challenge to
interpret the OAB literature related to epidemiology and
The Overactive Bladder Panel was created in 2009 by treatment.
the American Urological Association Education and
Research, Inc. (AUA). The Practice Guidelines Urgency is defined by the ICS as the “complaint of a
Committee (PGC) of the AUA selected the Panel Chair sudden, compelling desire to pass urine which is
and Vice Chair who in turn appointed the additional difficult to defer.”4 Urgency is considered the hallmark
panel members with specific expertise in this area. The symptom of OAB, but it has proven difficult to precisely
AUA conducted a thorough peer review process of the define or to characterize for research or clinical
original document. The draft guidelines document was purposes. Therefore, many studies of OAB treatments
distributed to 78 peer reviewers, of whom 31 provided have relied upon other measures (e.g., number of
comments. The panel reviewed and discussed all voids, number of incontinence episodes) to measure
submitted comments and revised the draft as needed. treatment response.
Once finalized, the guideline was submitted for approval
Urinary frequency can be reliably measured with a
to the PGC. Then it was submitted to the AUA Board of
voiding diary. Traditionally, up to seven micturition
Directors (BOD) for final approval. Funding of the
episodes during waking hours has been considered
panel was provided by the AUA and the Society of
normal,5 but this number is highly variable based upon
Urodynamics, Female Pelvic Medicine & Urogenital
hours of sleep, fluid intake, comorbid medical
Reconstruction (SUFU), although panel members
conditions and other factors.
received no remuneration for their work. AUA’s
amendment process provides for the amendment of
Nocturia is the complaint of interruption of sleep one or
existing evidence-based guideline statements and/or
more times because of the need to void.4 In one study,
the creation of new evidence-based guideline
three or more episodes of nocturia constitutes
statements in response to the publication of a sufficient
moderate or major bother.6 Like daytime frequency,
volume of new evidence. The process also provides for
nocturia is a multifactorial symptom which is often due
the amendment or addition of Clinical Principle and
to factors unrelated to OAB (e.g., excessive nighttime
Expert Opinion statements based on consensus among
urine production, sleep apnea).
panel members that elements of current practice have
shifted such that a new or revised Clinical Principle or Urgency urinary incontinence is defined as the
Expert Opinion statement is needed. Evidence-based involuntary leakage of urine, associated with a sudden
guideline amendments require the agreement of a compelling desire to void. Incontinence episodes can
methodologist and panel members that new evidence is be measured reliably with a diary, and the quantity of
sufficient to change or add evidence-based statements. urine leakage can be measured with pad tests.
All guideline amendments require approval of the AUA However, in patients with mixed urinary incontinence
Practice Guidelines Committee (PGC) and BOD. (both stress and urgency incontinence), it can be

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AUA/SUFU Guideline Overactive Bladder

Introduction

difficult to distinguish between incontinence subtypes. psychosocial functioning and quality of life also has
Therefore, it is common for OAB treatment trials to been well-documented.19-22 Carrying out the activities
utilize total incontinence episodes as an outcome of daily life and engaging in social and occupational
measure. activities can be profoundly affected by lack of bladder
control and incontinence. Urinary incontinence in
Epidemiology. In population-based studies, OAB particular may have severe psychological and social
prevalence rates range from 7% to 27% in men, and consequences, resulting in restricted activities and
9% to 43% in women.7-14 No clear differences exist unwillingness to be exposed to environments where
between studies conducted in North America vs. other access to a bathroom may be difficult. Patients also
populations. Some studies report higher prevalence report negative impact on sexual function and marital
rates in women than men,7-10 while others found similar satisfaction23 and OAB symptoms have been linked to
rates across genders.11-14 However, urgency urinary depressive illness.24, 25 This negative impact also is
incontinence is consistently more common in women evident among older adults (e.g., ≥ 65 years), resulting
than in men. OAB symptom prevalence and severity in significant impairments in QoL, including high rates
tend to increase with age.11-12, 15 A proportion of OAB of anxiety and depression, with the majority of patients
cases (37-39%) remit during a given year, but the reporting they have not sought treatment.26
majority of patients have symptoms for years.15, 16 To
date, no population-based studies have directly Successful treatment of OAB symptoms with behavioral
examined epidemiologic differences across racial/ethnic approaches, medications, neuromodulation therapies,
groups. and onabotulinumtoxinA, balanced against adverse
events, costs and ultimately patient compliance, all
Patient-Reported Outcomes (PROs) and OAB. have been reported to improve patient quality of life
Since OAB is a symptom-based diagnosis, the quality of (see Discussion sections under each treatment type).
life (QOL) impact of the symptoms is a critical aspect of
the condition. The degree of bother caused by OAB Section 4: Patient Presentation
symptoms directly affects OAB care-seeking, treatment
intensity and satisfaction with treatment. Therefore, Symptoms. When symptoms of urinary frequency
assessment of patient-reported outcomes (PROs) can (both daytime and night) and urgency, with or without
be a critical component of OAB management. urgency incontinence, are self-reported as bothersome
Numerous questionnaire instruments have been the patient may be diagnosed with overactive bladder
developed to assess symptoms, degree of bother and (OAB).27 Additionally, a caregiver or partner may
health-related QOL in patients with OAB and urinary perceive these symptoms as bothersome and lead the
incontinence.17 This lack of standardization has often patient to seek care. It is common for patients to have
limited the comparability and generalizability of PROs suffered with their symptoms for an extended time
across research studies. To address this, the before seeking medical advice.
International Consultation on Incontinence has
Differentiation. OAB symptoms (frequency, urgency
developed a series of standardized modular
and urgency incontinence) may occur only at night,
questionnaires for pelvic conditions, including OAB.18
causing a single symptom of nocturia. The differential
The Panel encourages the development of such
of nocturia includes nocturnal polyuria (the production
standardized PRO tools which can be used in OAB
of greater than 20 to 33% of total 24 hour urine output
research and clinical practice.
during the period of sleep, which is age-dependent with
Impact on Psychosocial Functioning and Quality 20% for younger individuals and 33% for elderly
of Life (QoL). The Panel fully recognizes that OAB individuals),28 low nocturnal bladder capacity or both.
constitutes a significant burden for patients. These In nocturnal polyuria, nocturnal voids are frequently
burdens include the time and effort required to manage normal or large volume as opposed to the small volume
symptoms during the course of daily life as well as the voids commonly observed in nocturia associated with
resources required to obtain treatments that may be OAB. Sleep disturbances, vascular and/or cardiac
costly and may present logistical challenges (e.g., disease and other medical conditions are often
therapies that require frequent visits to a physician’s associated with nocturnal polyuria. As such, it is often
office). The negative impact of OAB symptoms on age-dependent, increasing in prevalence with aging and

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

with poorer general health. process are a careful history, physical exam and
urinalysis. Clinical Principle
OAB also must be distinguished from other conditions
such as polydipsia. In OAB, urinary frequency is Discussion. History. The clinician should carefully
associated with many small volume voids. Frequency elicit the patient’s bladder symptoms to document
that is the result of polydipsia and resulting polyuria duration of symptoms and baseline symptom levels, to
may mimic OAB; the two can only be distinguished with ensure that symptoms are not the consequence of
the use of frequency-volume charts. In polydipsia, some other condition and to determine whether the
urinary frequency occurs with normal or large volume patient constitutes a complex OAB presentation that
voids and the intake is volume matched. In this case, may require referral. Questions should assess bladder
the frequency is appropriate because of the intake storage symptoms associated with OAB (e.g., urgency,
volume and the patient does not have OAB. Frequency urgency incontinence, frequency, nocturia), other
due to polydipsia is physiologically self-induced OAB bladder storage problems (e.g., stress incontinence
and should be managed with education, with episodes) and bladder emptying (e.g., hesitancy,
consideration of fluid management. Similarly, diabetes straining to void, prior history of urinary retention,
insipidus (DI) also is associated with frequent, large force of stream, intermittency of stream). The
volume voids and should be distinguished from OAB. symptom of urgency as defined by the ICS is the
“complaint of sudden compelling desire to pass urine
The clinical presentation of interstitial cystitis/ bladder which is difficult to defer.”27 The interpretations of
pain syndrome shares the symptoms of urinary “sudden” and “compelling” are highly subjective and
frequency and urgency, with or without urgency difficult to quantitate. Nevertheless, the clinician can
incontinence; however, bladder and/or pelvic pain, simply ask if the patient has a problem getting to the
including dyspareunia, is a crucial component of its bathroom in time, assuming the patient has normal
presentation in contradistinction to OAB. Other mobility.
conditions also can contribute to OAB symptoms and
should be assessed. For example, in the menopausal Bladder function is related to amount and type of fluid
female patient, atrophic vaginitis can be a contributing intake. Excessive fluid intake can produce voiding
factor to incontinence symptoms. There is some patterns that mimic OAB symptoms. For this reason,
evidence for symptom improvement with the use of an inquiry into fluid intake habits should be performed,
vaginal (but not systemic) estrogen.29 including asking patients how much fluid and of what
type (e.g., with or without caffeine) they drink each
Section 5: Diagnosis day, how many times they void each day and how
many times they void at night. Patients who do not
The Diagnostic Approach. Insufficient literature was
appear able to provide accurate intake and voiding
identified to constitute an evidence base for diagnosis
information should fill out a fluid diary. Urinary
of OAB in clinical practice. For this reason, the section
frequency varies across individuals. In community-
titled Diagnosis is based on Clinical Principles or Expert
dwelling healthy adults, normal frequency consists of
Opinion with consensus achieved using a modified
voiding every three to four hours with a median of
Delphi technique when differences of opinion emerged.
approximately six voids a day.30, 31 Current medication
This section is intended to provide clinicians and
use also should be reviewed to ensure that voiding
patients with a framework for determining whether a
symptoms are not a consequence of a prescribed
diagnosis of OAB is appropriate; it is not intended to
medication, particularly diuretics.
replace the judgment and experience of the individual
clinician faced with a particular patient. The degree of bother from bladder symptoms also
should be assessed. If a patient is not significantly
Guideline Statement 1.
bothered by his/her bladder symptoms, then there
would be less compelling reason to treat the symptoms.
The clinician should engage in a diagnostic
Degree of bother can affect different domains of daily
process to document symptoms and signs that
activities related to work and leisure. Patients may
characterize OAB and exclude other disorders
avoid certain activities (e.g., travel, situations that do
that could be the cause of the patient’s
not allow easy access to a toilet) because of their
symptoms; the minimum requirements for this

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

bladder symptoms. and has therapeutic implications regarding goals and

options. The Mini-Mental State Examination (MMSE)32
Co-morbid conditions should be completely elicited as is a standardized, quick and useful assessment of
these conditions may directly impact bladder function. cognitive function. An MMSE should be conducted on
Patients with co-morbid conditions and OAB symptoms all patients who may be at risk for cognitive impairment
would be considered complicated OAB patients. These to determine whether symptoms are aggravated by
co-morbid conditions include neurologic diseases (i.e., cognitive problems, to ensure that they will be able to
stroke, multiple sclerosis, spinal cord injury), mobility follow directions for behavioral therapy and/or to
deficits, medically complicated/uncontrolled diabetes, determine the degree of risk for cognitive decline with
fecal motility disorders (fecal incontinence/ anti-muscarinic therapy. In the Panel’s experience, the
constipation), chronic pelvic pain, history of recurrent ability of the patient to dress independently is
urinary tract infections (UTIs), gross hematuria, prior informative of sufficient motor skills related to toileting
pelvic/vaginal surgeries (incontinence/prolapse habits.
surgeries), pelvic cancer (bladder, colon, cervix, uterus,
prostate) and pelvic radiation. The female patient with Urinalysis. A urinalysis to rule out UTI and hematuria
significant prolapse (i.e., prolapse beyond the introitus) should be performed. A urine culture is not necessary
also may be considered a complicated OAB patient. unless indication of infection (i.e., nitrites/leukocyte
Patients with urgency incontinence, particularly younger esterase on dipstick, pyuria/bacteriuria on microscopic
patients, or a patient with extremely severe symptoms exam) is found and may be done at the discretion of
could represent a complicated OAB patient with an the clinician. If evidence of infection is detected, then a
occult neurologic condition. A patient who has failed culture should be performed, the infection treated
multiple anti-muscarinics to control OAB symptoms appropriately and the patient should be queried
could also be considered a complicated OAB patient. If regarding symptoms once the infection has cleared. If
the history elicits any of these co-morbid conditions evidence of hematuria not associated with infection is
and/or special situations, then the clinician should found, then the patient should be referred for urologic
consider referring these patients to a specialist for evaluation.
further evaluation and treatment.
Guideline Statement 2.
Physical Examination. A careful, directed physical exam
should be performed. An abdominal exam should be In some patients, additional procedures and
performed to assess for scars, masses, hernias and measures may be necessary to validate an OAB
areas of tenderness as well as for suprapubic distension diagnosis, exclude other disorders and fully
that may indicate urinary retention. Examination of inform the treatment plan. At the clinician’s
lower extremities for edema should be done to give the discretion, a urine culture and/or post-void
clinician an assessment of the potential for fluid shifts residual assessment may be performed and
during periods of postural changes. A rectal/ information from bladder diaries and/or symptom
genitourinary exam to rule out pelvic floor disorders questionnaires may be obtained. Clinical
(e.g., pelvic floor muscle spasticity, pain, pelvic organ Principle
prolapse) in females and prostatic pathology in males
Discussion. Urine culture. Urinalysis is unreliable for
should be performed. In menopausal females, atrophic
identification of bacterial counts below 100,000cfu/ml.
vaginitis should be assessed as a possible contributing
In some patients with irritative voiding symptoms but
factor to incontinence symptoms. The examiner should
without overt signs of infection, a urine culture may be
assess for perineal skin for rash or breakdown. The
appropriate to completely exclude the presence of
examiner also should assess perineal sensation, rectal
clinically significant bacteriuria.
sphincter tone and ability to contract the anal sphincter
in order to evaluate pelvic floor tone and potential
Post-void residual (PVR). Measurement of the post-
ability to perform pelvic floor exercises (e.g., the ability
void residual (PVR) is not necessary for patients who
to contract the levator ani muscles) as well as to rule
are receiving first-line behavioral interventions (see
out impaction and constipation.
Guideline Statement 6 below) or for uncomplicated
patients (i.e., patients without a history of or risk
Cognitive impairment is related to symptom severity
factors for urinary retention) receiving anti-muscarinic

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medications. Because anti-muscarinic medications can between polyuria (characterized by normal or large
induce urinary retention,33 particularly in complicated volume voids) from OAB (characterized by frequent
patients with retention risk factors, PVR should be small voids). It is more burdensome, however, and is
assessed in patients with obstructive symptoms, history usually completed for only 24 to 48 hours.
of incontinence or prostatic surgery, neurologic
diagnoses and in other patients at clinician discretion The bladder diary is a useful tool for both the clinician
when PVR assessment is deemed necessary to optimize and the patient. In the evaluation phase, it provides
care and minimize potential risks. It should be noted, information that can help the clinician plan appropriate
however, that the occurrence of symptomatic urinary components of intervention, particularly behavioral
retention or asymptomatic elevations of postvoid intervention. Recording the times that the patient
residuals after the addition of anti-muscarinic agents voids provides a foundation for determining voiding
occurs in a small proportion of patients; previously intervals in bladder training programs. During the
undiagnosed poor detrusor function may be unmasked course of treatment, it can be used to monitor
in those individuals. symptoms to track the efficacy of various treatment
components and guide the intervention. For the
PVR should be measured with an ultrasound bladder patient, the self-monitoring effect of completing the
scanner immediately after the patient voids. If an diary enhances awareness of voiding habits and helps
ultrasound scanner is not available, then urethral them recognize activities that can trigger incontinence.
catheterization may be used to assess PVR. For any Twenty-four hour pad weights also can provide useful
patient on anti-muscarinic therapy, the clinician should information regarding the severity of incontinence
be prepared to monitor PVR during the course of symptoms.
treatment should obstructive voiding symptoms appear.
As there is considerable overlap between storage and Symptom questionnaires. Validated symptom
emptying voiding symptoms, baseline PVRs should be questionnaires have been utilized in OAB clinical trials
performed for men with symptoms prior to initiation of to quantitate bladder symptom and bother changes
anti-muscarinic therapy. Anti-muscarinics should be with OAB therapies. Among these questionnaires are
used with caution in patients with PVR >250-300 mL.34 the Urogenital Distress Inventory (UDI), the UDI-6
Most randomized trials that evaluated anti-muscarinics Short Form, the Incontinence Impact Questionnaire (II-
for OAB treatment used a PVR of 150-200 mL as an Q) and the Overactive Bladder Questionnaire (OAB-q).35
-37
exclusion criterion; the overwhelming majority of The rationale for utilization of these validated
participants in these trials were women. questionnaires is to quantitate and follow the patients’
responses to OAB treatment as well as to obtain
Bladder diaries. Diaries that document intake and baseline and post-treatment levels of bother.
voiding behavior may be useful in some patients,
particularly the patient who cannot describe or who is Guideline Statement 3.
not familiar with intake and voiding patterns. Diaries
Urodynamics, cystoscopy and diagnostic renal
also are useful to document baseline symptom levels so
and bladder ultrasound should not be used in the
that treatment efficacy may be assessed.
initial workup of the uncomplicated patient.
In particular, self-monitoring with a bladder diary for Clinical Principle
three to seven days is a useful first step in initiating
Discussion. Urodynamics, cystoscopy and diagnostic
behavioral treatments for OAB. At a minimum, the
renal and bladder ultrasound are not recommended in
patient documents the time of each void and
the initial diagnostic workup of the uncomplicated OAB
incontinence episode and the circumstances or reasons
patient. For complicated patients or refractory patients
for the incontinence episode. Rating the degree of
who have failed multiple OAB treatments, the choice of
urgency associated with each void and incontinence
additional diagnostic tests depends on patient history
episode also can be useful. Adding measures of voided
and presentation and clinician judgment. In some
volumes can provide a practical estimate of the
cases, additional information may make clear that the
patient’s functional bladder capacity in daily life and
patient has neurogenic OAB rather than non-neurogenic
estimate the amount of overall fluid intake. Recording
OAB and requires a different treatment plan. Patients
voided volumes also can be useful to differentiate
with hematuria should be referred for a urologic work

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Guideline Statements

up. In the low-risk uncomplicated patient without it is in the patient’s best interests. In these patients,
microscopic hematuria, urine cytology is infrequently behavioral strategies that include prompted voiding and
associated with atypia requiring further investigation, fluid management may be helpful. Pharmacologic
engendering costs and possibly resulting in morbidity. treatments and invasive treatments, however, are
Urine cytology is not recommended in the routine generally not appropriate for these individuals. The
evaluation of patients with uncomplicated OAB without Panel also recognizes that untreated incontinence can
hematuria who respond to therapy. result in falls when a patient with compromised mobility
attempts to move quickly to a toileting facility. The
Guideline Statement 4. treating physician, the patient and the caregiver must
weigh these risks when making the decision whether
OAB is not a disease; it is a symptom complex
and how to treat OAB.
that generally is not a life threatening condition.
After assessment has been performed to exclude Guideline Statement 5.
conditions requiring treatment and counseling, no
treatment is an acceptable choice made by some Clinicians should provide education to patients
patients and caregivers. Expert Opinion regarding normal lower urinary tract function,
what is known about OAB, the benefits vs. risks/
Discussion. Initiating treatment for OAB generally burdens of the available treatment alternatives
presumes that the patient can perceive an and the fact that acceptable symptom control may
improvement in his or her quality of life. In patients require trials of multiple therapeutic options
who cannot perceive symptom improvements, before it is achieved. Clinical Principle.
treatment may not be appropriate, may be potentially
unsafe or may be futile (e.g., in the very elderly or Discussion. Prior to initiating treatment, the clinician
demented patient) except in patients for whom OAB should provide patient education regarding normal and
symptoms present a significant health risk (e.g., risk abnormal bladder function, including voiding frequency
for skin breakdown). It is important for clinicians who and toileting behavior. Explaining what is normal can
treat this problem to recognize this issue and to set help the patient understand how their condition
feasible therapeutic goals with the patient and/or diverges from normal and gives them a comparator (or
caregiver. The presence of an overactive bladder goal) for judging their own progress in treatment.
frequently accompanies other disorders such as Education also empowers the patient to engage and
deficiencies in cognition (i.e., dementia) and/or poor participate in their treatment, which is essential when
mobility, which can complicate treatment. To treat using interventions that rely on behavior change.
incontinence, optimally the patient must have a desire Patients must understand that voiding is a behavior
to be continent or have a desire for symptom that can be managed and that successful OAB
improvement. In patients with cognitive deficits, this treatment requires a willing participant who is informed
desire may not be present and family and/or caregivers and engaged in the treatment process.
may have difficulty understanding that simply giving a
medication will not correct the problem. The other Patients should be informed that OAB is a symptom
common situation associated with OAB is severely complex with a variable and chronic course that needs
reduced mobility. Causes can range from dementia, to be managed over time, that it primarily affects
severe arthritis, severe obesity, hemiparesis/plegia, quality of life, that there is no single ideal treatment
and lower extremity amputations. In these situations, and that available treatments vary in the effort required
despite receiving an urge to urinate, the patient from the patient as well as in invasiveness, risk of
physically cannot get from their current position without adverse events and reversibility. An effective
assistance to a toileting facility. This cannot be treatment plan depends on patients having realistic
corrected pharmacologically and should be recognized goals for treatment and a clear understanding of the
by the treating physician. risks and burdens of particular treatments. In this
context, it is important to understand the patient's
In certain patients for whom hygiene and skin expectations of treatment, not only in terms of its
breakdown are major concerns, treatment may be outcome, but regarding what is required of them as
considered regardless of the patient’s perceptions when well. Expectations are important because they affect

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motivation and adherence, and they can influence the conceptualized risks/burdens in terms of the
patient's interpretation of treatment effects and invasiveness of the treatment, the duration and
satisfaction with outcomes. severity of potential adverse events and the
reversibility of potential adverse events. Treatment
Most OAB treatments can improve patient symptoms alternatives were then divided into first-, second-, third
but not eliminate them. The available OAB treatments, -, fourth- and fifth-line groups. This hierarchy was
with the exception of behavioral therapies, present derived by balancing the potential benefits to the
risks for adverse events, some of which are serious. patient with the invasiveness of the treatment, the
When initiating behavioral interventions, it is crucial duration and severity of potential adverse events and
that the patient understands that treatment progress the reversibility of potential adverse events. Note that
and outcomes will depend on their active participation the hierarchy was not established based on the number
and persistence over time. It is also useful for them to of available studies or on the evidence strength for a
understand several other aspects of behavioral change: particular treatment. For example, first-line treatment
progress is usually gradual, change can be irregular with behavioral therapy presents essentially no risks to
with good days and bad days and long-term change in patients and should be offered to all patients. Second-
symptoms depends on their long-term change in line treatment with oral or transdermal anti-muscarinics
behavior. or β3-adrenoceptor agonists is not invasive and
presents the risk of side effects that primarily
Patients may decide that the symptomatic improvement
compromise quality of life. Any adverse events are
achieved with a particular therapy (e.g., from 5
readily reversible with cessation of the medication.
incontinence episodes per day to 3 incontinence
Third-line treatment with intradetrusor
episodes per day) is not worthwhile given the adverse
onabotulinumtoxinA is invasive and presents risks for
events associated with that treatment (e.g., dry mouth
infection as well as increased post-void residuals and
and constipation associated with anti-muscarinic
the potential need for self-catheterization, which is not
therapy) and choose to discontinue therapy despite
quickly reversible. Various neuromodulation therapies
symptomatic improvement. Choosing to forego
(PTNS, SNS) require active participation by a motivated
treatment is a valid decision. It is the opinion of the
patient. Sacral neuromodulation is invasive and
Panel that patients seeking treatment initially and at
presents the risk of rare adverse events that may not
any point in the treatment algorithm should be told that
be quickly reversible, such as infection. Additional
they may opt for no treatment with minimal adverse
treatments, such as various kinds of surgery, present
effects on their health and no impact on the success of
the risks of major surgery and are irreversible.
later management should they choose to pursue
treatment in the future. Given that idiopathic OAB is a chronic syndrome
without an ideal treatment and no treatment will cure
Section 6: Treatment
the condition in most patients, clinicians should be
prepared to manage the transition between treatment
Issues to Consider. It is important to recognize that
levels appropriately. Treatment failure occurs when the
OAB is a symptom complex that may compromise
patient does not have the desired change in their
quality of life (QoL) but generally does not affect
symptoms or is unable to tolerate the treatment due to
survival. Given this context, in pursuing a treatment
adverse events; lack of efficacy and the presence of
plan the clinician should carefully weigh the potential
intolerable adverse events reduce compliance. The
benefit to the patient of a particular treatment against
interaction between efficacy, tolerability and compliance
that treatment’s risk for adverse events, the severity of
is termed clinical effectiveness.38 To optimize
adverse events and the reversibility of adverse events.
effectiveness, it is critical for patients to have realistic
The guideline statements in this section are intended to
expectations regarding likely treatment effects and
provide a framework to assist the clinician in counseling
adverse events.
patients and in developing an individualized treatment
plan that optimizes quality of life.
Bladder diaries that document voiding behavior can be
useful to monitor efficacy and guide treatment. In
In developing the treatment portion of the algorithm,
particular, diaries and validated questionnaires can be
the balance between benefits and risks/burdens (i.e.,
helpful to quantify baseline symptom levels and
adverse events) was considered. The Panel

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treatment effects so that both the patient and the improve OAB symptoms by changing patient behavior
clinician can assess whether a particular treatment or changing the patient's environment. Most effective
approach is alleviating symptoms and whether the behavioral treatment programs include multiple
balance between symptom control and adverse events components and are individualized to the unique needs
is appropriate for a given patient. of the patient and his/her unique living situation. There
are two fundamental approaches to behavioral
This clinical framework does not require that every treatment for OAB. One approach focuses on modifying
patient go through each line of treatment in order. bladder function by changing voiding habits, such as
There are many factors to consider when identifying the with bladder training and delayed voiding. The other
best treatment for a particular patient, including approach, behavioral training, focuses on the bladder
information regarding allergies, sensitivity to various outlet and includes pelvic floor muscle training to
adverse drug events, patient ability and motivation to improve strength and control and techniques for urge
comply and availability of and access to specific suppression. Specific components of behavioral
treatments. Behavioral therapies were selected as first- treatment can include self-monitoring (bladder diary),
line therapies because they present essentially no risks scheduled voiding, delayed voiding, double voiding,
to the patient. However, behavioral therapies require pelvic floor muscle training and exercise (including
an investment of time and effort by the patient to pelvic floor relaxation), active use of pelvic floor
achieve maximum benefits and may require sustained muscles for urethral occlusion and urge suppression
and regular contact with the clinician to maintain (urge strategies), urge control techniques (distraction,
regimen adherence and consequent efficacy.39 In self-assertions), normal voiding techniques,
patients who are unwilling or unable to comply with biofeedback, electrical stimulation, fluid management,
behavioral therapy regimens and instructions, it is caffeine reduction, dietary changes (avoiding bladder
appropriate to move to second-line pharmacologic irritants), weight loss and other life style changes. In
therapies. Failure and/or the experience of adverse addition, behavioral therapies have the advantage that
events with one medication should usually be they can be combined with all other therapeutic
addressed by trying at least one other medication techniques. Behavioral therapies are most often
before third-line therapies are considered (see implemented by advance practice nurses (e.g.,
Guideline Statement 11 below). In select patients who continence nurses) or physical therapists with training
are unable or unwilling to comply with pharmacologic in pelvic floor therapy.
management, third-line therapies of neuromodulation
(PTNS, SNS) and intradetrusor onabotulinumtoxinA Guideline Statement 6.
may be considered. Patients who are felt to be
reasonable candidates for third-line therapies who have Clinicians should offer behavioral therapies (e.g.,
been treated by nonspecialists will require referral to a bladder training, bladder control strategies, pelvic
specialist. In some cases the specialist may opt to floor muscle training, fluid management) as first
obtain further information with voiding diaries or line therapy to all patients with OAB. Standard
symptom questionnaires, or may do further testing
Discussion. (Evidence strength – Grade B;
such as urodynamics to rule out other bladder
Benefits outweigh risks/burdens). Behavioral
pathologies or urethral dysfunction. The use of
treatments are designated as first-line treatments
indwelling catheters as a management strategy is not
because they are as effective in reducing symptom
recommended except as a last resort in selected
levels as are anti-muscarinic medications, and they
patients. Surgical intervention should be reserved for
consist of many components that can be tailored to
the rare non-neurogenic patient who has failed all other
address the individual patient’s needs and capacities.
therapeutic options and whose symptoms are
In addition, they are relatively non-invasive and, in
intolerable.
contrast to medications, are associated with virtually no
adverse events. They do require the active
participation of the patient and/or of the patient’s
First-Line Treatments: Behavioral Therapies caregiver, however, as well as time and effort from the
clinician. Behavioral therapies should be offered to all
Behavioral treatments are a group of therapies that OAB patients, including OAB patients who require a

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Guideline Statements

caregiver; caregivers can be instructed in behavioral important in subjective outcomes. However, in a

techniques in order to optimize patient symptom comparison of pelvic floor muscle training with and
control (i.e., prompted voiding, timed voiding). without biofeedback, incontinence, pelvic muscle
strength and QoL improved more in the group that
Most of the literature on overactive bladder focuses on received feedback.49 In a study that compared PFMT to
the treatment of urinary incontinence, and most studies bladder training or PFMT in combination with bladder
have been performed with women. Although most training, patients in the combined group initially had
patients do not experience complete symptom relief greater incontinence reductions and QoL
with behavioral intervention, the literature indicates improvements; however, at 3 month follow-up all three
that most patients experience significant reductions in groups had similar improvement levels.50
symptoms and improvements in quality of life. The
literature provides clear support for the effectiveness of The literature review of comparative effectiveness
bladder training (incremental voiding schedules done randomized trials indicated that various types of
with distraction and self-assertions)41,42 and behavioral behavioral treatment were generally either equivalent
training (pelvic floor muscle training with urge to44, 51, 52 or superior to42, 45, 53 medications in terms of
suppression techniques).53 Typical mean improvements reducing incontinence episodes, improving voiding
range from 50% to 80% reduction in the frequency of parameters such as frequency43, 54, 55 and nocturia56 and
incontinence. Reductions in voiding frequency have improving QoL. Most studies evaluated oxybutynin
also been documented in men43 and women.41, 44, 45 (both the IR and the ER formulations).43, 44, 51-53 One
study evaluated tolterodine.54 One study evaluated
There is also a good body of literature addressing the flavoxate hydrochloride and imipramine.42 One study
effects of weight loss on incontinence specifically. The evaluated trospium.45
most definitive trial reported that a six-month
behavioral weight loss intervention resulted in an 8.0% The Panel interpreted these data to indicate that
weight loss in obese women, reduced overall behavioral therapies can result in symptomatic
incontinence episodes per week by 47% (compared to improvements similar to anti-muscarinics without
28% in the control group) and reduced urgency urinary exposing patients to adverse events. Evidence strength
incontinence episodes by 42% (compared to 26% in is Grade B because although the majority of studies
controls).40 were randomized trials and findings were generally
consistent across studies (both randomized and
One study evaluated fluid management and reported observational), most of the randomized trials were of
that a 25% reduction in fluid intake reduced frequency moderate quality, follow-up durations were short in
and urgency.46 The Panel notes that when attempting most studies (12 weeks) and sample sizes were small.
intake reduction, baseline intake levels must be
considered to determine whether reduction is Guideline Statement 7.
appropriate. There is also evidence from a study of
bladder training that reducing caffeine intake results in Behavioral therapies may be combined with
greater reductions in voiding frequency.47 pharmacologic management. Recommendation

Based on a limited literature, no single component of Discussion. (Evidence strength – Grade C;

behavioral therapy appears to be essential to efficacy, Benefits outweigh risks/burdens). Behavioral and
and no single type of behavioral therapy appears to be drug therapies are often used in combination in clinical
superior in efficacy. In comparing behavioral training practice to optimize patient symptom control and QoL.
that was administered with biofeedback, with verbal A limited literature indicates that initiating behavioral
feedback or self-administered using a pamphlet, all and drug therapy simultaneously may improve
three approaches had similar effects to reduce outcomes, including frequency, voided volume,
incontinence and increase bladder capacity.48 Patients incontinence and symptom distress.45, 54, 57-59 In
in the two feedback conditions, however, reported patients who are not adequately improved on
greater treatment satisfaction and better perceptions of behavioral or drug therapy alone, there also is evidence
symptom control, suggesting that feedback may be that continuing the initial therapy and adding the
alternate therapy using a stepped approach can

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Guideline Statements

produce additional benefit.60 In the Panel’s judgment dosing regimens (see Figure 1 for urgency urinary
there are no known contraindications to combining incontinence data).
pharmacologic management and behavioral therapies.
Evidence strength is Grade C because of the limited
evidence base consisting of relatively few trials, small
sample sizes, and limited follow-up durations.

Second-Line Treatments: Pharmacologic

Management

Guideline Statement 8.

Clinicians should offer oral anti-muscarinics, or

oral β3-adrenoceptor agonists as second-line
therapy. Standard

Discussion. (Evidence strength – Grade B;

Benefits outweigh risks/burdens). Anti-
muscarinic medications. The choice of oral anti-
muscarinics as second-line therapy reflects the fact that
these medications reduce symptoms but also can
commonly have non-life-threatening side effects such
as dry mouth, constipation, dry or itchy eyes, blurred
vision, dyspepsia, UTI, urinary retention and impaired
cognitive function. Rarely, life-threatening side effects
such as arrhythmias have been reported. An extensive
review of the randomized trials that evaluated
pharmacologic therapies for OAB (including trials with
placebo control groups as well as trials with active
treatment comparison groups) revealed no compelling
evidence for differential efficacy across medications.44,
51-54, 57, 61-125
This finding is consistent with the
conclusions of several published systematic reviews.126-
129

These data were not suitable for meta-analysis due to Figure 1. Baseline Urgency Urinary Incontinence
of lack of variance information (e.g., standard (UUI; episodes/day) and UUI Reduction
deviations, variances, standard error of the mean) for (episodes/day) for randomized trials by drug.
outcomes in many studies. Qualitative analysis
revealed, however, that for 24-hour frequency, urgency For urgency and nocturia, however, there was no
incontinence and incontinence, baseline symptom level apparent relationship between baseline symptom levels
was closely related to degree of symptom reduction and symptom reduction (See Figure 2 for urgency
across medications. Specifically, patients with more data).
severe symptoms, on average, experienced greater
Due to the similar efficacy observed for all oral anti-
symptom reductions. For urgency incontinence and
muscarinic medications, the choice of medication for a
total incontinence episodes, only patients with relatively
particular patient depends on the patient’s history of
low baseline symptom levels were likely to experience
anti-muscarinic use, information regarding adverse
complete symptom relief.
events experienced in the past, the impact on the
This relationship was evident both within and across patient of adverse events, patient preferences,
medications regardless of study inclusion criteria or comorbidities, use of other medications and the
availability of and resources to acquire specific

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Figure 2. Baseline urgency (episodes/day) and statistically indistinguishable with overlapping

urgency reduction (episodes/day) for randomized confidence intervals and derived from relatively few
trials by drug. trial arms for each medication; the Panel interpreted
these findings as preliminary and descriptive rather
than definitive until more data are available.

The majority of the available studies evaluated

oxybutynin (25 trial arms) and tolterodine (40 trial
arms). The rate of dry mouth for oxybutynin at 61.4%
was statistically significantly higher (95% CI: 52.5% to
69.5%) than the 23.7% rate for tolterodine (95% CI:
20.7% to 26.9%) (p<0.001). Although there was no
clear relationship with dose, there was heterogeneity
within each medication based on whether the
immediate release (IR) or the extended release (ER)
formulation was administered (see Guideline Statement
8 below).

With regard to constipation, on average 3.6% of

placebo patients experienced this adverse event (36
placebo arms; 95% CI: 2.7% to 4.8%). Constipation
rates in active drug treatment arms for fesoterodine
(11 arms), solifenacin (15 arms), and trospium (5
arms) ranged from 7.0% to 9.0%. These rates were
statistically indistinguishable with similar 95%
confidence intervals spanning 5.0% to 12.0%. The
constipation rate for darifenacin (9 arms), however,
was significantly higher at 17.0% (95% CI: 13.0% to
21.0%). Within each medication, there was no clear
relationship between rate and dose. Since these data
were derived from relatively few trial arms, the Panel
again interpreted them as descriptive rather than
definitive until more data are available.

The majority of the available studies evaluated

medications. In addition, although there was no
oxybutynin (21 trial arms) and tolterodine (34 trial
evidence of differential efficacy across medications,
arms). The rate of constipation for oxybutynin was
both qualitative analysis and meta-analysis of all
12.1% (95% CI: 7.9% to 18.0%). The rate for
randomized trial arms revealed different adverse event
tolterodine was statistically significantly lower
profiles for dry mouth and constipation.* This
(p<0.001) at 4.9% (95% CI: 4.1% to 5.7%). There
information may be relevant if a patient is particularly
were no differences based on dose or between the IR
sensitive to one of these adverse events.
and ER formulations for either medication.
With regard to dry mouth, meta-analysis revealed that
The Panel interpreted the oxybutynin and tolterodine
on average 6.90% of placebo patients experienced dry
data to indicate that the probability that a patient will
mouth (40 placebo arms; 95% CI: 5.6% to 8.5%).
experience dry mouth and/or constipation appears to
Rates of dry mouth in active drug treatment arms for
be higher overall with the administration of oxybutynin
the newer medications (i.e., darifenacin – 9 arms,
compared to tolterodine. See Guideline Statement 9
fesoterodine – 11 arms, solifenacin – 15 arms) and for
regarding the ER vs. IR formulations. Evidence
trospium (8 arms) ranged from 20.0% to 40.0%.
strength was Grade B because most trials were of
Within each medication, there was no clear relationship
moderate quality and follow-up durations were
between rate and dose. Across medications, rates were

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Guideline Statements

relatively short (i.e., 12 weeks). generally performed similarly to tolterodine. Higher

doses of mirabegron did not produce greater effects.
β 3-adrenoceptor agonists: Mirabegron. The update
literature review retrieved a newly-published set of Pooled analyses and meta-analyses. Nitti Khullar et
studies that evaluated the benefits and risks/burdens of al.137 (2013) reported findings from a pre-specified
mirabegron, a β3-adrenoceptor agonist, for overactive pooled efficacy and safety analysis using data from the
bladder. Seven studies evaluated mirabegron in USA/Canada Phase III trial,131 the Europe/Australia
comparison to a placebo group and/or an active control Phase III trial,130 and the Europe/USA/Canada Phase
group130,131,132, 133, 134,135, 136 in a total of 9,310 patients; III trial.132 Mirabegron at doses of 50 and 100 mg
5,884 of these patients were in the mirabegron groups. once daily significantly reduced incontinence episodes
For the five studies that used an active control group, per day (50 mg: -1.49 [95% CI -1.63 to -1.36]; 100
the active control was tolterodine ER 4 mg. Five mg: -1.50 [95% CI -1.67 to -1.34]) and number of
studies were Phase III trials evaluating safety and voids per day (50 mg: -1.75 [95% CI -1.89 to -1.61];
efficacy. One study was a Phase II proof-of-concept 100 mg: -1.74 [95% CI -1.91 to -1.56] compared to
study,136 and one study was a Phase II dose-ranging placebo incontinence episodes: -1.10 [95% CI -1.23 to
trial.135 Five studies followed patients for 12 weeks. -0.97]; voids per day: -1.20 [95% CI -1.34 to -1.06])
The proof-of-concept study followed patients for four at 12 weeks of treatment. Significant improvements in
weeks.136 One of the Phase III trials followed patients mean voided volume/micturition, mean level of
for one year.133 Inclusion criteria were similar across urgency, mean number of urgency episodes (grade 3 or
studies, generally requiring patients to have OAB 4)/day, mean number UUI episodes per day, and mean
symptoms for ≥ three months, ≥ eight voids/day, and number nocturia episodes per day also were noted for
at least three urgency episodes over a three-day both doses compared to placebo. The proportion of
period. Patient ages were similar across studies, patients reporting zero incontinence episodes was
ranging from mean 55.4 years to mean 61 years. All significantly higher in the mirabegron groups (50 mg:
studies used a two-week single-blind placebo run-in 44.1%; 100 mg: 46.4%) compared to placebo
period. Baseline symptom levels were remarkably (37.8%). Efficacy in patients who had used anti-
similar across studies, with baseline voids/24 hours muscarinics compared to treatment-naïve patients was
ranging from mean 10.9 to mean 12.3, baseline similar across doses. The 25 mg dose significantly
incontinence episodes ranging from mean 2.4 to 3.6 reduced frequency and incontinence episodes but
but with all but one study arm in the 2.4 to 3.0 range, generally not other endpoints. The 50 and 100 mg
and baseline UUI episodes ranging from 1.7 to 3.5 but doses also significantly improved ratings on the
with all but one study arm in the 1.7 to 2.7 range. Only Treatment Satisfaction-VAS compared to placebo.
two studies measured urgency episodes, and patients There was no dose-response gradient for the 50 mg
ranged from mean 4.1 episodes per day to mean 6.6 dose compared to the 100 mg dose with both doses
episodes per day.134,136 The same two studies also producing similar effects. Cui (2014)138 reported
reported nocturia outcomes; at baseline patients had findings from a meta-analysis as standardized mean
mean 1.7 to 2.1 episodes per night. differences (SMDs) between mirabegron groups
collapsed across dose and placebo groups. The SMDs
All studies focused on voids per day and incontinence were (statistically significant at p <0.05 unless
episodes. Some studies also reported urge urinary otherwise noted): number of incontinence episodes per
incontinence, urgency episodes, and nocturia. Most day: -0.44 (95% CI -0.86 to -0.12); voids per day: -
studies included some measure of QoL (e.g., Treatment 0.62 (95% CI -0.89 to -0.25); urgency episodes per
Satisfaction-Visual Analogue Scale, Patient Perception day: -0.60 (95% CI -0.85 to -0.36); nocturia episodes
of Bladder Condition, OAB-q). In general, most per day: -0.12 (95% CI -0.23 to -0.01); TS-VAS: 0.75
mirabegron doses produced statistically significant (95% CI 0.45 to 1.05; non-significant); OAB-q: -5.34
symptom reductions for voids per day and incontinence (95% CI -7.11 to -3.57); PPBC: -0.20 (95% CI -0.33 to
episodes per day compared to placebo. Improvements -0.07).
in UUI, urgency episodes, and QoL measures also
occurred but were not as consistently statistically Additional useful information is provided by a report
significant. Among studies with an active control group from the National Institute for Health and Care
administered tolterodine ER 4 mg/daily, mirabegron Excellence (NICE 2013) that evaluated the mirabegron

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

evidence in preparation for making recommendations to mirabegron groups (from 0.6 to 2.3 beats per minute
United Kingdom practitioners. 139 NICE performed a with increasing dose). In comparison, the tolterodine
mixed treatment comparison analysis – a Bayesian groups exhibited increases of 1.0 to 2.1 beats per
statistical procedure that combines data across trials minute. Rates of tachycardia were less than 5% in
and compares treatments that were never tested head- each group and comparable to placebo rates.
to-head. NICE concluded that all medications, including
mirabegron, have similar efficacy to reduce frequency. The meta-analysis reported by Cui138 (2014) indicated
With regard to incontinence episodes, mirabegron and that rates of hypertension, cardiac arrhythmias, and
other medications also were similar with the exception urinary retention in mirabegron-treated patients were
of solifenacin (5 and 10 mg), which was statistically indistinguishable from rates in placebo groups.
significantly more effective. However, NICE notes that Chapple133 (2013) reported adverse events during a 12-
the size of differences across medications was small. month trial of mirabegron (50 and 100 mg) compared
The Panel interpreted these findings to indicate that, in
general, mirabegron has similar efficacy to the anti- Selected Adverse Events (AEs)
muscarinics. From 12-month mirabegron trial*
Mirabegron Mirabegron Tolterodine
The pooled safety analysis of the three Phase III AE 50 mg 100 mg ER 4 mg
trials137 reported that overall rates of treatment- Any AE 59.7 61.3 62.6
emergent adverse events (TAEs) were similar across Hypertension 11.0 10.1 10.6
groups (Placebo: 47.7%; 25 mg mirabegron: 48.6%;
Cardiac arrhythmia 3.9 4.1 6.0
50 mg mirabegron: 47.1%; 100 mg mirabegron:
43.3%; tolterodine ER 4 mg: 46.7%) without evidence Corrected QT interval prolongation 0.4 0.2 0.4
of a dose-response relationship across the mirabegron
Constipation 2.8 3.0 2.7
groups. The incidence of serious adverse events was
similar across groups: placebo -2.1%; mirabegron 25 Dry mouth 2.8 2.3 8.6
mg – 1.6%; mirabegron 50 mg – 2.1%; mirabegron
UTI 5.9 5.5 6.4
100 mg – 2.8%; and tolterodine ER 4 mg – 2.2%. The
proportion of patients withdrawing from the studies for Dizziness 2.7 1.6 2.6
medication adverse events also was similar across *From Chapple (2013)
groups: placebo – 3.3%; mirabegron 25 mg – 3.9%;
mirabegron 50 mg – 3.9%; mirabegron 100 mg –
to tolterodine ER 4 mg. Rates of adverse events were
3.7%; and tolterodine ER 4 mg - 4.4%.
generally similar across groups with the exception of
Detailed adverse events are reported in Nitti, Khullar 137 dry mouth, which was higher in the tolterodine group.
(2013) (see table below). Generally, rates of adverse Blood pressure changes were minimal (< 1 mm Hg) as
events were similar across groups with the exception of were pulse rate changes (< 2 beats per minute). Below
dry mouth, which was higher for the tolterodine ER 4 are selected adverse events from Chapple133 (2013).
mg group. Changes in blood pressure and pulse rate
Additional useful information is provided by Malik
were minor and comparable across groups, although
pulse rate increases were dose-dependent across the

Selected Adverse Events (AEs) from Pooled Phase III Trials*

Mirabegron Mirabegron Mirabegron Tolterodine
AE Placebo 25 mg 50 mg 100 mg ER 4 mg
Dry mouth 1.6% 1.6% 0.9% 2.2% 9.5%

Constipation 1.4% 1.6% 1.6% 1.6% 2.0%

Hypertension 4.6% 6.9% 4.7% 3.4% 6.1%

Headache 1.3% 0.9% 2.0% 1.3% 2.2%

UTI 1.8% 4.2% 2.9% 2.7% 2.0%

*from Nitti, Khullar 2013

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

(2012), 140 which reports findings from a randomized, Clinicians should be cautious in management of these
double-blind, placebo- and active-controlled study of potentially vulnerable patient groups and engage in
mirabegron effects on cardiac repolarization in healthy regular monitoring for adverse events. Further, there is
volunteers. The active control was moxifloxacin. no information regarding whether patients are more
Continuous ECGs were recorded during crossover likely to adhere to mirabegron than to the anti-
treatment with once-daily 50, 100, or 200 mg muscarinics.
mirabegron or a single 400 mg dose of moxifloxacin
(each participant exposed to only one daily dose). Guideline Statement 9.
Mirabegron did not prolong the QT interval at the 50
If an immediate release (IR) and an extended
mg and 100 mg doses but did result in prolongation at
release (ER) formulation are available, then ER
the 200 mg dose in females only (>10 msec from 30
formulations should preferentially be prescribed
min post-dose to 6 hours post-dose).
over IR formulations because of lower rates of
The MTC presented by NICE (NICE 2013) further dry mouth. Standard
indicates that the probability of dry mouth and
Discussion. (Evidence strength – Grade B;
constipation were statistically indistinguishable for
Benefits outweigh risks/burdens). A meta-analysis
mirabegron compared to placebo. 139 All of the anti-
of adverse events indicated that the ER formulations of
muscarinics had a significantly higher probability of dry
oxybutynin and tolterodine resulted in statistically
mouth compared to mirabegron 50 mg. Mirabegron was
significantly fewer patient reports of dry mouth than
similar to most anti-muscarinics in terms of risk of
the IR formulations of both medications. Specifically,
constipation except for solifenacin (5 mg and 10 mg),
the rate for the oxybutynin ER formulation was 40.0%
fesoterodine (8 mg) and trospium (60 mg), all of which
(95% CI: 28.0% to 53.0%) and was statistically
had a higher risk of constipation.
significantly lower than the oxybutynin IR rate of
Overall, the Panel interpreted the mirabegron data to 69.0% (95% CI: 60.6% to 76.5%). The dry mouth
indicate that mirabegron appears to be similar in rate for ER tolterodine was 18.0% (95% CI: 14.8% to
efficacy to the anti-muscarinics and has lower rates of 21.4%) and was statistically significantly lower
dry mouth than any of these medications. Mirabegron (p<0.001) than the IR rate of 28.8% (95% CI: 25.1%
may produce lower rates of constipation than some of to 32.8%). Within each medication, there was no
the anti-muscarinics. This lower incidence of relationship with dose. There were insufficient trospium
bothersome adverse events may inform the selection of trial arms to meta-analyze the IR vs. ER formulations;
medications for patients who already present with dry however, a similar pattern was evident. The IR
mouth (e.g., secondary to Sjogren’s syndrome) and/or trospium trials reported dry mouth rates that ranged
constipation or for patients who experience efficacy from 19.8% to 41.4% of patients;45, 82, 102, 108, 123, 141 in
from the anti-muscarinics but cannot tolerate these contrast, the ER trospium trials reported dry mouth
adverse events. rates of 8.7 to 12.9%.77, 111

The body of evidence strength for the benefits and Because OAB is a chronic condition and treatment with
risks/burdens of mirabegron is Grade B. The available anti-muscarinics generally would be required long-term,
RCTs appear to have been well-conducted and optimizing medication tolerability is critical to obtaining
evaluated large numbers of patients. However, follow- patient compliance. Adverse drug events, particularly
up in most studies is limited to 12 weeks, the dry mouth, are the major reasons that patients fail to
magnitude of symptom reductions is relatively modest, comply with anti-muscarinic therapy; thus choosing the
and the patients in most trials cluster on the lower end formulation with the lowest likelihood of adverse events
of OAB symptomatology. These limitations result in may improve compliance.142, 143 In addition, compliance
uncertainty regarding long-term use of mirabegron in with a once-daily treatment has been shown to be
broader patient populations, particularly those with greater than with medications that are taken more than
more severe OAB symptoms. In addition, there are no once a day.133 The decision to prescribe an IR vs. an
data on the use of mirabegron in patients with ER formulation, however, should be made in the
significant comorbidities, such as cognitive context of the patient’s prior experience with anti-
impairments, glaucoma, or uncontrolled hypertension. muscarinics and the availability of medications,

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

including insurer constraints, in order to minimize group compared to a reduction of 0.21 episodes in the
patient burden. Insurer constraints may be such that a placebo group) and non-significant reductions in
patient may need to be prescribed an IR formulation frequency and UI episodes/day.147 The primary
and either have inadequate symptom control or have outcome in this trial was patient-selected goals for
intolerable side effects prior to obtaining approval to be treatment. A greater proportion of patients in the 3.9
prescribed an ER formulation. The Panel notes that if a mg group reported goal achievement (41.9%) than in
patient has good symptom control and tolerable side the placebo group (32.2%), but the difference was not
effects on an IR formulation, then there is no need to significant. The authors note that the relatively low
change to an ER formulation. proportions of patients who reported achieving
treatment goals may indicate why many patients
Guideline Statement 10. discontinue anti-muscarinic treatment. Homma and
Koyama (2006) compared 2.6 mg, 3.9 mg and 5.2 mg
Transdermal (TDS) oxybutynin [patch (now
TDS oxybutynin to placebo and reported reductions in
available to women ages 18 years and older
incontinence episodes of 1.5 episodes with 2.6 mg, 2.0
without a prescription)* or gel] may be offered.
episodes with 3.9 mg, 1.6 episodes with 5.2 mg and
Recommendation *Revised June 11, 2013
1.4 episodes with placebo.87 Baseline incontinence
levels were lower in this trial (average of 3 episodes/
Discussion. (Evidence strength – Grade C;
day) than in the Dmochowski (2002) trial (average of 4
Benefits outweigh risks/burdens). Transdermal
episodes/day), which might account for the smaller
preparations of oxybutynin may be offered instead of
magnitude of change. In patients known to be
oral anti-muscarinics to patients who are at risk of or
responsive to oral oxybutynin, Davila (2001) used 1.3
who have experienced dry mouth with oral agents. Six
mg to 3.9 mg TDS oxybutynin or 5 mg to 22.5 mg oral
randomized trials evaluated transdermal oxybutynin
oxybutynin, depending on the patient’s prior tolerance
preparations. Four trials that included placebo control
for oxybutynin.74 Reduction of approximately 4.8
groups evaluated the TDS patch.76, 87, 145, 147 One trial
incontinence episodes/day occurred in both groups.
with a placebo control group evaluated oxybutynin
Staskin (2009) evaluated 1 mg oxybutynin chloride
chloride topical gel.146 An additional trial compared the
topical gel and reported significant decreases in
oxybutynin TDS patch to oral oxybutynin. 74
urgency incontinence (3 fewer episodes/day) and
Dmochowski (2002) evaluated three oxybutynin doses
frequency (2.7 fewer episodes/day) compared to the
administered via TDS patch (1.3 mg, 2.6 mg and 3.9
placebo group (2.5 fewer UI episodes/day and 2 fewer
mg) and reported reductions in incontinence episodes
frequency episodes/day).146 Newman (2010) reported
per day (reductions of 2.8 episodes with placebo, 2.7
on the same patients and noted that treatment with gel
episodes with 1.3 mg, 2.6 episodes at 2.6 mg and 3.3
improved health-related QoL measures more than did
episodes at 3.9 mg) and reductions in 24 hour
treatment with placebo.148
frequency (reductions of 1.7 episodes with placebo, 1.8
with 1.3 mg, 1.8 with 2.6 mg and 2.3 with 3.9 mg);
Five trials reported adverse events. Dmochowski
only the reductions with 3.9 mg were significantly
(2002) reported dry mouth rates of 8.3% with placebo,
different from placebo.145 A 12-week open-label
4.6% with 1.3 mg TDS oxybutynin, 6.8% with 2.6 mg
extension of this study reported larger incontinence
and 9.6% with 3.9 mg and constipation rates of 3.0%
episode reductions, ranging from 3.4 to 3.9 episodes.
with placebo, 5.4% with 1.3 mg, 2.3% with 2.6 mg and
Dmochowski (2003) evaluated only the 3.9 mg dose
0.8% with 3.9 mg.145 Dmochowski (2003) reported dry
compared to r mg tolterodine ER and placebo in known
mouth rates of 4.1% with 3.9 mg TDS oxybutynin,
responders to anti-muscarinics and reported similar
7.3% with tolterodine and 1.7% with placebo;
findings for frequency for both the TDS and oral
constipation rates were 3.3% with 3.9 mg and 5.7%
medication groups.76 In addition, in this trial, urgency
with tolterodine (constipation rate not reported for
incontinence episodes were reduced by 2.8 episodes a
placebo group).76 Davila (2001) reported dry mouth
day using 3.9 mg compared to 3.2 episodes a day with
rates of 38% in the TDS group compared to 94% in the
tolterodine and 2.1 episodes a day with placebo.
oral oxybutynin group (constipation rates not
Cartwright (2010) also evaluated 3.9 mg compared to
reported).74 Cartwright (2010) reported that 38.2% of
placebo and reported significant reductions in urgency
patients in the active treatment group experienced
episodes/day (reduction of 1.23 episodes in the 3.9 mg
erythema or pruritus (compared to 27.1% in the

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

placebo group) and 14.9% experienced at least one Further, clinicians may also switch patients to a β3-
systemic adverse event, the most common of which adrenoceptor agonist (e.g., mirabegron) given an
was dry mouth (compared to 12.5% in the placebo efficacy profile that appears similar to the anti-
group).147 Staskin (2009) reported dry mouth rates of muscarinics and a relatively lower adverse event
6.9% in the oxybutynin gel group compared to 2.8% in profile.
the placebo group and rates of other adverse events at
1% or less in both groups.146 There is no literature that addresses combination
therapy of anti-muscarinics with each other, the
The Panel interpreted these data to indicate that combination of the anti-muscarinics with β3-
transdermal oxybutynin (patch and gel) is effective in adrenoceptor agonists, or the combination of anti-
reducing incontinence episodes, in particular, with dry muscarinics with other classes of medication such as
mouth rates that appear to be less than the meta- tricyclics to manage non-neurogenic OAB.
analyzed rates of 40.0% for oral oxybutynin ER and
68.0% for oral oxybutynin IR. Because the number of Guideline Statement 12.
studies evaluating TDS oxybutynin was relatively few
Clinicians should not use anti-muscarinics in
with different patient inclusion criteria (i.e., known
patients with narrow angle glaucoma unless
responders to anti-muscarinic medications in some
approved by the treating ophthalmologist and
trials), the body of evidence strength was designated as
should use anti-muscarinics with extreme caution
Grade C.
in patients with impaired gastric emptying or a
Guideline Statement 11. history of urinary retention. Clinical Principle

If a patient experiences inadequate symptom Discussion. Clinicians should not use anti-muscarinics
control and/or unacceptable adverse drug events in patients with narrow angle glaucoma unless the
with one anti-muscarinic medication, then a dose treating ophthalmologist approves and should use anti-
modification or a different anti-muscarinic muscarinics with extreme caution in patients with
medication or a β3-adrenoceptor agonist may be impaired gastric emptying or a history of urinary
tried. Clinical Principle retention, carefully weighing the benefits vs. the
significant risks. If the patient is at risk for or has a
Discussion. In the Panel’s experience, patients who history of gastric emptying problems, then the patient
experience inadequate symptom control and/or should be seen by or receive clearance from a
unacceptable adverse drug events with one anti- gastroenterologist. If the patient has a history of or is
muscarinic medication may experience better symptom at risk of urinary retention, then urology consultation
control and/or a more acceptable adverse drug event should be strongly considered. It is useful to obtain a
profile with another anti-muscarinic. In addition, in post void residual in any patient the clinician suspects
some patients, dose modification (i.e., reducing dose or has a higher than normal risk of urinary retention. Anti
reducing dose and combining medication with -muscarinics are also contraindicated in patients using
behavioral techniques) may achieve a better balance solid oral forms of potassium chloride, as the reduced
between efficacy and adverse drug events. A small gastric emptying potentially caused by the anti-
literature composed of observational studies supports muscarinics may increase the potassium absorption of
this experience, particularly when switching from an these agents. If these patients can be switched to
older medication to a newer medication. Patients who alternative forms of potassium chloride, then anti-
had prior unsatisfactory symptom control and/or muscarinic therapy may be possible with caution. In
unacceptable adverse events with tolterodine149-151 or weighing the risks of anti-muscarinic therapy in high-
oxybutynin151, 152 reported better efficacy and/or more risk patients, it is important to remember that OAB may
acceptable adverse event profiles with fesoterodine,149 compromise quality of life, but it is not a life-
solifenacin150, 152 or darifenacin.151 Based on the Panel’s threatening condition. Clinicians, therefore, should
clinical experience and this limited literature, the Panel exercise extreme caution in using treatments that may
advises that clinicians should not abandon anti- present life-threatening risks.
muscarinic therapy if trial of one medication appears to
fail or produces an unacceptable adverse event profile. Guideline Statement 13.

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

Clinicians should manage constipation and dry side effects. Providers also should exercise caution in
mouth before abandoning effective anti- patients who are prescribed acetycholinesterase
muscarinic therapy. Management may include inhibitors such as donepezil. This list is not intended to
bowel management, fluid management, dose be exhaustive; prescribers should be aware of
modification or alternative anti-muscarinics. precautions and contraindications for these
Clinical Principle medications.

Discussion. One of the main limitations of anti- In addition, most clinical studies of OAB medications
muscarinic therapy is that the majority of patients have been conducted on relatively narrow patient
discontinue after a few weeks or months.142, 144 populations and provide only short-term data (i.e., 12
Although there may be several factors involved in this weeks) on adverse drug events. In the absence of long
decision, side effects are commonly cited as the reason -term data on patients neither eligible for nor included
for discontinuation.143 One way clinicians can help in clinical trials, the prevalence and severity of adverse
patients benefit from anti-muscarinic therapy is to drug events is largely unknown.
proactively monitor for and manage common side-
effects. Even before initiating anti-muscarinic therapy, Guideline Statement 15.
patients should be educated about the possible effects
Clinicians should use caution in prescribing anti-
of medication on bowel function and the roles of
muscarinics or β3-adrenoceptor agonists in the
adequate dietary fiber and fluid, psyllium-based fiber
frail OAB patient. Clinical Principle
supplements, regular exercise and normal bowel habits.
Preparing for dry mouth might include advice on oral
Discussion. In frail patients, defined as patients with
lubricants, avoiding mouthwashes with alcohol, taking
mobility deficits (i.e., require support to walk, have
small sips of water, sucking on sugar-free hard candies
slow gait speed, have difficulty rising from sitting to
and chewing sugar-free gum. When dosing options are
standing without assistance), weight loss and weakness
available, dose reduction can provide relief from side-
without medical cause and who may have cognitive
effects while retaining some therapeutic effects. In
deficits153 (PR 37, 98, 315), the use of OAB medications
older patients who may metabolize drugs differently, it
may have a lower therapeutic index and a higher
is often advisable to start with a minimal dose and then
adverse drug event profile. OAB medication studies
increase it if it is tolerated well. With multiple drugs
generally are not conducted in the frail elderly,
available for OAB, trying alternate anti-muscarinics may
resulting in a lack of data in this group. In the Panel’s
identify a medication that the patient can more easily
experience, however, adverse drug events in addition
tolerate.
to the typically reported events of dry mouth and
constipation may occur, including impaired
Guideline Statement 14.
thermoregulation that can cause dangerous core
Clinicians must use caution in prescribing anti- temperature elevation. Clinicians should begin with the
muscarinics in patients who are using other lowest possible dose and increase doses slowly while
medications with anti-cholinergic properties. carefully assessing for the balance between symptom
Expert Opinion control and adverse events. The use of transdermal
anti-muscarinics should be monitored to ensure that
Discussion. The concurrent use of other medications the skin where the medication is applied remains intact.
with anti-cholinergic activity may potentiate the side
effects of the anti-muscarinic class of OAB medications. Cognitive deficits, particularly memory difficulties, have
These medications include tricyclic antidepressants, been reported in response to anti-muscarinics,132-156
those used in the treatment of Parkinsonism and other and clinical experience suggests that elderly patients
extra-pyramidal diseases and of Alzheimer’s disease, may be particularly prone to these adverse effects.
and include benzotropine, biperiden HCl, galantamine, There is some suggestion that the newer agents (e.g.,
rivastigmine and trihexyphenidyl HCl. Certain anti- darifenacin) are less likely to produce cognitive deficits
nausea medications and those with atropine-like in elderly patients than are the older agents, but the
properties, such as trimethaphan, methscopolamine literature is limited and the two-week drug
bromide and ipratropium, may also potentiate these administration period in these studies is not long
enough to yield definitive conclusions.157, 158 Kay

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

(2006) notes, however, that patients may not recognize present increasing risks to patients that must be
that memory deterioration has occurred, making it balanced with potential efficacy. Before a patient is
essential for the clinician, family members and exposed to these therapies, a comprehensive
caregivers to monitor for these effects.158 In addition, evaluation should be conducted to ensure that the
polypharmacy is common in community dwelling patient’s symptoms are attributable to OAB and not to
patients who are frail,159 placing them at higher risk for some other disease process that requires other kinds of
adverse drug events, including impaired cognition. In treatment and the patient’s desire for further treatment
dementia patients, anti-muscarinics should be used should be ascertained.
with extreme caution or may be contraindicated entirely
depending on the level of cognitive impairment. The Third-Line Treatments: In the patient who has failed
Panel further notes that presently there are no data on behavioral and pharmacologic therapies or who is not a
the use of β3-adrenoceptor agonists (e.g., mirabegron) candidate for these therapies, onabotulinumtoxinA
in the frail patient, the patient with significant therapy, PTNS, or neuromodulation may be offered.
comorbidities, or the patient on multiple medications. The Panel notes that use of these third-line therapies
The clinician should consider these possibilities in requires careful patient selection and appropriate
prescribing anti-muscarinics or β3-adrenoceptor patient counseling. Clinicians may offer the third-line
agonists to frail patients and reassess the balance treatments in any order and may offer the alternate
between benefits and risks/burdens with the patient, third-line treatment if a patient is refractory to the
caregiver and/or family on a regular basis and/or when initial treatment choice. The Panel notes that there is
functioning appears to change. In patients who cannot no literature that addresses using these therapies in
tolerate anti-muscarinics or for whom pharmacologic combination.
management is not appropriate, behavioral strategies
FDA-Approved
that include prompted voiding and fluid management
may be helpful.
Guideline Statement 17
Guideline Statement 16.
Clinicians may offer intradetrusor
onabotulinumtoxinA (100U) as third-line
Patients who are refractory to behavioral and
treatment in the carefully-selected and
pharmacologic therapy should be evaluated by an
thoroughly-counseled patient who has been
appropriate specialist if they desire additional
refractory to first- and second-line OAB
therapy. Expert Opinion
treatments. The patient must be able and willing
Discussion. The Panel defines the refractory patient to return for frequent post-void residual
as the patient who has failed a trial of symptom- evaluation and able and willing to perform self-
appropriate behavioral therapy of sufficient length to catheterization if necessary. Standard
evaluate potential efficacy and who has failed a trial of
Discussion. (Evidence strength – Grade B;
at least one anti-muscarinic medication administered
Benefits outweigh risks/burdens). The Panel
for 4 to 8 weeks. Failure of an anti-muscarinic
designated intradetrusor onabotulinumtoxinA treatment
medication may include lack of efficacy and/or inability
as a Standard in the thoroughly-educated and carefully-
to tolerate adverse drug effects. The Panel notes that
counseled patient with moderate to severe OAB
this definition is a minimum definition; individual
symptoms because a body of moderate-quality
clinicians and patients may decide that it is in the best
evidence indicated sustained improvements in voiding
interests of the patient to persevere with behavioral
and QoL outcomes and rates of adverse events that
and/or pharmacologic therapy for longer periods, to
could compromise quality of life or lead to serious
combine behavioral and pharmacologic therapies to
illness were less likely to occur with use of the FDA-
achieve better efficacy, or to try alternate medications
approved dose of 100U. The available literature on
before judging that a patient is refractory.
intravesical use of onoabotlinumtoxinA is reviewed
Behavioral therapies present no risks to patients and below; the Panel focused its deliberations on injections
medications present risks that cease when the into the detrusor specifically because most studies
medication is stopped. The remaining treatment levels assessed this injection location. There is insufficient
evidence at present to comment on the relative efficacy

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

of injections into other intravesical locations. patients but not in placebo patients.187 Two additional
papers reporting on the same group of patients noted
The original literature searches retrieved four improved scores in onabotulinumtoxinA patients on the
randomized trials with placebo control groups (reported King’s Health Questionnaire during the randomized trial
in five papers), two randomized trials without placebo as well as during an open-label extension study206 and
control groups and 15 observational studies without that quality of life improvements and improved
control groups that evaluated the effects of urodynamic parameters were restored in patients who
onabotulinumtoxinA in patients with non-neurogenic required repeat injections.207 In Kuo (2007), three
OAB who had inadequate symptom control with anti- months after injection of 100 U onabotulinumtoxinA,
muscarinics or intolerable side effects.184-205 All studies the proportion of patients reporting a status of excellent
reviewed evaluated onabotulinumtoxinA except for or moderately improved was 93% of the detrusor
one191 which evaluated abobotulinumtoxinA. Studies group, 80% of the suburothelial space group and 67%
varied in onabotulinumtoxinA dose and in injection of the bladder base group.189 These proportions
location. Doses of onabotulinumtoxinA are not dropped to 67% (detrusor), 47% (suburothelial space)
equivalent to doses of abobotulinumtoxinA. and 13% (bladder base) at 6 months and to 20%
(detrusor), 20% (suburothelial space) and 6.7%
The four RCTs with placebo control groups evaluated
(bladder base) at 9 months. Dmochowski (2010)
injections into the detrusor of 200 U
184,187
compared responses across a wide range of
onabotulinumtoxinA, 200-300 U
onabotulinumtoxinA doses (50 to 300 U) and reported
onabotulinumtoxinA,186 or 50-300 U
that doses of 100 U or greater were sufficient to reduce
onabotulinumtoxinA.185, 200 The randomized trials
urgency incontinence episodes and improve QoL
without placebo control groups injected 100 U
measures but without clear dose-response effects such
onabotulinumtoxinA into the suburothelial space, the
that doses above 150 U did not contribute additional
detrusor or the bladder base189 or injected 100 U
clinically-relevant symptom improvement.185 Additional
onabotulinumtoxinA into the bladder body, bladder
information on the same patients was provided by
body and trigone or bladder base and trigone.190
Rovner (2011).200 This paper reported that doses of ≥
Significant reductions in incontinence episodes184, 186, 190
100 U all resulted in significant improvement of OAB
and in urgency187, 189, 190 were reported in active
symptoms (i.e., reductions in UI episodes and
treatment groups (but not in placebo controls where
frequency) without clear dose-response effects.
included). Frequency data were less clear with
Findings also were broken out between patients with
reductions occurring in most active treatment groups
and without detrusor overactivity (DO); similar
(except for patients injected in the suburothelial space
improvements were reported in both groups.
in Kuo 2007 who experienced increased frequency) but
with a large range of reductions (e.g., from a non- The observational studies injected doses of
significant 1.3 episodes per day in Flynn 2009, to 6.1 onabotulinumtoxinA ranging from 100 – 300 U. Most
episodes per day in Sahai 2007, to 14.2 episodes per studies injected into the detrusor except for two
day in Kuo 2007 in the detrusor injected group).186, 187, studies, which injected into the detrusor and
189
To some extent this range may be related to the sphincter202, 192 and two studies,195, 196 which injected
inclusion of patients with different baseline frequency into the submucosa of the bladder wall. Jeffery (2007)
levels (e.g., patients in Flynn 2009 had baseline 24- injected 500 U of abobotulinumtoxinA into the
hour frequency of 10.5 episodes per day compared to detrusor.191 As a group, the observational studies
patients in Kuo 2007 who had 24-hour frequencies reported reductions in frequency, nocturia, pad use and
ranging from 17.8 to 29.8 episodes per day),186, 189 but incontinence; improvement in urodynamics parameters
the largest reductions were reported in Kuo (2007),189 and improvement in quality of life measures. Follow-up
which is the trial with the lowest onabotulinumtoxinA durations ranged from 1.5 weeks to 145 weeks. In the
dose (100 U). Flynn (2009) also reported reductions in longer studies, improvements diminished over time and
nocturia (0.5 fewer episodes/night) and in pad use (2.2 repeat injections were required to restore
fewer pads/day) at six weeks post-injection.186 In improvements. Gamé (2010) reported that in patients
addition, Sahai (2007) reported improvements in a who had up to five repeat injections to maintain
variety of urodynamic parameters and improved scores improvement, QoL improved after each injection.208
on the IIQ-7 and the UDI-6 in onabotulinumtoxinA

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Guideline Statements

The update literature review retrieved 27 new studies, maintained. Kuo (2011) compared injection of 100U
including five randomized trials with placebo control into the bladder body, bladder body plus the trigone,
groups,209,210,211,131,212 two randomized trials with active and the bladder base plus the trigone and found no
control groups (Kuo 2011 – compared 100U in three differences across injection sites in success rates (70 to
different injection sites; AlTaweel 2011 – compared 74% of patients in each group) or in reductions in
100U to 200U in the detrusor),213 and 20 observational urgency or UUI episodes.224
studies.214-233 Patient selection criteria were similar to
those in the prior evidence (e.g., patients with These outcomes occurred, however, in the context of
moderate to severe baseline levels of UUI, high rates of adverse events in the active treatment
incontinence, frequency, and urgency) and, in groups in some studies. Rates of UTIs ranged from
aggregate, the new randomized trials reported on 3.6% to 54.5% with four of the RCTS reporting rates
responses of 887 patients treated with of >40.0% and Dmochowski (2010) reporting that
onabotulinumtoxinA – more than double the number of rates generally increased with dose with rates ranging
patients in the active treatment groups from the prior from 33.9% to 48.1% across active treatment
randomized trials. The lack of long-term follow-up groups.185 The definition of elevated post-void residual
remains, with the largest trials reporting outcomes at (PVR) varied across studies from 100 ml to 400 ml with
12 weeks. A few trials reported additional outcomes at most studies defining an elevated PRV as 100 - 150 ml.
longer intervals (e.g., AlTaweel 2011 – nine months; It should be noted, however, that that the highest rates
Denys 2012 – 6 months);213,210 the general pattern is of of urinary retention were not necessarily reported in
diminishing effectiveness. With the exception of Kuo studies that used the lowest PVR thresholds. Rates of
(2011) who compared injection sites, most studies urinary retention were reported in 10 studies and
injected into the detrusor.224 In contrast to prior ranged from 0% to 43% with rates of 43.0% and
evidence, the most commonly used dose was 100U 30.0% reported in one RCT (elevated PVR defined as
rather than 200U. 200 cc)184 and one observational study (elevated PVR
defined as 250 cc),188 respectively. Rates of PVR
In general, most trials reported statistically significant increase were reported in 14 studies and ranged from
improvements in measured voiding outcomes (UUI, 0% to 75% with half of these studies reporting rates of
incontinence, frequency, urgency, nocturia, pad use) 43.0% or higher (Kuo 2011);224,184, 188, 190, 910, 195, 198
and in QoL outcomes compared to placebo groups. The proportion of patients who needed to perform self-
Fowler (2012)234 reported QoL data from the catheterization was reported in 20 studies and ranged
Dmochowski (2010)185 dose-finding trial and noted that from 0% to 43% with six studies reporting rates higher
the I-QoL and KHQ exhibited significant improvement than 20.0%.184, 185, 187, 191-194 Increased PVRs and the
compared to placebo for all groups administered 100U need for self-catheterization persisted for six to nine
or greater. Studies that measured urodynamics months in some patients.188, 191, 201 It should be noted,
parameters also reported improvements (e.g., in however, that Kessler (2009) examined QoL outcomes
maximum bladder capacity). Denys (2012)210 in women who had to perform self-catheterization post-
compared placebo to 50U, 100U, and 150U; at three onabotulinumtoxinA treatment compared to those who
months post-procedure, >50% improvement in urgency did not and found no differences in UDI-6 and IIQ-7
and UUI was reported by 30% of placebo patients, 37% scores.193 Bauer (2011) focused more broadly on side
of the 50U patients, 68% of 100U patients, and 58% of effects and interviewed patients (n = 56) who had been
150U patients (sample sizes were <30 in each group; administered onabotulinumtoxinA (100, 150 or 200 U)
only the 100U group was statistically significantly or abobotulinumtoxinA (500 U) regarding the
different from placebo). The 100U and 150U groups occurrence of gross hematuria, dry mouth, dysphagia,
exhibited significantly reduced frequency compared to speech problems, impaired vision and weakness of the
placebo and this reduction persisted for 30 days in the eyelids, arms, legs, torso and/or whole body.235
100U group and was still significant at 60 months for Approximately 54% of patients reported at least one
the 150U group. The number of patients who achieved side effect, including urinary retention (8.9%), gross
complete continence at three months was significantly hematuria (17.9%), UTI (7.1%), dry mouth (19.6%),
greater in the 100U group (55%) and the 150U group dysphagia (5.4%), impaired vision (5.4%), eyelid
(50%) compared to the placebo group (11%). At five weakness (8.9%), arm weakness (8.9%), leg weakness
months post-treatment, these differences were (7.1%) and torso weakness (5.4%). The authors note

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

that symptoms other than urinary retention and UTI 83.4%; elderly – 91.2%; younger – 88.9%) and at six
were transient and resolved without the need for months across groups (frail elderly – 44.9%; elderly –
further treatment. These data indicate, however, that 52.1%; younger – 49.4%). By 12 months post-
patients may experience neurological adverse events in injection, however, success rates among frail elderly
addition to the more commonly reported events of were significantly lower at 6.82% then rates for elderly
urinary retention and UTIs. (22.3%) and younger patients (23.1%) and cumulative
success rates (Kaplan-Meier analysis) also were
Additional useful information regarding efficacy and significantly lower at follow-up to 15 months post-
adverse events is provided by the large group of injection. Rates of acute urinary retention (AUR),
observational studies. straining to void, and hematuria were similar across
groups. Frail elderly, however, were more likely to
Diabetic patients. Wang (2013) reported on 48 type II
have a PVR >150 ml (60.7%) compared to elderly
diabetes mellitus (DM) patients compared to 48 non-
(39.7%) and younger patients (35.7%). Although the
diabetic age-matched control patients. These patients
difference in AUR rates was not significant, the recovery
were older, on average, than in the randomized trials
period to spontaneous voiding was longer in frail elderly
(DM patients mean age 73 years; non-DM patients
(median 3.5 months) compared to one and 0.5 months
mean age 72 y).233 All patients had UDS-verified DO.
for elderly and younger patients respectively. Frail
Patients received 100U onabotulinumtoxinA in the
elderly also were more likely to report generalized
suburothelial space and were followed at three and six
weakness (6.6%) compared to elderly (0%) and
months. At three months, frequency, UUI episodes,
younger patients (0%). Interestingly, the highest rates
and PPBC scores had improved similarly in both groups;
of UTI occurred among younger patients (28.6%) with
urgency episodes were reduced in both groups but not
lower rates among frail elderly (13.1%) and elderly
significantly. Success rates (defined as PPBC score
(9.5%).
improvement of two or more points) were statistically
similar at 56% for DM patients and 61% for non-DM Long-term follow-up: Kuo (2011), Chen (2012), and
patients and remained at 6 months. DO disappeared in Ke (2012) reported on the same group of 174 patients
56.3% of DM patients and 47.8% of non-DM patients. with IDO and UUI who received 100U
After the six months point, success rates began to onabotulinumtoxinA using various injection sites (e.g.,
decrease. However, the DM patients had significantly detrusor or suburothelial injection in bladder body and/
higher rates of large PVR volumes (60.4%) and general or bladder base including the trigone). Improvements
weakness (10.4%) compared to the non-DM patients of at least 2 points on the PPBC were designated as
(large PVR – 33.3%; general weakness – 0%). successes.224,226,227 At three months, success rates
were similar for males (79%) and females (80%), for
OnabotulinumtoxinA in the frail elderly patient. Liao &
patients aged 75 or older (80%) and younger patients
Kuo (2013) reported on 166 patients, including 61 frail
(79%), and similar across different injection sites.
elderly (mean age 75.8 years), 63 elderly without
Patients were monitored for adverse events for up to 24
frailty (mean age 75.7 years), and 42 younger patients
months. Adverse events included: acute urinary
(mean age 44.6 years).222 Frailty was defined as age
retention in 6.9%; PVR >150 ml in 46.6%; straining to
>65 years and three or more of the following:
void in 42%; gross hematuria in 9.8%; UTI in 15.5%;
unintentional weight loss, self-reported exhaustion,
and general weakness in 3.4%.
weakness, slow walking speed, low physical activity.
Frail patients averaged 1.6 comorbidities, and 5.7 Okamura (2013) reported on 17 patients (mean age 67
medications per day. All patients had IDO refractory to years) who received one injection of
medications and persistent UUI/urgency. Patients onabotulinumtoxinA 100U submucosally and were
received 100U of onabotulinumtoxinA injected into the followed every month for one year.228 Urgency
suburothelial space. At three months, significant episodes, UUI, and daytime frequency were significantly
improvement had occurred in UUI and PPBC scores for decreased up to 11 months post-injection. Measures of
all three groups and CBC and PVR also had increased QoL were significantly improved for eight to ten months
significantly for all three groups. Success rates post-injection. Scores on a GRA measure
(defined as improvement of two or more points on the demonstrated improvement above baseline for eight
PPBC) were similar at three months (frail elderly – months. Median time to failure was 11 months but

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements

women had longer intervals to failure (11.7 months) had a single injection without benefit -16.8%;
compared to men (7.2 months). Two patients had a secondary failure -- patients who had benefit from the
PVR >200 ml that resolved without the need for CISC. initial injection but not after two or more - 11.7%;
tolerability -- patients who stopped onabotulinumtoxinA
Granese (2012) reported on 68 female patients (mean for reasons other than efficacy (e.g., having to perform
age 56 years) who underwent an injection of CISC, urinary retention, recurrent UTIs) - 55.9% with
onabotulinumtoxinA 100U into the detrusor and were an additional 16 patients who had primary and
followed for 12 months.230 At baseline, patients had secondary failure also citing tolerability issues as a
moderately severe symptoms (9.5 urgency episodes/ reason for discontinuation. Tolerability issues consisted
day; 15.1 voids/day; 2.5 nocturia episodes/day; 5.7 of worsening symptoms (4.8%), need for CISC
incontinence episodes/day). Symptoms improved (49.2%), recurrent UTIs (36.5%), and unable to
markedly up to six months and then began to decay perform CISC (9.5%).
although at 12 months symptom levels had not yet
returned to baseline. The same pattern was evident Veeratterapillay (2014) reported on 125 patients
with some urodynamic parameters (e.g., bladder (median age 53 years, all with DO including a minority
compliance, detrusor contraction). QoL measures also of patients with neurogenic DO) who had two or more
exhibited long-term improvement. A subset of 20 onabotulinumtoxinA 200U injections (2 injections – 125
patients elected to have a second injection at 12 patients, 3 injections – 60 patients, 4 injections – 28
months and improvements in most measured patients, 5 injections – 14 patients, 6 injections – 3
parameters again occurred (follow-up to 3 months). patients, 7 injections – 3 patients, 8 injections – 2
PVR > 100 ml with lower urinary tract symptoms was patients).232 The overall median interval between
judged as indication for CISC. At one month post- injections was 14.4 months. Mean intervals between
injection, 35% of patients after the first injection and injections were: 17.6 months between injections 1 and
40% of patients after the second injection required 2; 15.7 months between injection 2 and 3; 15.4
CISC. At two months post-injection, 22% of patients months between injections 3 and 4; and, 11.6 months
after the first injection and 25% of patients after the between the 4th and all subsequent injections. Of the
second injection required CISC. At three months post- 125 patients, 17% did not respond to repeated
injection, 3% of patients after the first injection and 1% injections and opted for other treatments (e.g., long-
of patients after the second injection required CISC. term catheterization, SNS, surgery). Approximately
UTI rates were 6% (after first injection) and 5% (after 26% of patients developed PVR ≥ 150ml with 91% of
second injection) but resolved after month one. these episodes occurring with the first two injections
and all occurring within the first three injections.
Repeated injections: injection intervals, discontinuation Approximately 18% of patients developed recurrent
rates, and discontinuation reasons. Mohee (2012) UTI.
reported on 137 patients (mean age 57.3 years; all
patients had DO with a minority having neurogenic DO) Dowson (2012) reported on 100 patients, 63 of whom
with at least 36 months follow-up.231 At the beginning had two or more injections (53 had two, 20 had three,
of the study, patients with idiopathic DO were 13 had four, 10 had five, 5 had six, 3 had seven, 1 had
administered 200U of onabotulinumtoxinA (in the eight, 1 had nine and 1 had ten injections).216
detrusor); later the dose was reduced to 100U as Significant reductions in frequency, urgency, and UUI
published literature emerged indicating lower doses had were observed following each injection. The most
equivalent efficacy. Mean re-treatment interval was 8 common reasons for discontinuing injections were poor
months. Of 104 patients with idiopathic DO, 66% efficacy (13%) and the need for CISC (11%). CISC
(n=69) stopped treatment with onabotulinumtoxinA. was needed by 35% of patients after the first injection;
The only difference between patients who continued 21% developed UTIs. Acute urinary retention occurred
and those who discontinued was the presence of in one patient; two patients required indwelling
incontinence at baseline (patients more likely to catheters. One patient developed urosepsis after his
discontinue) and age (patients aged <50 years more third injection. Additional adverse events were bladder
likely to discontinue). Reasons for discontinuation were pain persisting >1 week (2 patients), flu-like symptoms
evaluated for the group as a whole (104 with IDO; 33 for 1 week (1 patient), transient arm paresthesia (1
with NDO); these were: primary failure -- patients who patient), and leg weakness (1 patient).

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Guideline Statements

Abeywickrama (2013) reported on 33 female patients urgency, UI, and on QoL measures. CISC was required
(mean age 59.3 years) with IDO who had up to three after 16.8% of procedures (some patients had more
injections of abobotulinumtoxinA. 214 Patients received than one injection), was discontinued after three weeks
500U which was increased to 750U if symptoms in four cases, after three months in five cases, but the
returned within six months; location of injections was remaining seven patients “continue to self-catheterise 5
not specified. After each injection, significant -24 months following onabotulinumtoxinA treatment
improvements occurred in frequency, nocturia, mean (median 11 months).”
voided volume, and maximum voided volume. Scores
on the ICIQ also improved after each injection. The OnabotulinumtoxinA vs. abobotulinumtoxinA:
mean interval between the first and second injections Ravindra (2013) reported on 207 patients (detrusor
was 15.2 months and between the second and third injections including the trigone), 101 treated with
injections was 19.2 months (statistically significantly onabotulinumtoxinA (200U) and 106 treated with
longer). About 10% of patients required CISC (3 of abobotulinumtoxinA (500 U initially later dropped to
33); two patients developed UTIs after each injection. 300U).229 Both forms significantly reduced daily
frequency, nocturia, and incontinence episodes. Patient
More information regarding adverse events: Jackson
groups reported similar global improvement rates (81%
(2012) reported on 94 patients who had 200U of
of onabotulinumtoxinA group; 90% of
onabotulinumtoxinA injected into the detrusor. 220
Patients with IDO had similar success rates (81%) as abobotulinumtoxinA group). Therapeutic effects had
patients without IDO (89%) (success defined as patient similar durations (mean 10.7 months in
reporting symptom improvement). Post-injection, 29% onabotulinumtoxinA group; mean 10.9 months in
of patients required CISC. Kanagarajah (2012) abobotulinumtoxinA group). However, adverse event
reported on 32 patients without IDO, 19 of whom had rates differed significantly between the two
OAB-dry and 13 of whom had OAB-wet.221 Patients had preparations. Among onabotulinumtoxinA patients,
100U or 150U of onabotulinumtoxinA injected into the 23% required CISC compared to 42% of patients
detrusor. QoL measures improved significantly by 3 administered abobotulinumtoxinA. Among patients
months post-injection (UDI-6, VAS scale). Frequency
who received 300U abobotulinumtoxinA, the CISC
improved significantly among OAB-dry patients; UUI
rate was 46%; the rate in the 500U group was 37%.
improved significantly among OAB-wet patients,
dropping by more than 50%. Three patients who
Patient satisfaction: Brubaker (2012) reported on the
received 150U and one patient who received 100U
same patients evaluated in Dmochowski (2010; the
developed large PVRs and required CISC. Five patients
dose-finding trial in the current guideline).215
developed UTIs.
Responses on the PSTQ and assorted global assessment
measures indicated that greater proportions of patients
Injection location: Manecksha (2012) reported on 22
in the onabotulinumtoxinA groups attained their
patients randomized to trigone-including vs. trigone-
primary OAB treatment goal (34.5% to 65.3%)
sparing injections of 500U abobotulinumtoxinA into
compared to those in the placebo group (23.7%). El-
the bladder wall.223 Patients were followed for up to 26 Azab (2013) reported on 31 patients who had either
weeks. Both groups exhibited improvement on the onabotulinumtoxinA injections (100 or 200U into the
OABSS at 12 and 26 weeks; the urgency subscale also detrusor) or augmentation ileocystoplasty (AC) for
showed improvement at 6, 12, and 26 weeks. The size refractory idiopathic OAB. Treatment satisfaction was
of the improvement, however, was greater in the measured with the OAB-SAT-q at three and six months
trigone-including injected group. No patients post-procedure. The AC patients had significantly
developed vesicoureteral reflux and magnitude of PVR higher OA B-SA T-q scores than did t he
increase and rates of CISC (2 patients in each group) onabotulinumtoxinA patients. OnabotulinumtoxinA
were similar. patients cited the need for repeat treatments to
maintain symptom control as a primary reason for
AbobotulinumtoxinA. Irwin (2013) reported on 73
dissatisfaction. Makovey (2011) reported on 85
patients administered 250U of abobotulinumtoxinA into
patients who had 150 or 200U onabotulinumtoxinA
the detrusor and suburothelium.218 Significant
injected into the detrusor.225 All patients had failed
improvements were documented in frequency, nocturia,

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Guideline Statements

anticholinergic medications either for lack of efficacy Panel notes that at the FDA-approved dose of 100U
(57 patients) or because of intolerable side effects (28 some adverse events appear to occur less frequently.
patients). Success was defined based on patient- For example, rates of urinary retention in study arms
reported symptomatic improvement and was more that administered 100U were <20% compared to up to
likely to occur in patients who could not tolerate 43% in study arms administering higher doses.
medication side effects (86%) compared to patients Similarly, the percent of patients requiring CISC who
who did not experience medication efficacy (68%). were administered 100U was generally less than 10%
compared to up to 43% in studies using higher doses.
Presence of antibodies. Hegele (2011) reported on the The Panel judged that the benefits of
presence of antibodies post onabotulinumtoxinA onabotulinumtoxinA at the 100U dose in the carefully
injection in 31 patients.219 Eleven patients were treated counseled patient outweigh its risks/burdens and
once, 16 were treated twice, and four were treated designated it a Standard. The Panel notes that patients
three times. Blood was collected before and three considering onabotulinumtoxinA treatment must be
months post injection. In five patients (16%) counseled regarding the possible need to perform self-
onabotulinumtoxinA antibodies were detectable. One of catheterization for long periods (or to have a caregiver
these patients had a strongly positive titer and perform catheterization) and should be willing to accept
experienced complete failure of the treatment. The this possibility. OnabotulinumtoxinA treatment also
other four had slightly positive titers; one patient had a may require access to a clinician who can measure PVR
poor response to the second injection. Authors on a periodic basis if necessary. Further, effects
speculate that the presence of antibodies is involved in diminish over time for most patients; therefore,
poor treatment responses. patients also should be informed that repeat injections
are likely to be necessary to maintain symptom
Systematic review. Cui (2013) reports a systematic
reduction. The Panel also believes that this procedure
review and meta-analysis of 12 randomized
should be performed by experienced personnel familiar
onabotulinumtoxinA trials for idiopathic OAB.236 Their
with intravesical injection techniques.
meta-analysis indicates that in trials that measured
incontinence (Flynn 2009, Sahai 2009, Tincello 2012), Evidence strength is Grade B given a body of evidence
the mean difference in incontinence episodes between constituted by randomized trials. Limitations of the
onabotulinumtoxinA-treated patients (any dose) and available evidence include short follow-up durations in
placebo patients is -3.85 (95% CI -4.79 to - the best-designed studies (ranging from 4 to 12 weeks
2.90).186,187,212 The mean difference in frequency in for the RCTs), the variability in doses and injection sites
trials that reported that outcome (Flynn 2009, Sahai across studies, and adverse event reporting that was
2009) between onabotulinumtoxinA-treated patients variable.
and placebo-treated patients is -5.13 (95% CI -7.86 to
-2.39).186,187 The relative risk ratio for CISC in Guideline Statement 18
onabotulinumtoxinA-treated patients compared to
placebo-treated patients (based on data from Brubaker Clinicians may offer peripheral tibial nerve
2008, Denys 2012, Flynn 2009, Fowler 2012, Sahai stimulation (PTNS) as third-line treatment in a
2009, Tincello 2012) was 5.25 (95% CI 2.47 to carefully selected patient population .
11.16).184,210,186,234,187,212 The relative risk ratio for UTI Recommendation
(using data from Brubaker 2008; Denys 2012; Flynn
Discussion. (Evidence strength – Grade C; Balance
2009; Fowler 2 0 12 ; T i nc e l l o 2012) in
between benefits and risks/burdens uncertain In
onabotulinumtoxinA-treated patients compared to
the original literature review, eight studies reported in
placebo-treated patients was 2.36 (95% CI 1.58 to
ten publications assessed the efficacy of PTNS to treat
3.53). 184,210,186,234,212
OAB symptoms.103, 109, 174-181 The majority of studies
The Panel interpreted these data to indicate that were single-group observational designs that evaluated
onabotulinumtoxinA injections can improve moderate to patients with refractory OAB symptoms. Patients in
severe OAB symptoms in the context of adverse events these studies are characterized by having moderately
that could require secondary intervention (e.g., an severe baseline levels of incontinence (ranging from 2.2
untreated UTI, undiagnosed urinary retention). The to 9.8 episodes per day) with most studies assessing

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Guideline Statements

patients with more than 3 episodes a day. Patients had most studies having fewer than 25 patients in each
moderately severe frequency symptoms at baseline, treatment arm.
ranging from 11.8 to 16.5 episodes per day. Most trials
report improvements in all measured symptoms, The best quality evidence comes from Finazzi-Agro
including incontinence (typical reductions of 1 to 3 (2010), a double-blind RCT (placebo arm received
episodes/day), frequency (reductions of 2 to 5 stimulation for 30 sec in the gastrocnemius and the
episodes/day), nocturia (reductions of 1 to 2 episodes/ device was then turned off; all patients were told they
night) and quality of life. The most common protocol may not experience sensation during treatment).237
was the application of 30 min of stimulation once a PTNS patients had twelve 30-minute sessions three
week for 12 weeks (the trial duration; for continued times a week; placebo patients had the same number
benefit, weekly stimulation would have to continue). and duration of sessions but with only 30 sec of active
Peters (2009) compared PTNS to tolterodine ER 2-4 mg current in the alternate muscle location. Patients in the
daily and reported similar improvements in both groups PTNS group, but not in the placebo group, experienced
in voiding parameters but a greater proportion of statistically significant improvements in incontinence,
patients in the PTNS group indicating subjective frequency, voided volumes, and I-QoL scores. In the
improvement.103 Sancaktar (2010) compared PTNS group, 71% were characterized as responders
tolterodine ER 4 mg daily with and without PTNS and (defined as experiencing at least a 50% reduction in
noted that the combined treatment group improved UUI episodes) compared to 0% in the placebo group.
more than did the tolterodine alone group.109 Two In Souto (2014), patients were randomized to three
reports followed patients for long periods of time (44 groups: PTNS, oxybutynin ER 10 mg/daily, and PTNS +
weeks in Klingler 2000; 52 weeks in MacDiarmid 2010 oxybutynin ER 10 mg/daily.238 PTNS patients had
– a long-term report on patients initially evaluated in treatments twice a week, for 30 min, for 12 weeks. At
Peters 2009) and indicate that improvements were 12 weeks, all three groups showed similar
maintained as long as the treatment was improvements in frequency, incontinence, nocturia,
maintained.103, 174-176 Additional studies did not report ICIQ-SF scores, ICIQ-OAB scores, and symptom bother
raw voiding data but reported improvements in scores. The authors followed patients after treatment
symptoms and quality of life with treatment182, 183 that cessation for another 12 weeks. At week 24, the
ceased when treatment ceased.182 The validity of PTNS oxybutynin group had significantly worse scores
treatment responses is supported by Peters (2010), compared to week 12 on the QoL measures – but not
which compared a PTNS group to a sham-PTNS group the two groups that had PTNS. Frequency,
and found that only the active treatment group incontinence, and nocturia data at 24 weeks were only
exhibited improvements in frequency, nocturia and reported as proportions of patients exhibiting these
urgency incontinence. Adverse events were relatively symptoms; it appears that the oxybutynin only group
uncommon and mild. had decaying responses compared to the PTNS groups.
Three additional observational studies (Ugurlucan
The update literature search retrieved eleven new 2013; Zhao 2011; Onal 2012) generally reported
publications that reported outcomes from nine studies, improvements in voiding parameters and QoL outcomes
including one RCT (Finazzi-Agro 2010),237 one after five to 12 weeks of treatment. 242,243,244
randomized design (Souto 2014),238 and seven
observational designs. Patient inclusion criteria remain Treatment effects duration. Several studies focused on
varied with some studies requiring frequency and documenting the duration of treatment effects once
nocturia and others requiring UUI. Although most treatment ceased (e.g., Marchal 2011; Sherif &
studies reported outcomes at 12 weeks, several Abdelwahab 2013; Arrabal-Polo 2012).245,246,247 Using
reported longer-term findings. Peters (2013a, 2013b) protocols that ranged from 12 weekly sessions to a
reported findings in a group of responders from the protocol that used tapering session frequency over five
SUmiT trial who continued with PTNS therapy for up to to six months, these studies generally reported that
36 months.239,240 Yoong (2013) reported one-year treatment benefits were retained for four to six months
findings for a group of PTNS responders.241 Several once treatment ceased.
other papers reported partial findings beyond the
Longer-term outcomes in patients who undergo
formal study end date (see text below). Sample sizes
maintenance treatments. Peters (2013a, 2013b)
remained relatively small (range 14 to 60 patients) with

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Guideline Statements

reported long-term outcomes for PTNS responders 1.69 to 29.17); that is, PTNS patients were seven times
identified during the SUmiT trial who were willing to more likely to report success compared to placebo
continue with therapy.239,240 Patients in the SUmiT trial patients. In an analysis that included prospective non-
(Peters 2010) had 12 weekly PTNS treatments.248 randomized trials, the pooled subjective success rate in
Responders received PTNS therapy in sessions that PTNS patients was 61.4% (95% CI 57.5% to 71.8%;
tapered during a transition phase: two treatments at differing definitions of success) and the pooled
14-day intervals, two treatments at 21-day intervals; objective success rate (based on voiding parameters
one treatment at a 28-day interval. After tapering, but also with different definitions of success) was
patients had a customized treatment plan in which 60.6% (95% CI 49.2 to 74.7%). In trials that
PTNS sessions were prescribed based on patient report compared PTNS to anti-muscarinics, there were no
of increasing OAB symptoms. Throughout the 36 differences in efficacy. The authors conclude that PTNS
month follow-up period, patients reported significant significantly improves OAB symptoms, that the effects
improvements in frequency, nocturia, urgency are similar in magnitude to anti-muscarinics, but that
episodes, and UUI. Scores on the OAB-q and HRQoL as PTNS has a better adverse event profile. The primary
well as symptom severity scores also remained weakness identified by this group of papers is the lack
significantly improved. Among study completers, of long-term follow-up in a randomized design.
patients received a median of 1.0 treatments per
month (IQR 0.9 to 1.2) with 41% receiving <1 The Panel interpreted these data to indicate that PTNS
treatment/month, 55% receiving 1.0 to <2.0 can benefit a carefully selected group of patients
treatments/month, and 4% receiving 2.0 to <3.0 characterized by moderately severe baseline
treatments/month. incontinence and frequency and willingness to comply
with the PTNS protocol. Patients must also have the
Yoong (2013)241 also reported long-term follow-up data resources to make frequent office visits both during the
on a group of PTNS responders originally discussed in initial treatment phase and to obtain maintenance
Yoong (2010).249 Of the original 30 patients who treatments in order to achieve and maintain treatment
reported positive responses defined as OAB symptoms effects obtain treatment because treatment effects
no longer dominant, 50% reduction in frequency, and dissipate once treatment ceases. Reported adverse
25% reduction in IIQ-7 scores, 23 continued to receive events were minor; the most frequently reported
maintenance treatments (30 min sessions). The events were painful sensation during stimulation that
sessions were scheduled by the patients when they felt did not interfere with treatment and minor bleeding at
they needed a treatment. At two years, frequency, the insertion site. In the Panel’s view, benefits
UUI, nocturia, pad use, and IIQ-7 scores were outweigh risks/burdens for the use of PTNS in the
statistically indistinguishable from those recorded after thoughtfully-selected and counseled patient who is
initial responses to treatment, indicating treatment highly-motivated to make the required office visits.
effects had been maintained. Patients received a
median 8.42 treatments per year and median time As a group, the PTNS studies constitute Grade C
between treatments was 64.3 days. evidence because of the predominant observational
designs, varying patient inclusion criteria, small sample
Systematic reviews and meta-analyses. Since the sizes, and short follow-up durations for most studies.
completion of the original guideline, five systematic
reviews assessing PTNS have been Guideline Statement 19.
published.250,251,252,253,254 In general, these reviews
Clinicians may offer sacral neuromodulation
conclude that there is convincing evidence for the
(SNS) as third-line treatment in a carefully
efficacy of PTNS in comparison to placebo or sham
selected patient population characterized by
conditions, that from 37% to 100% of patients are
severe refractory OAB symptoms or patients who
reported to meet criteria for success (but success
are not candidates for second-line therapy and
criteria varied across studies), and that adverse events
are willing to undergo a surgical procedure.
are minimal. Burton (2012) also provided a meta-
Recommendation
analysis.251 When the randomized trials with placebo or
sham control groups are considered, the relative risk
Discussion. (Evidence strength – Grade C;
ratio (RR) for successful treatment is 7.02 (95% CI
Benefits outweigh risks/burdens). In the original

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Guideline Statements

literature review thirteen studies, predominantly single- approval study that included a subsample of patients
group observational designs, evaluated sacral randomized to SNS or to standard medical therapy
neuromodulation in patients with severe refractory OAB (SMT; anti-muscarinic medications).255 The study used
symptoms, many of whom had failed multiple other a less invasive procedure than in older studies and also
therapies.160-172 In general, patients were characterized used the newer tined lead. A total of 147 patients were
by extremely severe levels of baseline incontinence, randomized (SNS – 70; SMT – 77) and 130 patients
ranging from 5.0 to 11.6 episodes per day, by severe completed six months of treatment (SNS – 59; SMT –
frequency (most studies reporting baseline levels of 71).
more than 13 episodes per day) and by pad use of
more than 4 per day at baseline in most studies. This Siegel (2014) differs from the studies discussed above
group of studies is characterized by much longer follow- in that patients had less severe symptom levels at
up durations than in other OAB studies, with follow-up baseline (SNS: mean 11.2 voids/day; mean 2.4
ranging from 24 weeks to 260 weeks and most studies incontinence episodes/day, mean 1.1 pads/day; SMT:
following patients for more than a year. In general, mean 11.9 voids/day, mean 2.7 incontinence episodes/
studies reported that all measured parameters, day; mean 1.5 pads/day).255 In addition, the primary
including QoL and subjective improvement, show outcome was OAB therapeutic success defined as
improvement with treatment and that improvement ≥50% improvement in average incontinence episodes/
dissipates if treatment ceases. Siegel (2000), Janknegt day or voids/day or a return to normal voiding
(2001) and van Kerrebroeck (2007) evaluated the frequency of <8 voids/day rather than change in voids
same groups of urgency incontinence patients or incontinence episodes. At 6 months, the OAB
compared to urgency-frequency patients and reported success rate was 61% in the SNS group compared to
that at 5 years post-surgery greater than a 50% 42% in the SMT group (p=0.02). In addition, <8
improvement was reported by 68% of the UI group and voids/day was achieved by 61% of SNS patients
56% of the urgency-frequency group.163, 168, 171 Groen compared to 37% of SMT patients (p=0.04). The SNS
(2011) reported that treatment success (defined as ≥ group also improved more on the OAB-qol than did the
50% decrease in the number of daily incontinence SMT group (p<0.001), SNS female patients reported a
episodes or pads used) was 87.0% of patients at one greater improvement in sexual function than did SMT
month post-surgery with a decline to 62.0% at five female patients (p<0.05), and the SNS group exhibited
years.161 An additional study reported on urodynamics greater improvements in Beck Depression Inventory
outcomes for patients evaluated by Schmidt (1999) and scores than did the SMT group (p=0.01). However,
noted that patients with UI, with and without detrusor limited information is reported regarding the
overactivity, had similar improvements in urodynamic intervention content of the SMT arm; the report notes
parameters.167, 173 Leong (2011) assessed long-term only that 96.1% of SMT participants used OAB
satisfaction with SNS and reported that 90% of 207 medications between randomization and the six month
patients surveyed reported being satisfied with the follow-up, that 70% used medication on at least 80% of
treatment (median post-implant interval of 77 the days during the follow-up period, and that some
months).165 In an effort to reduce adverse events and participants (proportion not specified) used more than
possibly limit nervous system adaptation and one medication. Lack of information regarding
diminished efficacy that may occur with continuous medication use and that fact that patients had mild
stimulation, Oerlemans (2011) tested an on-demand symptoms compared to most other SNS studies limits
protocol in which patients turned the apparatus off for the interpretability of SMT outcomes compared to SNS
several hours a day.166 Approximately 63% of patients outcomes.
were able to maintain symptom improvement by using
The crossover study evaluated whether different
the on-demand procedure during the two-week test.
stimulator settings altered outcomes.256 Patients in this
The updated literature review retrieved an additional 16 study had had an SNS implant with a tined lead for at
relevant treatment studies, including one prospective least 3 months prior to study beginning and were
randomized multi-center trial,255 one crossover refractory to conventional treatments including
study,256
and 14 observational studies. Seigel (2014) medications at the time of SNS implant. Settings were
reported findings at six months of follow-up for the 5.2 Hz, 14 Hz, or 25 Hz and were maintained for one
InSite trial, an ongoing FDA-mandated post device week. Numbers of incontinence episodes and pad

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Guideline Statements

changes were significantly affected by rate such that decreases in urgency episodes, UUI, frequency,
the 14 Hz and 25 Hz settings reduced these outcomes nocturia, and in the severity of urgency episodes.262
compared to the 5.2 Hz setting. Various urodynamics parameters also improved as did
scores on the OAB-q. Improvements were similar for
The observational studies evaluated a wide range of patients with OAB-wet compared to OAB-dry. Yih
patient subgroups, clinical questions, and outcomes. (2013) reported on changes in sexual functioning in
More than half of the studies followed patients for one women after SNS implant.263 At 12 months post-
year or longer. implant, FSFI scores improved significantly from mean
13.5 at baseline to mean 15.9 and ICSI-PI composite
Testing phase outcomes. Davis (2013) reported success
score improvements were similar among women with
rates during the testing phase in patients who
baseline FSFI scores of < 26 compared to ≥ 26.
presented for SNS because of lack of medication
efficacy or intolerable medication side effects.257 Older patients. Angioli (2013) reported in patients >age
Success rates at the testing phase were similar (70% 65 years (mean patient age 76 years) that at 12
and 71% respectively). Yazdany (2011) also reported months post-implant, 27.8% of patients reported
on testing phase success in a group of patients with improvement and 55.5% of patients reported complete
severe incontinence (mean 10.4 episodes/day); the success with cessation of UUI episodes.264 Overall, UUI
authors note that patients with >10 incontinence episodes decreased from mean 6.3/day to mean 0.5/
episodes per day were more likely to have a successful day. Incontinence episodes, frequency, nocturia, and
stage I trial compared to those with less than 5 number of pads used daily also significantly decreased.
episodes/day.258 Levin (2012) reported on the impact of All subscales of the OAB-q exhibited significant
obesity on stage I success rates.253 Of 149 patients, 80 improvement. Peters Killinger (2013) compared
(53.7%) were obese (BMI mean 37.3) and 69 (46.3%) patients aged 40 to 64 years with patients older than
were non-obese (BMI mean 25.6). The overall stage I age 64.265 Most of the patients in these two groups had
success rate was 81% and the success rates for non- OAB (a subset had IC or urinary retention). For both
obese patients (83%) was statistically indistinguishable groups, incontinence episodes, frequency, urgency,
from the success rates for obese patients (78%). nocturia, OAB-q scores, and ICSI-PI scores improved
Gleason (2013) reported on stage I SNS effects on significantly at 26 weeks.
periurethral sensation and urethral sphincter activity.259
Baseline urethral sensation did not differ between Patients with concomitant bowel dysfunction.
patients who were classified as stage I responders vs. Faucheron (2012) evaluated patients with both urinary
non-responders, however, responders had larger and fecal incontinence.266 At more than 5 years post-
amplitude, longer duration, and more turns and phases implant, UUI episodes (and fecal incontinence episodes)
at baseline, indicating more successful urethral re- were significantly reduced. Approximately 74% of
innervation, than did non-responders. patients were satisfied with their improvements in both
forms of incontinence and all QoL measures also
Treatment phase outcomes. Lee (2013) compared exhibited significant improvement (e.g., the Fecal
motor and sensory responses to SNS and noted that Incontinence QoL measure and the Ditrovie score). Gill
patients with compound muscle action potential (cMAP) (2012) reported on patients with UUI of which 83% had
were more likely to report the sensation of stimulation concomitant bowel dysfunction (either constipation or
than patients without cMAP.260 Nineteen of 31 patients fecal incontinence).267 At 4 months post-implant, Likert
did not have cMAP. Of these, 16 were successfully scale ratings (patient perception of disease) were
reprogrammed to achieve cMAP, resulting in significantly improved from baseline and indicated that
improvements in nocturia, incontinence, and UI that did symptom severity and disease state had become
not reach statistical significance. Cardarelli (2012) “normal.” UDI-6 and CRADI-8 scores also reflected
reported significant decreases in UUI episodes, significant symptom improvement. When patients were
frequency, nocturia, and pad use as well as significant examined separately based on type of bowel
increases in voided volumes at 48 weeks post- dysfunction, the improvement in scores appeared to
implant.261 Moon (2013) evaluated patients with occur for the constipation group rather than the
severe levels of UUI, frequency, and nocturia and incontinence group.
reported at 12 months post-implant significant

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Guideline Statements

Patients who discontinued onabotulinumtoxinA. Smits underwent >14 days of staged testing, 50% developed
(2013) reported on a group of patients who had connector and/or lead colonization. In contrast, only 4
discontinued onabotulinumtoxinA therapy because of (14%) of the 28 patients who had ≤ 14 days of testing
lack of efficacy (85%) or the desire for a treatment that developed colonizations.
was more permanent (15%).268 The primary outcome
was improvement in leakage, defined as greater than Cameron (2013) reported on reprogramming and
50% improvement in leakage episodes and severity of battery explant rates from 1997 to 2007 in a 5%
leakage measured on a 1 to 4 scale. Secondary sample of Medicare beneficiaries at mean follow-up
outcomes were improvement in frequency and urgency 60.5 months.270 Among OAB-wet patients and OAB-dry
defined as greater than 50% improvement patients, during the first year there were mean 2.14
(measurement not specified but presumably also on a 1 and 2.26 reprogramming events respectively.
to 4 scale). Mean interval between last Reprogramming events declined over time; at the 5-
onabotulinumtoxinA treatment and SNS test phase was year point, rates were 0.24 and 0.95 respectively.
23 months. At one year post-implant, 11 of 14 patients Explant rates for OAB-wet were 10.9% (32/294) and
(79%) reported satisfaction with treatment. for OAB-dry 8.7% (10/115). In comparison, IC
patients had an explant rate of 57.9%.
In contrast to PTNS studies (see discussion under
Guideline Statement 18), SNS studies reported frequent The Panel interpreted these data to indicate that in
adverse events, including pain at the stimulator site carefully selected patients, SNS is an appropriate
(3.3 to 19.8% of patients), pain at the lead site (4.5 to therapy that can have durable treatment effects but in
19.1% of patients), lead migration (1.1 2.2 to 8.6% of the context of frequent and moderately severe adverse
patients), infection/irritation (2.2 to 14.30% of events, including the need for additional surgeries. The
patients), electric shock (5.5 to 10.2 7.9% of patients) Panel notes that patients should be counseled that the
and need for surgical revision (6.25 to 39.5% of device requires periodic replacement in a planned
patients). In most studies, the need for surgical surgical procedure and that the length of time between
revision occurred in greater than 30% of patients. replacements depends on device settings. Patients also
There is some evidence that newer, less invasive must be willing to comply with the treatment protocol
surgical procedures and tined devices may be because treatment effects typically are only maintained
associated with fewer adverse events.170 Leong (2011) as long as the therapy is maintained and have the
reported that although 90% of patients reported cognitive capacity to use the remote control to optimize
satisfaction with SNS, 56% reported adverse events, device function. In addition, patients must accept that
particularly pain at the stimulator site and when the the use of diagnostic MRIs is contraindicated in
stimulator was turned on and daily life limitations, such individuals with the device implanted. Given the
as difficulty passing through airport metal detectors and negative effects on quality of life associated with severe
inability to undergo magnetic resonance imaging incontinence and frequency, the Panel judged that
(MRI).165 benefits of SNS in the appropriate patient outweighed
the risks/burdens and notes that patients should be
Additional useful information is provided by Lai and carefully counseled regarding the risks/burdens.
Grewal (2013) who investigated the bacterial Evidence strength is Grade C because of the
colonization rate of the connector and lead during predominance of observational designs, the small
staged testing.269 During the stage II procedure, sample sizes, the limited number of unique patient
aerobic and anaerobic cultures were obtained by groups (i.e., there are multiple reports on the same
swabbing the connector pocket, the connector, and the patient groups followed over time) and limited
permanent lead itself. Of 38 patients, 9 (24%) had a information regarding the protocols used by patients to
positive culture at the connector or lead site. Of the 9 maintain symptom control.
patients with a positive culture, 3 (33.3%)
subsequently developed device infection that required Guideline Statement 20.
explant compared to 3% of patients who did not have
Practitioners and patients should persist with
colonization but who subsequently developed an
new treatments for an adequate trial in order to
infection. Longer percutaneous testing was associated
determine whether the therapy is efficacious and
with a greater colonization rate. Of 10 patients who

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Guideline Statements

tolerable. Combination therapeutic approaches treatments (other than surgery), the magnitude of
should be assembled methodically, with the placebo effects, and the principle that symptom
addition of new therapies occurring only when reductions are proportional to baseline symptom level
the relative efficacy of the preceding therapy is for UUI episodes, incontinence episodes, and frequency.
known. Therapies that do not demonstrate
efficacy after an adequate trial should be ceased. Additional Treatments
Expert Opinion
Guideline Statement 21.
Discussion. The Panel members note that they
Indwelling catheters (including transurethral,
regularly encounter patients who present for second-
suprapubic, etc.) are not recommended as a
line (pharmacologic management) or third-line
management strategy for OAB because of the
treatments (onabotulinumtoxinA, PTNS, or SNS) who
adverse risk/benefit balance except as a last
have never undergone a comprehensive evaluation
resort in selected patients. Expert Opinion
(i.e., completion of a voiding diary to ensure the OAB
diagnosis is correct) or who have never had a trial of
Discussion. In situations where the medical
behavioral therapy or who have had an inadequate trial
management of burdensome OAB, as outlined above, is
of behavioral therapy. Similarly, it is not uncommon
not feasible, effective nor recommended, as in the
for patients to present for non-medical treatments who
patient with severe cognitive deficits or mobility issues,
have not had an adequate trial of medications. On the
then other management options may need to be
other hand, the Panel also encounters patients who are
considered. Management with diapering and absorbent
being treated with multiple simultaneous therapies
garments is always preferred to indwelling
without clear evidence of the efficacy of the individual
catheterization because of the high risk of indwelling
therapies or their combination. The Panel encourages
catheter-associated UTIs, urethral erosion/destruction
practitioners and patients to persist with new
and urolithiasis. Intermittent catheterization may be an
treatments (4 to 8 weeks for medications and 8 to 12
option when concomitant incomplete bladder emptying
weeks for behavioral therapies) for a sufficient duration
is present leading to overflow incontinence; however,
to achieve clarity regarding efficacy and adverse events
this approach generally requires either patient
for a particular therapy before abandoning the therapy
willingness and ability or significant caregiver support.
prematurely or before adding a second therapy. If a
As a last resort, an indwelling catheter may be
comprehensive evaluation has demonstrated that the
considered when urinary incontinence has resulted in
patient has signs and symptoms consistent with the
the development and progression of decubiti, during
OAB diagnosis and a particular therapy is not
the management of those decubiti, or rarely, where
efficacious after a reasonable trial, then an alternative
urinary incontinence is the predominant disability
therapy should be tried. Combination therapeutic
affecting activities of daily living and therefore may
approaches should be assembled methodically,
result in institutionalization.
beginning with the establishment of confidence in the
partial efficacy of one therapy, continuing with an Guideline Statement 22.
adequate trial of any additional therapies one at a time
until the patient experiences adequate symptom control In rare cases, augmentation cystoplasty or
in the context of tolerable adverse events. If a patient urinary diversion for severe, refractory,
does not achieve adequate symptom control with this complicated OAB patients may be considered.
approach, then referral to a specialist should be Expert Opinion
considered.
Discussion. In general, surgery is not recommended
Behavioral, Pharmacologic, and Procedural for OAB patients except in extremely rare cases. The
Treatments in Context vast majority of case series that document the effects
of augmentation cystoplasty and diversion focus on
The following plots (Figure 3) are presented to neurogenic patients. Little is known regarding the
demonstrate the heterogeneity of OAB patients in impact of these procedures on non-neurogenic OAB
terms of baseline symptomatology, the different ranges patients and, particularly, on their quality of life. There
of patients typically treated with the available are substantial risks to these procedures, however,

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AUA/SUFU Guideline Overactive Bladder

Guideline Statements
Figure 3: Heterogeneity of OAB Patients

including the likely need for long-term intermittent self-

catheterization and the risk of malignancy.271 In the
Panel’s judgment, therefore, a surgical approach to
OAB treatment is appropriate only in the extremely rare
patient.

Follow-Up

Guideline Statement 23.

The clinician should offer follow up with the

patient to assess compliance, efficacy, side
effects and possible alternative treatments.
Expert Opinion

Discussion. The purpose of follow-up is to assess

compliance with treatment protocols, query patients
regarding symptom improvements and any adverse
events and present information about possible
alternative treatments to patients who have insufficient
symptom improvement and/or intolerable adverse
events. There are many ways to measure symptom
changes, including voiding diaries with or without
frequency-volume charts and patient-rated global
response scales for urgency, urgency incontinence,
incontinence, frequency and nocturia. In addition,

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AUA/SUFU Guideline Overactive Bladder

Future Directions

validated OAB-specific instruments may be used to have undergone surgical treatments (e.g.,
assess the impact of OAB symptoms on quality of life. augmentation cystoplasty with or without sling,
Ideally, clinicians should obtain baseline measures supravesical diversion) or permanent or semi-
using the same instruments in order to chart progress. permanent catheter placements also should be followed
Patients should be encouraged to persist with a regularly for symptom level, QoL and any
particular treatment for four to eight weeks; this time complications. Patients who are using incontinence
period will identify the majority of responders.61 pads, regardless of whether or how they are being
treated, should be followed for appropriate skin care
Clinicians and any clinical personnel engaged in follow- and skin integrity.
up should be aware that the various treatment options
for OAB have different requirements for efficacy and Section 7: Research Needs and Future Directions
different adverse event probabilities and severities. For
example, the efficacy of some treatments (e.g., Better Stratification of OAB. OAB, because it is a
behavioral therapies, neuromodulation) depends greatly symptom complex, is primarily a diagnosis of exclusion.
on treatment compliance, and the efficacy must be Treatments are aimed at relieving symptoms and not
balanced against possible adverse events. For other necessarily at reversing pathophysiologic abnormalities.
treatments, such as the use of anti-muscarinics, Understanding the pathophysiology and the risk factors
adverse events are common but vary in severity across for development of OAB is needed both to treat the
patients. Patients should be informed about and syndrome as well as to prevent it. Future research will
subsequently queried regarding dry mouth and its need to address the entire spectrum of research
severity (i.e., sufficient to impair alimentation), endeavors including epidemiology, QoL measurements,
constipation, fecal retention and any possible central treatment modalities and basic bladder physiology
nervous system (CNS) effects. Queries of the patient including sensory and motor signaling. Within the field
and caregiver regarding CNS effects are particularly of OAB, research sometimes is dichotomized between
important in elderly or frail patients; clinical experience OAB/lower urinary tract symptoms or LUTS (e.g., OAB-
suggests that CNS effects can be severe enough to dry) versus OAB/urgency incontinence (OAB-wet).
cause loss of independent living skills in some patients. However, this type of compartmentalization highlights
Non-responders to anti-muscarinics should be tried on our lack of understanding of OAB. In other words, are
at least one other anti-muscarinic or mirabegron and/or OAB-dry and OAB-wet pathophysiologically related? Is
dose modification attempted to determine if a better OAB-dry a milder manifestation of the OAB condition
balance between efficacy and adverse events occurs. If which progresses to OAB-wet over time? Or are OAB-
adverse events are severe enough to compromise dry and OAB-wet two different conditions with different
patient quality of life, then strategies to manage pathophysiologic mechanisms? How can we better
specific adverse events, such as ameliorating objectively measure bladder symptoms? In addition,
constipation with appropriate bowel management, particularly in females, stress urinary incontinence
should be implemented before abandoning anti- (SUI) symptoms may exist concomitantly with OAB-
muscarinic treatment. symptoms (dry or wet). Further, isolated nocturia is a
separate symptom entity, requiring different evaluation
For peripheral tibial nerve stimulation and sacral and management strategies. This overlap in bladder
neuromodulation, pre- and post-therapy measures are symptoms is captured in the Venn diagram below with
essential to assess efficacy. The before-and-after their potential to be concomitantly present. This Venn
evaluation should include baseline assessment with a diagram will appear different based on the gender and
voiding diary and assessment of urgency as well as a age of the population depicted; the diagram included
global response assessment. Adverse events such as here is intended to provide a point of reference for
pain and collateral stimulation should be assessed, and discussion. Therefore, the phenotype of bladder
sacral neuromodulation wound complications should be symptoms should be carefully considered and declared
evaluated. in all research to clarify the particular patient group
being studied.
Patients treated with intradetrusor onabotulinumtoxinA
should be followed for the possibility of increased PVRs Epidemiology. Studies assessing how OAB develops
and the need for self-catheterization. Patients who and its natural history and progression are required.

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Future Directions

The timing and circumstances around which OAB findings.

develops and associated risk factors are not yet well-
understood. While not specifically targeting Clinical studies should use validated standardized
epidemiology of OAB, there are large community-based measures to report subjective outcomes. Objective
studies that assess prevalence of lower urinary tract outcomes should include frequency, nocturia, urgency,
symptoms and urinary incontinence.272, 273 By incontinence episode frequency and reporting of the
longitudinally studying these community cohorts, these variance for each of these measures. Furthermore, the
investigators have developed a new hypothesis that Guideline Panel’s meta-analytic efforts were hampered
lower urinary tract symptoms are likely related to other by lack of consistent reporting of variance information
systemic diseases/conditions.274, 275 Continuation of (e.g., standard deviations, standard errors of the
these types of studies could lead to potential preventive mean) for baseline and post-treatment measurements.
interventions for OAB symptoms and/or utilization of
The effect of treatment of OAB on the elderly, the very
treatments that target the associated systemic
frail and those with pre-existing cognitive deficiencies
conditions rather than the bladder. Epidemiologic
needs further research. These include measures of
studies provide a better cross sectional estimation of
cognitive side effects from anti-muscarinic treatments.
the overall population impact of OAB-type symptoms.276
Basic Science / Translational Research. The
Clinical Research. As discussed previously, several
finding of a biomarker for OAB would advance the
validated OAB-symptom and OAB-symptom bother
pathophysiologic understanding of OAB. Investigated
tools have been developed. However, objective
biomarkers which have been published include nerve
measures of the “cornerstone” OAB-symptom of
growth factor,281 corticotrophin releasing factor,282
urgency277 remains poorly assessed. As defined by the
prostaglandins283 and inflammatory factors such as C -
International Continence Society,27 “urgency is the
reactive protein.284 Another approach to find potential
complaint of a sudden compelling desire to pass urine
relevant biomarkers is to utilize high throughput DNA
which is difficult to defer.” Investigators have tested
array profiles, using subtractive techniques to identify
urgency questionnaires to assess for validity and
uniquely expressed genes in OAB (as compared to
reliability;278-280 however, no single measure is used
controls).285 However, this approach is non-targeted
consistently across trials, making it difficult to compare
and may result in selection of many spurious, non-OAB
Figure 4: OAB Patient Groups specific candidate biomarkers.

Functional MRI (fMRI) has provided an imaging tool to

ascertain the roles of the central nervous system
(brain/cerebrum) in mediating bladder symptoms and
whether there are visible abnormalities in subjects with
OAB-symptoms. Different investigative groups have
reported findings of alterations in brain processing of
bladder sensory signals in OAB subjects.286, 287

Sensory (afferent) signaling from the bladder and

urethra has been studied with various methodologies.
The ideal sensory testing for the lower urinary tract
that will have clinical impact in evaluation and
management of OAB is not known. Use of current
perception thresholds (CPT) electrophysiologic testing
as a research tool has been described both in
asymptomatic and OAB individuals.288-290 A recent
review has also highlighted the potential interaction of
the bladder urothelium, suburothelium and interstitial
cells with the sensory afferent pathways.291 The
urothelium has been proposed to be a “sensor-
transducer” cellular compartment with urothelial cells

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AUA/SUFU Guideline Overactive Bladder

Future Directions

able to release and respond to neurotransmitters, thus

able to communicate with the afferent nerve endings
that terminate within the urothelium.292 The bladder
suburothelium and detrusor muscle compartments are
purported to contain “pacemaker-like” cells, similar to
interstitial cells of Cajal found in the gut, which can
modulate bladder contractility, rhythmicity and/or
overactivity.293 A more complete understanding of
sensory mechanisms could lead to novel OAB therapies.

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 40

AUA/SUFU Guideline Overactive Bladder

References

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AUA/SUFU Guideline Overactive Bladder

Panel, Consultants, Staff and COI

Overactive Bladder Panel, Consultants and Staff Conflict of Interest Disclosures

Panel Members All panel members completed COI disclosures.

Relationships that have expired (more than one year
E. Ann Gormley, M.D. old) since the panel’s initial meeting, are listed. Those
Dartmouth-Hitchcock Med. Ctr. marked with (C) indicate that compensation was
Lebanon, NH received; relationships designated by (U) indicate no
compensation was received.
Deborah J. Lightner, M.D.
Mayo Clinic Consultant/Advisor: Toby C. Chai, Allergan (C),
Rochester, MN Medtronic (C), Ion Channel, Inc. (C), Astellas (C)
(expired); Harriette M. Scarpero, American Medical
Kathryn L. Burgio, Ph.D. Systems (AMS) (C), Allergan (C); J. Quentin
University of Alabama at Birmingham Clemens, Medtronic , (C), Amphora Medical (C),
Birmingham, AL United Biosource Corporation (C)(expired), Pfizer (C)
(expired), Afferent Pharmaceuticals, Inc. (C)(expired);
Toby C. Chai, M.D. Daniel J. Culkin, American Medical Systems (AMS)
University of Maryland School of Medicine (C); Sandip P. Vasavada, American Medical Systems
Baltimore, MD (C), Allergen (C); Boston Scientific (C)(expired);
Kathryn L. Burgio, Johnson & Johnson (C), Astellas
J. Quentin Clemens, M.D. (C), Pfizer (C)
University of Michigan
Ann Arbor, MI Investigator: J. Quentin Clemens, Pfizer (C)
(expired); Daniel J. Culkin, Watson Pharmaceuticals
Daniel J. Culkin, M.D. (U)(expired)
University of Oklahoma HSC
Oklahoma City, OK Meeting Participant or Lecturer: Harriette M.
Scarpero, Allergan (C), Pfizer (C)(expired), Astellas
Anurag Kumar Das, M.D. US, (C)(expired), Lilly (C)(expired); Daniel J. Culkin,
Beth Israel Deaconess Medical Center American Medical Systems (AMS) (C); Allergan, Pfizer
Boston, MA (C), Allergen (C); Kathryn L. Burgio, Pfizer (C)

Harris Emilio Foster, Jr. M.D. Scientific Study or Trial: Elizabeth Ann Gormley,
Yale University School of Medicine National Institute of Health - NIDDK (C); Toby C. Chai,
New Haven, CT Allergan (C), National Institutes of Health (U);
Harriette M. Scarpero, Pfizer (U), Daniel J. Culkin,
Harriette Miles Scarpero, M.D. Medtronic (U), Taris Pharmaceuticals (C); Sandip P.
St. Thomas Hospital Vasavada, allergen (C); Kathryn L. Burgio, Pfizer (C)
Nashville, TN
Investment Interest: Deborah J. Lightner, Amgen
Christopher D. Tessier, M.D. (C)(expired), Vertex Pharmaceuticals (C)(expired),
Manchester Urology Associates Celgene (C)(expired); J. Quentin Clemens, Merck (U);
Manchester, NH Anurag Kumar Das, Amgen (U), Novartis (U), Sanofi-
Aventis (U), Astellas (U), Johnson and Johnson (U),
Sandip Prasan Vasavada, M.D. Novo Nordisk (U); Sandip P. Vasavada, NDI Medical
Cleveland Clinic Foundation LLC (C); Christopher D. Tessier, United Medical
Cleveland, OH Systems (C), Healthtronics (C)

Consultants Other: Toby C. Chai, Taris Biomedical (C)

Martha M. Faraday, Ph.D.
Wayne Brandes, D.O., M.P.H., [Link]

Staff
Heddy Hubbard, Ph.D., MPH, RN, FAAN
Michael Folmer
Abid Khan, MHS
Erin Kirkby, M.S.
Ashley Keys

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AUA/SUFU Guideline Overactive Bladder

Peer Reviewers and Disclaimer

Peer Reviewers available data, for optimal clinical practices in the

We are grateful to the persons listed below who diagnosis and treatment of overactive bladder.
contributed to the Overactive Bladder Guideline by
providing comments during the peer review process. Funding of the committee was provided by the AUA and
Their reviews do not necessarily imply endorsement of the Society for Urodynamics, Female Pelvic Medicine &
the Guideline. Urogenital Reconstruction. Committee members
received no remuneration for their work. Each member
Cindy L. Amundsen, MD of the committee provides an ongoing conflict of
John M. Barry, M.D. interest disclosure to the AUA.
William W. Bohnert, M.D.
Michael B. Chancellor, M.D. While these guidelines do not necessarily establish the
Daniel J. Culkin, M.D. standard of care, AUA seeks to recommend and to
Roger R. Dmochowski, M.D. encourage compliance by practitioners with current best
Christopher Girasole practices related to the condition being treated. As
Howard B. Goldman, M.D. medical knowledge expands and technology advances,
Alexander Gomelsky, M.D. the guidelines will change. Today, these evidence-
David F. Green, M.D., FACS based guideline statements represent not absolute
Philip M. Hanno, M.D. mandates but provisional proposals for treatment under
Damara Lee Kaplan, M.D. the specific conditions described in each document. For
Jeffrey E. Kaufman, MD, FACS all these reasons, the guidelines do not pre-empt
Kathleen C. Kobashi, M.D. physician judgment in individual cases.
Cheryl A. LeCroy, NP
Gary E. Lemack, M.D. Treating physicians must take into account variations in
Kevin R. Loughlin, M.D. resources, and patient tolerances, needs, and
John H. Lynch, M.D. preferences. Conformance with any clinical guideline
Elizabeth R. Mueller, MD does not guarantee a successful outcome. The
Victor W. Nitti, M.D. guideline text may include information or
Anne Pelletier Cameron, MD recommendations about certain drug uses (‘off label’)
Kevin Pranikoff, M.D. that are not approved by the Food and Drug
Hassan Razvi, M.D. Administration (FDA), or about medications or
Holly Richter, M.D., PhD substances not subject to the FDA approval process.
Leslie M. Rickey, M.D. AUA urges strict compliance with all government
Eric S. Rovner , M.D. regulations and protocols for prescription and use of
Phillip Smith, M.D. these substances. The physician is encouraged to
Pramod C. Sogani, M.D. carefully follow all available prescribing information
William D. Steers, M.D. about indications, contraindications, precautions and
Veronica Triaca, M.D. warnings. These guidelines are not intended to
Datta G. Wagel, M.D. provide legal advice about use and misuse of these
Jeffrey P. Weiss, MD substances.
Blayne K. Welk, M.D.
Tracey S. Wilson, M.D. Although guidelines are intended to encourage best
J. Christian Winters, M.D. practices and potentially encompass available
J. Stuart Wolf, Jr., M.D. technologies with sufficient data as of close of the
Chris E. Wolter, MD literature review, they are necessarily time-limited.
Leslie S. Wooldridge, CNP Guidelines cannot include evaluation of all data on
Claire C. Yang, MD emerging technologies or management, including those
that are FDA-approved, which may immediately come
Disclaimer to represent accepted clinical practices.
This document was written by the Overactive Bladder For this reason, the AUA does not regard technologies
Guidelines Panel of the American Urological Association or management which are too new to be addressed by
Education and Research, Inc., which was created in these guidelines as necessarily experimental or
2009. The Practice Guidelines Committee (PGC) of the investigational.
AUA selected the panel chair. Panel members were
selected by the chair. Membership of the panel included
urologists and other clinicians with specific expertise on
this disorder. The mission of the committee was to
develop recommendations that are analysis-based or
consensus-based, depending on Panel processes and

Copyright © 2014 American Urological Association Education and Research, Inc.®