American Urological Association - Diagnosis and Treatment of Non-Neurogenic Overactive Bladder (OAB) in Adults: AUA/SUFU Guideline

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Home Guidelines Clinical Guidelines Overactive Bladder (OAB) (AUA/SUFU Guideline: 2012; Amended 2014)

Diagnosis and Treatment of Non-Neurogenic Overactive Bladder (OAB) in Adults: AUA/SUFU Guideline

AUA/SUFU Guideline: Published 2012; Amended 2014

Unabridged version of this Guideline [pdf]
Algorithm associated with this Guideline [pdf]

Panel Members

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 Miles Scarpero, Christopher D. Tessier, Sandip Prasan Vasavad

Executive Summary

Purpose

The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of non-neurogenic overactive bladder (OAB).

Methods

The primary source of evidence for the original version of this guideline was the systematic review and data extraction conducted as part of the Agency for Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment 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 cause of the patient's symptoms; the minimum requirements for this process are a careful history, physical exam, and urinalysis. Clinical Principle

2. In some patients, additional procedures and measures may be necessary to validate an OAB diagnosis, exclude other disorders and fully inform the treatment plan. At the clinician's discretion, a urine culture and/or post-void residual assessment may be performed and information from bladder diaries and/or symptom questionnaires may be obtained. Clinical Principle

3. Urodynamics, cystoscopy and diagnostic renal and bladder ultrasound should not be used in the initial workup of the uncomplicated patient. Clinical Principle

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

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-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

Purpose

This guideline's purpose is to provide direction to clinicians and patients regarding how to recognize non-neurogenic overactive bladder (OAB), conduct a valid diagnostic process and approach treatment with the goals of maximizing symptom control and patient quality of life while minimizing adverse events and patient burden. The strategies and approaches recommended in this document were derived from evidence-based and consensus-based processes. There is a continually expanding literature on OAB; the Panel notes that this document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient. As the science relevant to OAB evolves and improves, the strategies presented here will require amendment to remain consistent with the highest standards of clinical care. This document was created to serve as a guide for all types of providers who evaluate and treat OAB patients, including those in general practice as well as those who specialize in various branches of medicine.

Methodology

The primary source of evidence for the first version of this guideline was the systematic review and data extraction conducted as part of the Agency for Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment Number 187 titled Treatment of Overactive Bladder in Women (2009).1 That report, prepared by the Vanderbilt University Evidence-Based Practice Center (EPC), searched PubMed, MEDLINE, EMBASE and CINAHL for English-language studies published from January 1966 to October 2008 relevant to OAB and excluded non-relevant studies, studies with fewer than 50 participants and studies with fewer than 75% women. AUA conducted an additional literature search to capture articles published between October 2008 and December 2011. In addition, because the Panel wished to consider data for male as well as female patients, studies excluded by the AHRQ report because there were fewer than 75% women participants were extracted and added to the database. Studies that focused primarily on nocturia were also added to the database. Given that the AHRQ report included limited information regarding use of neuromodulation therapies, including sacral neuromodulation (SNS) and peripheral tibial nerve stimulation (PTNS) (also known as posterior tibial nerve stimulation) and limited information regarding the use of intravesical onabotulinumtoxinA to treat non-neurogenic OAB patients, additional searches were performed to capture this literature and relevant data were added to the database. 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 articles were added to the database, and AUA's qualitative and quantitative analyses were updated as appropriate.

Data from studies published after the literature search cut-off will be incorporated into the next version of this guideline. Preclinical studies (e.g., animal models), pediatric studies, commentary and editorials were eliminated. Review article references were checked to ensure inclusion of all possibly relevant studies. Multiple reports on the same patient group were carefully examined to ensure inclusion of only nonredundant information.

OAB Diagnosis. The review revealed insufficient publications to address OAB diagnosis from an evidence basis; the diagnosis portions of the algorithm (see Figure 1), therefore, are provided as Clinical Principles or as Expert Opinion with consensus achieved using a modified Delphi technique if differences of opinion emerged.2 A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other expert clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge and judgment for which there is no evidence.

OAB Treatment. With regard to treatment, a total of 151 articles from the original search processes met the inclusion criteria; an additional 72 relevant articles were retrieved as part of the update literature review process and also have been incorporated. The Panel judged that these were a sufficient evidence base from which to construct the majority of the treatment portion of the algorithm. Data on study type (e.g., randomized controlled trial, controlled clinical trial, observational study), treatment parameters (e.g., dose, administration protocols, follow-up durations), patient characteristics (i.e., age, presence of specific symptoms such as urgency, urgency incontinence and/or frequency, detrusor overactivity documented by urodynamics), adverse events, and primary outcomes (as defined by study authors) were extracted. The primary outcomes for most studies were reductions in frequency, urgency incontinence, incontinence and urgency.

Quality of Individual Studies and Determination of Evidence Strength. The quality of individual studies was assessed by the EPC using accepted criteria to determine the quality of internal and external validity. The criteria and rating scheme are described in detail in the published report. The same system was used to assess the quality of additional included studies.

Table 1: AUA Nomenclature
Linking Statement Type to Level of Certainty and Evidence Strength [Updated Version]
Standard: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade A (high quality; high certainty) or B (moderate quality; moderate certainty) evidence
Recommendation: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade C (low quality; low certainty) evidence
Option: Non-directive statement that leaves the decision regarding an action up to the individual clinician and patient because the balance between benefits and risks/burdens appears equal or appears uncertain based on Grade A (high quality; high certainty), B (moderate quality; moderate certainty), or C (low quality; low certainty) evidence
Clinical Principle: a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature
Expert Opinion: a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there is no evidence

The categorization of evidence strength (ES) is conceptually distinct from the quality of individual studies. Evidence strength refers to the body of evidence available for a particular question and includes consideration of study design, individual study quality, consistency of findings across studies, adequacy of sample sizes and generalizability of samples, settings and treatments for the purposes of the guideline. AUA categorizes evidence strength as Grade A (well-conducted RCTs or exceptionally strong observational studies), Grade B (RCTs with some weaknesses of procedure or generalizability or generally strong observational studies) or Grade C (observational studies that are inconsistent, have small sample sizes or have other problems that potentially confound interpretation of data).

AUA Nomenclature: Linking Statement Type to Evidence Strength. The AUA nomenclature system explicitly links statement type to body of evidence strength and the Panel's judgment regarding the balance between benefits and risks/burdens.3 Standards are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken based on Grade A (high level of certainty) or Grade B (moderate level of certainty) evidence. Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken based on Grade C (low level of certainty) evidence. Options are non-directive statements that leave the decision to take an action up to the individual clinician and patient because the balance between benefits and risks/burdens appears relatively equal or unclear; Options may be supported by Grade A (high certainty), B (moderate certainty) or C (low certainty) evidence. Options generally reflect the Panel's judgment that a particular decision is best made by the clinician who knows the patient with full consideration of the patient's prior treatment history, current quality of life, preferences and values.

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 limitations included the use of different inclusion criteria across studies assessing the same treatment, poorly-defined patient groups or use of patient groups with limited generalizability to the typical clinical setting in which OAB patients are seen, lack of consistency in outcome measures and limited outcome measure and adverse event reporting. With regard to measures, although most studies reported urinary frequency and urinary incontinence, many studies did not report other key measures such as urgency, and only a handful reported nocturia data. With regard to adverse events, most pharmacologic studies reported rates of dry mouth and constipation, but few reported on other clinically-relevant issues such as cardiac or cognitive adverse events. The original completed evidence report and the updated literature review evidence report may be requested from AUA.

The Overactive Bladder Panel was created in 2009 by the American Urological Association Education and Research, Inc. (AUA). The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chair and Vice Chair who in turn appointed the additional panel members with specific expertise in this area. The AUA conducted a thorough peer review process of the original document. The draft guidelines document was distributed to 78 peer reviewers, of whom 31 provided comments. The panel reviewed and discussed all submitted comments and revised the draft as needed. Once finalized, the guideline was submitted for approval to the PGC. Then it was submitted to the AUA Board of Directors (BOD) for final approval. Funding of the panel was provided by the AUA and the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU), although panel members received no remuneration for their work. AUA's amendment process provides for the amendment of existing evidence-based guideline statements and/or the creation of new evidence-based guideline statements in response to the publication of a sufficient volume of new evidence. The process also provides for the amendment or addition of Clinical Principle and Expert Opinion statements based on consensus among panel members that elements of current practice have shifted such that a new or revised Clinical Principle or Expert Opinion statement is needed. Evidence-based guideline amendments require the agreement of a methodologist and panel members that new evidence is sufficient to change or add evidence-based statements. All guideline amendments require approval of the AUA Practice Guidelines Committee (PGC) and BOD.

Background

Definition. Overactive bladder (OAB) is a clinical diagnosis characterized by the presence of bothersome urinary symptoms. Most studies of OAB, including this guideline, exclude individuals with symptoms related to neurologic conditions. The International Continence Society (ICS) defines OAB as the presence of "urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of UTI or other obvious pathology."4 Therefore, OAB symptoms consist of four components: urgency, frequency, nocturia and urgency incontinence. OAB studies have used varying combinations of these symptoms to identify patients for study inclusion and to define treatment response. These methodologic differences across studies make it a challenge to interpret the OAB literature related to epidemiology and treatment.

Urgency is defined by the ICS as the "complaint of a sudden, compelling desire to pass urine which is difficult to defer."4 Urgency is considered the hallmark symptom of OAB, but it has proven difficult to precisely define or to characterize for research or clinical purposes. Therefore, many studies of OAB treatments have relied upon other measures (e.g., number of voids, number of incontinence episodes) to measure treatment response.

Urinary frequency can be reliably measured with a voiding diary. Traditionally, up to seven micturition episodes during waking hours has been considered normal,5 but this number is highly variable based upon hours of sleep, fluid intake, comorbid medical conditions and other factors.

Nocturia is the complaint of interruption of sleep one or more times because of the need to void.4 In one study, three or more episodes of nocturia constitutes moderate or major bother.6 Like daytime frequency, nocturia is a multifactorial symptom which is often due to factors unrelated to OAB (e.g., excessive nighttime urine production, sleep apnea).

Urgency urinary incontinence is defined as the involuntary leakage of urine, associated with a sudden compelling desire to void. Incontinence episodes can be measured reliably with a diary, and the quantity of urine leakage can be measured with pad tests. However, in patients with mixed urinary incontinence (both stress and urgency incontinence), it can be difficult to distinguish between incontinence subtypes. Therefore, it is common for OAB treatment trials to utilize total incontinence episodes as an outcome measure.

Epidemiology. In population-based studies, OAB prevalence rates range from 7% to 27% in men, and 9% to 43% in women.7-14 No clear differences exist between studies conducted in North America vs. other populations. Some studies report higher prevalence rates in women than men,7-10 while others found similar rates across genders.11-14 However, urgency urinary incontinence is consistently more common in women than in men. OAB symptom prevalence and severity tend to increase with age.11-12, 15 A proportion of OAB cases (37-39%) remit during a given year, but the majority of patients have symptoms for years.15,16 To date, no population-based studies have directly examined epidemiologic differences across racial/ethnic groups.

Patient-Reported Outcomes (PROs) and OAB. Since OAB is a symptom-based diagnosis, the quality of life (QOL) impact of the symptoms is a critical aspect of the condition. The degree of bother caused by OAB symptoms directly affects OAB care-seeking, treatment intensity and satisfaction with treatment. Therefore, assessment of patient-reported outcomes (PROs) can be a critical component of OAB management. Numerous questionnaire instruments have been developed to assess symptoms, degree of bother and health-related QOL in patients with OAB and urinary incontinence.17 This lack of standardization has often limited the comparability and generalizability of PROs across research studies. To address this, the International Consultation on Incontinence has developed a series of standardized modular questionnaires for pelvic conditions, including OAB.18 The Panel encourages the development of such standardized PRO tools which can be used in OAB research and clinical practice.

Impact on Psychosocial Functioning and Quality of Life (QoL). The Panel fully recognizes that OAB constitutes a significant burden for patients. These burdens include the time and effort required to manage symptoms during the course of daily life as well as the resources required to obtain treatments that may be costly and may present logistical challenges (e.g., therapies that require frequent visits to a physician's office). The negative impact of OAB symptoms on psychosocial functioning and quality of life also has been well-documented.19-22 Carrying out the activities of daily life and engaging in social and occupational activities can be profoundly affected by lack of bladder control and incontinence. Urinary incontinence in particular may have severe psychological and social consequences, resulting in restricted activities and unwillingness to be exposed to environments where access to a bathroom may be difficult. Patients also report negative impact on sexual function and marital satisfaction 23 and OAB symptoms have been linked to depressive illness.24, 25 This negative impact also is evident among older adults (e.g., ≥ 65 years), resulting in significant impairments in QoL, including high rates of anxiety and depression, with the majority of patients reporting they have not sought treatment.26

Successful treatment of OAB symptoms with behavioral approaches, medications, neuromodulation therapies, and onabotulinumtoxinA, balanced against adverse events, costs and ultimately patient compliance, all have been reported to improve patient quality of life (see Discussion sections under each treatment type).

Patient Presentation

Symptoms. When symptoms of urinary frequency (both daytime and night) and urgency, with or without urgency incontinence, are self-reported as bothersome the patient may be diagnosed with overactive bladder (OAB).27 Additionally, a caregiver or partner may perceive these symptoms as bothersome and lead the patient to seek care. It is common for patients to have suffered with their symptoms for an extended time before seeking medical advice.

Differentiation.  OAB symptoms (frequency, urgency and urgency incontinence) may occur only at night, causing a single symptom of nocturia. The differential of nocturia includes nocturnal polyuria (the production of greater than 20 to 33% of total 24 hour urine output during the period of sleep, which is age-dependent with 20% for younger individuals and 33% for elderly individuals),28 low nocturnal bladder capacity or both. In nocturnal polyuria, nocturnal voids are frequently normal or large volume as opposed to the small volume voids commonly observed in nocturia associated with OAB. Sleep disturbances, vascular and/or cardiac disease and other medical conditions are often associated with nocturnal polyuria. As such, it is often age-dependent, increasing in prevalence with aging and with poorer general health.

OAB also must be distinguished from other conditions such as polydipsia. In OAB, urinary frequency is associated with many small volume voids. Frequency that is the result of polydipsia and resulting polyuria may mimic OAB; the two can only be distinguished with the use of frequency-volume charts. In polydipsia, urinary frequency occurs with normal or large volume voids and the intake is volume matched. In this case, the frequency is appropriate because of the intake volume and the patient does not have OAB. Frequency due to polydipsia is physiologically self-induced OAB and should be managed with education, with consideration of fluid management. Similarly, diabetes insipidus (DI) also is associated with frequent, large volume voids and should be distinguished from OAB.

The clinical presentation of interstitial cystitis/ bladder pain syndrome shares the symptoms of urinary frequency and urgency, with or without urgency incontinence; however, bladder and/or pelvic pain, including dyspareunia, is a crucial component of its presentation in contradistinction to OAB. Other conditions also can contribute to OAB symptoms and should be assessed. For example, in the menopausal female patient, atrophic vaginitis can be a contributing factor to incontinence symptoms. There is some evidence for symptom improvement with the use of vaginal (but not systemic) estrogen.29

Diagnosis

The Diagnostic Approach. Insufficient literature was identified to constitute an evidence base for diagnosis of OAB in clinical practice. For this reason, the section titled Diagnosis is based on Clinical Principles or Expert Opinion with consensus achieved using a modified Delphi technique when differences of opinion emerged. This section is intended to provide clinicians and patients with a framework for determining whether a diagnosis of OAB is appropriate; it is not intended to replace the judgment and experience of the individual clinician faced with a particular patient.

Guideline Statement 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 cause of the patient's symptoms; the minimum requirements for this process are a careful history, physical exam and urinalysis. Clinical Principle

Discussion


Guideline Statement 2

In some patients, additional procedures and measures may be necessary to validate an OAB diagnosis, exclude other disorders and fully inform the treatment plan. At the clinician's discretion, a urine culture and/or post-void residual assessment may be performed and information from bladder diaries and/or symptom questionnaires may be obtained. Clinical Principle

Discussion


Guideline Statement 3

Urodynamics, cystoscopy and diagnostic renal and bladder ultrasound should not be used in the initial workup of the uncomplicated patient. Clinical Principle

Discussion


Guideline Statement 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

Discussion


Guideline Statement 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.

Discussion


Treatments

Issues to Consider. It is important to recognize that OAB is a symptom complex that may compromise quality of life (QoL) but generally does not affect survival. Given this context, in pursuing a treatment plan the clinician should carefully weigh the potential benefit to the patient of a particular treatment against that treatment's risk for adverse events, the severity of adverse events and the reversibility of adverse events. The guideline statements in this section are intended to provide a framework to assist the clinician in counseling patients and in developing an individualized treatment plan that optimizes quality of life.

In developing the treatment portion of the algorithm, the balance between benefits and risks/burdens (i.e., adverse events) was considered. The Panel conceptualized risks/burdens in terms of the invasiveness of the treatment, the duration and severity of potential adverse events and the reversibility of potential adverse events. Treatment alternatives were then divided into first-, second-, third-, fourth- and fifth-line groups. This hierarchy was derived by balancing the potential benefits to the patient with the invasiveness of the treatment, the duration and severity of potential adverse events and the reversibility of potential adverse events. Note that the hierarchy was not established based on the number of available studies or on the evidence strength for a particular treatment. For example, first-line treatment with behavioral therapy presents essentially no risks to patients and should be offered to all patients. Second-line treatment with oral or transdermal anti-muscarinics or β3-adrenoceptor agonists is not invasive and presents the risk of side effects that primarily compromise quality of life. Any adverse events are readily reversible with cessation of the medication. Third-line treatment with intradetrusor onabotulinumtoxinA is invasive and presents risks for infection as well as increased post-void residuals and the potential need for self-catheterization, which is not quickly reversible. Various neuromodulation therapies (PTNS, SNS) require active participation by a motivated patient. Sacral neuromodulation is invasive and presents the risk of rare adverse events that may not be quickly reversible, such as infection. Additional treatments, such as various kinds of surgery, present the risks of major surgery and are irreversible.

Given that idiopathic OAB is a chronic syndrome without an ideal treatment and no treatment will cure the condition in most patients, clinicians should be prepared to manage the transition between treatment levels appropriately. Treatment failure occurs when the patient does not have the desired change in their symptoms or is unable to tolerate the treatment due to adverse events; lack of efficacy and the presence of intolerable adverse events reduce compliance. The interaction between efficacy, tolerability and compliance is termed clinical effectiveness.38 To optimize effectiveness, it is critical for patients to have realistic expectations regarding likely treatment effects and adverse events.

Bladder diaries that document voiding behavior can be useful to monitor efficacy and guide treatment. In particular, diaries and validated questionnaires can be helpful to quantify baseline symptom levels and treatment effects so that both the patient and the clinician can assess whether a particular treatment approach is alleviating symptoms and whether the balance between symptom control and adverse events is appropriate for a given patient.

This clinical framework does not require that every patient go through each line of treatment in order. There are many factors to consider when identifying the best treatment for a particular patient, including information regarding allergies, sensitivity to various adverse drug events, patient ability and motivation to comply and availability of and access to specific treatments. Behavioral therapies were selected as first-line therapies because they present essentially no risks to the patient. However, behavioral therapies require an investment of time and effort by the patient to achieve maximum benefits and may require sustained and regular contact with the clinician to maintain regimen adherence and consequent efficacy.39 In patients who are unwilling or unable to comply with behavioral therapy regimens and instructions, it is appropriate to move to second-line pharmacologic therapies. Failure and/or the experience of adverse events with one medication should usually be addressed by trying at least one other medication before third-line therapies are considered (see Guideline Statement 11 below). In select patients who are unable or unwilling to comply with pharmacologic management, third-line therapies of neuromodulation (PTNS, SNS) and intradetrusor onabotulinumtoxinA may be considered. Patients who are felt to be reasonable candidates for third-line therapies who have been treated by nonspecialists will require referral to a specialist. In some cases the specialist may opt to obtain further information with voiding diaries or symptom questionnaires, or may do further testing such as urodynamics to rule out other bladder pathologies or urethral dysfunction. The use of indwelling catheters as a management strategy is not recommended except as a last resort in selected patients. Surgical intervention should be reserved for the rare non-neurogenic patient who has failed all other therapeutic options and whose symptoms are intolerable.

First-Line Treatments: Behavioral Therapies

Behavioral treatments are a group of therapies that improve OAB symptoms by changing patient behavior or changing the patient's environment. Most effective behavioral treatment programs include multiple components and are individualized to the unique needs of the patient and his/her unique living situation. There are two fundamental approaches to behavioral treatment for OAB. One approach focuses on modifying bladder function by changing voiding habits, such as with bladder training and delayed voiding.  The other approach, behavioral training, focuses on the bladder outlet and includes pelvic floor muscle training to improve strength and control and techniques for urge suppression. Specific components of behavioral treatment can include self-monitoring (bladder diary), scheduled voiding, delayed voiding, double voiding, pelvic floor muscle training and exercise (including pelvic floor relaxation), active use of pelvic floor muscles for urethral occlusion and urge suppression (urge strategies), urge control techniques (distraction, self-assertions), normal voiding techniques, biofeedback, electrical stimulation, fluid management, caffeine reduction, dietary changes (avoiding bladder irritants), weight loss and other life style changes. In addition, behavioral therapies have the advantage that they can be combined with all other therapeutic techniques. Behavioral therapies are most often implemented by advance practice nurses (e.g., continence nurses) or physical therapists with training in pelvic floor therapy.

Guideline Statement 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

Discussion


Guideline Statement 7

Behavioral therapies may be combined with pharmacologic management. Recommendation

Discussion


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


Guideline Statement 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

Discussion


Guideline Statement 10

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

Discussion


Guideline Statement 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

Discussion


Guideline Statement 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

Discussion


Guideline Statement 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

Discussion


Guideline Statement 14

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

Discussion


Guideline Statement 15

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

Discussion


Guideline Statement 16

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

Discussion


Third-Line Treatments: FDA-Approved

In the patient who has failed behavioral and pharmacologic therapies or who is not a candidate for these therapies, onabotulinumtoxinA therapy , PTNS, or neuromodulation may be offered. The Panel notes that use of these third-line therapies requires careful patient selection and appropriate patient counseling. Clinicians may offer the third-line treatments in any order and may offer the alternate third-line treatment if a patient is refractory to the initial treatment choice. The Panel notes that there is no literature that addresses using these therapies in combination.

Guideline Statement 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-catheterization if necessary. Standard

Discussion


Guideline Statement 18

Clinicians may offer peripheral tibial nerve stimulation (PTNS) as third-line treatment in a carefully selected patient population. Recommendation

Discussion


Guideline Statement 19

Newly FDA-Approved Since the Publication of This Guideline

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

Discussion


Guideline Statement 20

Newly FDA-Approved Since the Publication of This Guideline

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

Discussion


Behavioral, Pharmacologic, and Procedural Treatments in Context

The plots below (Figure 3) are presented to demonstrate the heterogeneity of OAB patients in terms of baseline symptomatology, the different ranges of patients typically treated with the available treatments (other than surgery), the magnitude of placebo effects, and the principle that symptom reductions are proportional to baseline symptom level for UUI episodes, incontinence episodes, and frequency.

Figure 3: Heterogeneity of OAB Patients

Figure 3: Heterogeneity of OAB Patients

Figure 3: Heterogeneity of OAB Patients

Figure 3: Heterogeneity of OAB Patients

Additional Treatments

Guideline Statement 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

Discussion


Guideline Statement 22

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

Discussion


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


Future Directions

Better Stratification of OAB. OAB, because it is a symptom complex, is primarily a diagnosis of exclusion. Treatments are aimed at relieving symptoms and not necessarily at reversing pathophysiologic abnormalities. Understanding the pathophysiology and the risk factors for development of OAB is needed both to treat the syndrome as well as to prevent it. Future research will need to address the entire spectrum of research endeavors including epidemiology, QoL measurements, treatment modalities and basic bladder physiology including sensory and motor signaling. Within the field of OAB, research sometimes is dichotomized between OAB/lower urinary tract symptoms or LUTS (e.g., OAB-dry) versus OAB/urgency incontinence (OAB-wet). However, this type of compartmentalization highlights our lack of understanding of OAB. In other words, are OAB-dry and OAB-wet pathophysiologically related? Is OAB-dry a milder manifestation of the OAB condition which progresses to OAB-wet over time? Or are OAB-dry and OAB-wet two different conditions with different pathophysiologic mechanisms? How can we better objectively measure bladder symptoms? In addition, particularly in females, stress urinary incontinence (SUI) symptoms may exist concomitantly with OAB-symptoms (dry or wet). Further, isolated nocturia is a separate symptom entity, requiring different evaluation and management strategies. This overlap in bladder symptoms is captured in the Venn diagram below with their potential to be concomitantly present. This Venn diagram will appear different based on the gender and age of the population depicted; the diagram included here is intended to provide a point of reference for discussion. Therefore, the phenotype of bladder symptoms should be carefully considered and declared in all research to clarify the particular patient group being studied.

Figure 4: OAB Patient Groups

Figure 4: OAB Patient Groups

Epidemiology. Studies assessing how OAB develops and its natural history and progression are required. The timing and circumstances around which OAB develops and associated risk factors are not yet well-understood. While not specifically targeting epidemiology of OAB, there are large community-based studies that assess prevalence of lower urinary tract symptoms and urinary incontinence.272, 273 By longitudinally studying these community cohorts, these investigators have developed a new hypothesis that lower urinary tract symptoms are likely related to other systemic diseases/conditions.274, 275 Continuation of these types of studies could lead to potential preventive interventions for OAB symptoms and/or utilization of treatments that target the associated systemic conditions rather than the bladder. Epidemiologic studies provide a better cross sectional estimation of the overall population impact of OAB-type symptoms.276

Clinical Research. As discussed previously, several validated OAB-symptom and OAB-symptom bother tools have been developed. However, objective measures of the "cornerstone" OAB-symptom of urgency 277 remains poorly assessed. As defined by the International Continence Society,27 "urgency is the complaint of a sudden compelling desire to pass urine which is difficult to defer." Investigators have tested urgency questionnaires to assess for validity and reliability;278-280 however, no single measure is used consistently across trials, making it difficult to compare findings.

Clinical studies should use validated standardized measures to report subjective outcomes. Objective outcomes should include frequency, nocturia, urgency, incontinence episode frequency and reporting of the variance for each of these measures. Furthermore, the Guideline Panel's meta-analytic efforts were hampered by lack of consistent reporting of variance information (e.g., standard deviations, standard errors of the mean) for baseline and post-treatment measurements.

The effect of treatment of OAB on the elderly, the very frail and those with pre-existing cognitive deficiencies needs further research. These include measures of cognitive side effects from anti-muscarinic treatments.

Basic Science / Translational Research. The finding of a biomarker for OAB would advance the pathophysiologic understanding of OAB. Investigated biomarkers which have been published include nerve growth factor,281 corticotrophin releasing factor,282 prostaglandins 283 and inflammatory factors such as C - reactive protein. 284 Another approach to find potential relevant biomarkers is to utilize high throughput DNA array profiles, using subtractive techniques to identify uniquely expressed genes in OAB (as compared to controls).285 However, this approach is non-targeted and may result in selection of many spurious, non-OAB 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 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.

Tools and Resources

Pocket version of this guideline [pdf]

Additional Educational Resources Available

Overactive Bladder – Clinical Problem Solving (CPS) Protocol

OAB Guideline Update Panel Discussion Webcast [CME] NEW

Provider Toolkits

Journal of Urology®

For Primary Care

Primary Care Update in Urology – Overactive Bladder in the Geriatric Patient

For Patients

It's time to talk about OAB

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