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 Miles Scarpero, Christopher D. Tessier, Sandip Prasan Vasavada

From the American Urological Association Education and Research, Inc., Linthicum, Maryland, and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction

Purpose: The purpose of this guideline is to provide a clinical framework for the Abbreviations diagnosis and treatment of non-neurogenic overactive bladder (OAB). and Acronyms Materials and Methods: The primary source of evidence for this guideline is the AE ϭ adverse event systematic review and data extraction conducted as part of the Agency for ER ϭ extended release Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assess- ϭ ment Number 187 titled Treatment of Overactive Bladder in Women (2009). That FDA Food and Drug report searched PubMed, MEDLINE®, EMBASE and CINAHL for English- Administration language studies published from January 1966 to October 2008. The AUA IR ϭ immediate release conducted additional literature searches to capture treatments not covered in OAB ϭ overactive bladder detail by the AHRQ report and relevant articles published between October PTNS ϭ peripheral tibial nerve 2008 and December 2011. The review yielded an evidence base of 151 treat- stimulation ment articles after application of inclusion/exclusion criteria. When sufficient PVR ϭ post-void residual evidence existed, the body of evidence for a particular treatment was assigned QoL ϭ quality of life a strength rating of A (high), B (moderate) or C (low). Additional treatment SNS ϭ sacral neuromodulation information is provided as Clinical Principles and Expert Opinions when insuf- ϭ ficient evidence existed. UTI urinary tract infection Results: The evidence-based guideline statements are provided for diagnosis and overall management of the adult with OAB symptoms as well as for various The complete guideline is available at http:// treatments. The panel identified first through third line treatments as well as www.auanet.org/content/media/OAB_guideline. pdf. non-FDA approved, rarely applicable and treatments that should not be offered. This document is being printed as submission Conclusions: The evidence-based statements are provided for diagnosis and without independent editorial or peer review by overall management of OAB, as well as for the various treatments. Diagnosis and the Editors of The Journal of Urology®. treatment methodologies can be expected to change as the evidence base grows and as new treatment strategies become obtainable.

Key Words: urinary bladder, overactive; urinary bladder; urinary incontinence; nocturia; guideline

SECTION 1: PURPOSE while minimizing adverse events and THIS guideline’s purpose is to direct spe- patient burden. The most effective ap- cialist and non-specialist clinicians and proach for a particular patient is best patients regarding how to recognize non- determined by the individual clinician neurogenic overactive bladder, conduct a and patient. As the science relevant to valid diagnostic process and establish OAB improves, Guideline amendment treatment goals that maximize symp- will assure the highest contemporary tom control and patient quality of life clinical standards.

0022-5347/12/1886-2455/0 http://dx.doi.org/10.1016/j.juro.2012.09.079 ® THE JOURNAL OF UROLOGY Vol. 188, 2455-2463, December 2012 www.jurology.com 2455 © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. Printed in U.S.A. 2456 AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER

SECTION 2: METHODOLOGY parameters, patient characteristics, AEs and primary out- The primary evidential source for this guideline was the comes were extracted. systematic review and data extraction conducted by the Limitations of the Literature Agency for Healthcare Research and Quality) producing There are significant limitations to the OAB literature. Evidence Report/Technology Assessment Number 187 ti- For example, despite the relatively large number of ran- 1 tled Treatment of Overactive Bladder in Women. Studies domized controlled trials with placebo control groups and focusing on males, nocturia and the use of neuromodula- randomized designs with active controls that assessed tion therapies, including sacral neuromodulation, periph- pharmacologic OAB treatments, the overwhelming major- eral (or posterior) tibial nerve stimulation and intravesical ity of trials followed patients for only 12 weeks. This onabotulinumtoxinA to treat non-neurogenic OAB pa- presents a severe limitation of the literature as OAB is a tients were added to the database. The AUA performed its condition requiring long-term treatment. own qualitative and quantitative analyses of these ex- For a complete discussion of the methodology and evi- tracted data. dence grading, please refer to the full-length version of OAB Diagnosis this guideline available at http://www.auanet.org/content/ The review revealed insufficient evidence-based publica- media/OAB_guideline.pdf. tions to address diagnosis; the diagnosis portions of the algorithm (see figure) are provided as Clinical Principles SECTION 3: BACKGROUND or as Expert Opinions.AClinical Principle is a statement about a component of clinical care that is widely agreed OAB is a clinical diagnosis defined by the Interna- upon by urologists or other expert clinicians for which tional Continence Society as the presence of “urinary there may or may not be evidence in the medical litera- urgency, usually accompanied by frequency and noc- ture. Expert Opinion refers to a statement achieved by turia, with or without urgency urinary incontinence, consensus of the Panel that is based on members’ clinical in the absence of a urinary tract infection (UTI) or training, experience, knowledge and judgment for which other obvious pathology.”2 Methodological differences there is no evidence. across studies challenge any interpretation of the OAB OAB Treatment literature related to epidemiology and treatment. Most A total of 151 articles met the treatment inclusion criteria, studies of OAB, including this guideline, exclude indi- judged a sufficient evidence base to construct the majority viduals with symptoms related to neurologic condi- of the treatment algorithm. Data on study type, treatment tions.

Diagnosis & Treatment Algorithm: AUA Guideline on Non-Neurogenic Overactive Bladder in Adults.

Diagnosis unclear or +/- urine culture, post-void Not OAB or Complicated History and Physical; Urinalysis additional information needed residual, bladder diary, and/or OAB; treat or refer symptom questionnaires

Signs/symptoms of OAB, (-) urine microscopy Signs/symptoms of OAB

Patient education: - Normal urinary tract function - Benefits/risks of treatment alternatives - Agree on treatment goals

Follow-up for efficacy Patient desires treatment and/or and adverse events treatment is in patient’s best interests

Behavioral Treatments In extremely rare cases, Treatment goals met (consider adding anti-muscarinic if partially effective) consider urinary diversion or augmentation cystoplasty Treatment goals not met; Patient desires further treatment and/or further treatment in patient’s best interests

Anti-muscarinics with active management of adverse events (e.g., dry mouth, constipation); consider dose modification or alternate anti-muscarinic if effective but adverse events are intolerable

Treatment goals not met; Patient desires further treatment and/or further treatment in patient’s best interests Consider in carefully-selected patients (multiple therapies may be tried but they should not be combined): Signs/symptoms consistent FDA-Approved: Non-FDA-Approved: Reassess and/or refer; consider urine culture, post-void residual, with OAB diagnosis bladder diary, symptom questionnaires, other diagnostic procedures • Sacral neuromodulation (SNS) or • Intradetrusor as necessary for differentiation • Percutaneous tibial nerve onabotulinumtoxinA stimulation (PTNS) or

The complete OAB Guideline is available at www.AUAnet.org/Guidelines. This resource is supported by an educational grant from Astellas Scientific and Medical Affairs, Inc.

Diagnosis and treatment algorithm AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER 2457

Urgency is the “complaint of a sudden, compelling SECTION 5: DIAGNOSIS desire to pass urine which is difficult to defer.”2 The Diagnostic Approach Urgency is the hallmark symptom of OAB, but it has The section titled Diagnosis is based on Clinical Prin- proven difficult to precisely define or to characterize for research or clinical purposes. Therefore, many ciples or Expert Opinions with consensus achieved studies of OAB treatment response have relied upon using a modified Delphi technique when differences of other measures (eg, number of voids, number of opinion emerged. This section is intended to provide incontinence episodes). clinicians and patients with a framework for deter- Urinary frequency can be reliably measured with mining whether a diagnosis of OAB is appropriate; it a voiding diary. Traditionally, up to seven micturi- is not intended to replace the judgment and experi- tion episodes during waking hours has been consid- ence of the individual clinician faced with a partic- ered normal,3 but this number is highly variable ular patient. based upon hours of sleep, fluid intake, comorbid 1. The clinician should engage in a diagnos- medical conditions and other factors. tic process to document symptoms and signs Nocturia is the interruption of sleep one or more that characterize OAB and exclude other dis- times because of the need to void2 and is a multifac- orders that could be the cause of the patient’s torial symptom often due to factors unrelated to symptoms; the minimum requirements for this OAB, including excessive nighttime urine produc- process are a careful history, physical exam tion and sleep apnea. and urinalysis. Clinical Principle Urgency urinary incontinence is the involuntary The clinician should ascertain the patient’s blad- leakage of urine associated with a sudden compel- der symptoms to document duration of symptoms ling desire to void. Incontinence episodes can be and baseline symptom levels to ensure that symp- measured reliably with a diary. However, in pa- toms are not related to some other condition and to tients with mixed urinary incontinence (both stress determine the complexity of the OAB presentation and urgency incontinence), it can be difficult to dis- that may require referral. Questions should assess tinguish between incontinence subtypes. bladder storage symptoms and bladder emptying. If a patient is not significantly bothered by his/her bladder symptoms, then there is a less compelling SECTION 4: PATIENT PRESENTATION reason to treat the symptoms. Patient reports of bladder function are related to Symptoms amount and type of fluid intake. Excessive fluid When urinary frequency (both daytime and night) intake can produce voiding patterns that mimic and urgency, with or without urgency incontinence, OAB symptoms. A fluid diary can be helpful in this in the absence of UTI or other obvious pathology are regard. Urinary frequency varies across individuals. self-reported as bothersome, the patient may be di- In community-dwelling healthy adults, normal fre- agnosed with OAB.4 quency consists of voiding every three to four hours 5,6 Differentiation with a median of approximately six voids a day. The differential of nocturia includes nocturnal poly- Current medications should be reviewed to ensure uria, low nocturnal bladder capacity or both. In noc- that symptoms are not related to medications. turnal polyuria, nocturnal voids are frequently nor- Co-morbid conditions such as neurologic diseases mal or large volume as opposed to the small volume and other genitourinary conditions should be consid- voids commonly observed in nocturia associated ered as they directly impact bladder function. The with OAB. Sleep disturbances, vascular and/or car- clinician should consider referring these patients to diac disease and other medical conditions are often a specialist for further evaluation and treatment. associated with nocturnal polyuria. Physical examination. A careful, directed physical Frequency that is the result of polydipsia and exam should include an abdominal exam, a rectal/ resulting polyuria may mimic OAB; the two are dis- genitourinary exam and an assessment of lower ex- tinguished with the use of frequency-volume charts. tremities for edema. Polydipsia-related frequency is physiologically self- Cognitive impairment is related to symptom se- induced and should be managed with education and verity with therapeutic implications regarding goals consideration of fluid management. and options. In the Panel’s experience, the ability of While the clinical presentation of interstitial cys- the patient to dress independently is informative of titis/ bladder pain syndrome shares the symptoms of sufficient motor skills related to toileting habits. OAB, bladder and/or pelvic pain, including dyspa- reunia, is a crucial component of its presentation in Urinalysis. A urinalysis to rule out UTI and hema- contradistinction to OAB. turia should be performed. If evidence of hematuria 2458 AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER

not associated with infection is found, then the pa- Treatment failure occurs when the patient with tient should be referred for urologic evaluation. reasonable expectations does not have the antici- 2. In some patients, additional procedures pated symptom improvement or is unable to tolerate and measures may be necessary to validate an the treatment due to AEs; lack of efficacy and the OAB diagnosis, exclude other disorders and presence of intolerable AEs reduce compliance. fully inform the treatment plan. At the clini- 4. OAB is not a disease; it is a symptom com- cian’s discretion, a urine culture and/or post- plex that generally is not a life-threatening void residual assessment may be performed, condition. After assessment has been per- and information from bladder diaries and/or formed to exclude conditions requiring treat- symptom questionnaires may be obtained. ment and counseling, no treatment is an ac- Clinical Principle ceptable choice made by some patients and caregivers. Expert Opinion Urine culture. A urine culture may be appropriate Initiating treatment for OAB presumes that the in certain patients given that a urinalysis may be patient can perceive an improvement in his or her unreliable. QoL. Patients who cannot perceive symptom im- Post-void residual. Measurement of the PVR is not provements may not need any treatment beyond necessary for patients who are receiving first-line toileting and/or diapering, as treatment may be po- behavioral interventions (see Guideline Statement 6 tentially unsafe and/or futile (eg, in the very elderly below) or for uncomplicated patients receiving anti- or demented patient). It is important for clinicians muscarinic medications. PVR should be assessed in who treat this problem to recognize this issue and patients with obstructive symptoms, history of in- set feasible therapeutic goals with the patient and/or continence or prostatic surgery, neurologic diagno- caregiver. ses and at clinician discretion. 5. Clinicians should provide education to pa- Anti-muscarinics should be used with caution in tients regarding normal lower urinary tract patients with PVR Ͼ250–300 mL.7 function, what is known about OAB, the bene- fits vs. risks/burdens of the available treat- Bladder diaries. Diaries that document intake and ment alternatives and the fact that acceptable voiding behavior may be useful, particularly for pa- symptom control may require trials of multi- tient education and to document baseline symptoms ple therapeutic options before it is achieved. and treatment efficacy. Clinical Principle Symptom questionnaires. Validated symptom ques- Successful OAB treatment requires a willing par- tionnaires8–10 are useful in the quantification of ticipant who is informed and engaged in the treat- bladder symptoms and bother changes with OAB ment process, understands that OAB has a variable treatment. and chronic course likely requiring multiple man- 3. Urodynamics, cystoscopy and diagnostic agement strategies over time with no single ideal renal and bladder ultrasound should not be treatment and understands that treatments vary in used in the initial workup of the uncompli- invasiveness, risk of AEs and reversibility. Most cated patient. Clinical Principle OAB treatments improve patient symptoms but are For complicated or refractory patients, the choice unlikely to eliminate all symptoms. Explaining what is normal can help the patient understand their of additional diagnostic tests depends on patient condition and give a comparator for establishing history, QoL and clinician judgment. Neurogenic mutually-identified and realistic goals for treat- OAB requires specific evaluation. Urine cytology is ment. Education empowers the patient to partici- not recommended in the routine evaluation of pa- pate in their treatment, an essential factor when tients with uncomplicated OAB without hematuria interventions rely on behavior change. who respond to therapy. 6. Clinicians should offer behavioral thera- pies (eg, bladder training, bladder control strategies, pelvic floor muscle training, fluid SECTION 6: TREATMENT management) as first-line therapy to all pa- OAB may compromise QoL but generally does not tients with OAB. Standard (Evidence strength: affect survival. A treatment plan, therefore, should Grade B) carefully weigh the patient’s potential benefit of a Behavioral treatments are a group of risk-free tai- particular treatment against that treatment’s risk lorable therapies, which improve individual symptoms for, severity and reversibility of AEs. These guide- by changing patient behavior or the patient’s environ- line statements are a framework to assist in devel- ment. They are first-line treatments because they are oping an individualized treatment plan that opti- as effective in reducing symptom levels as are anti- mizes QoL. muscarinic medications. There are two fundamental AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER 2459

approaches to behavioral treatment. One modifies As similar efficacy was observed for all oral anti- bladder symptoms by changing voiding habits, as muscarinic medications, the choice of medication is with bladder training and delayed voiding. The patient dependent; however, AE profiles for dry other focuses on pelvic floor muscle training to im- mouth and constipation vary with medications. For prove control and techniques for urge suppression. an extensive discussion of side effects, please refer to Both require the active participation of the patient the complete guideline on the AUA website at http:// and/or the patient’s caregiver. www.auanet.org/content/media/OAB_guideline.pdf. While most patients do not experience complete 9. If an immediate release (IR) and an ex- symptom relief, most patients experience signifi- tended release (ER) formulation are available, cant reductions in symptoms and improvements in then ER formulations should preferentially be QoL. The literature provides clear support for the prescribed over IR formulations because of effectiveness of both bladder and behavioral train- lower rates of dry mouth. Standard (Evidence ing.11,12 strength: Grade B) The literature supports the positive effects of A meta-analysis indicates that the ER formula- weight loss on incontinence specifically. A relatively tions of oxybutynin and tolterodine resulted in sta- minor weight loss of 8% in obese woman reduced tistically significantly fewer patient reports of dry overall incontinence episodes per week and urgency mouth than the IR formulations of either medica- urinary incontinence episodes by 47 and 42% vs. 28 tion. and 26% in controls.13 Optimizing medication tolerability is critical to obtaining patient compliance in the treatment of Fluid management with a 25% reduction in fluid 28,29 intake reduced frequency and urgency.14 A bladder this chronic condition. Compliance with a once- training study reducing caffeine intake also resulted daily dosing is greater than with medications taken more than once a day.30 In order to minimize patient in reductions in voiding frequency.15 burden, the decision to prescribe an IR vs. an ER The literature review of comparative effective- formulation should be made in the context of the ness randomized trials indicates that behavioral patient’s prior experience with anti-muscarinics, the treatments are generally either equivalent to16–18 or availability of medications and payer constraints. superior to12,19,20 medications in terms of reducing 10. Transdermal (TDS) oxybutynin (patch or incontinence episodes, improving frequency21–23and gel) may be offered. Recommendation (Evidence nocturia24 and improving QoL. strength: Grade C) 7. Behavioral therapies may be combined TDS preparations of oxybutynin may be offered if with anti-muscarinic therapies. Recommenda- dry mouth is a concern with oral anti-muscarinics. tion (Evidence strength: Grade C) 11. If a patient experiences inadequate symp- A limited literature indicates that initiating be- tom control and/or unacceptable adverse drug havioral and drug therapy simultaneously may im- 19,21,25–27 events with one anti-muscarinic medication, prove outcomes. then a dose modification or a different anti-mus- carinic medication may be tried. Clinical Prin- Second-Line Treatments: Anti-Muscarinics ciple 8. Clinicians should offer oral anti-muscarin- Patients who experience inadequate symptom ics, including darifenacin, fesoterodine, oxy- control and/or unacceptable AEs with one anti-mus- butynin, solifenacin, tolterodine or trospium carinic medication may benefit from a different anti- (listed in alphabetical order; no hierarchy is muscarinic. Dose modification (i.e., reduction and/or implied) as second-line therapy. Standard combination with behavioral techniques) may achieve (Evidence strength: Grade B) a better balance between efficacy and adverse drug Oral anti-muscarinics are second-line therapy, re- events. ducing symptoms but commonly associated with 12. Clinicians should not use anti-muscarin- non-life-threatening side effects (eg, dry mouth, con- ics in patients with narrow angle glaucoma stipation, dry eyes, blurred vision, dyspepsia, UTI, unless approved by the treating ophthalmolo- urinary retention, impaired cognitive function). An gist and should use anti-muscarinics with ex- extensive review of the randomized trials evaluating treme caution in patients with impaired gas- pharmacologic therapies for OAB reveal no compel- tric emptying or a history of urinary retention. ling evidence for differential efficacy across medica- Clinical Principle tions. Prior to initiation of anti-muscarinics, a patient Patients with more severe symptoms, on average, at risk for gastric emptying problems or for urinary experienced greater symptom reductions. Only pa- retention should receive clearance from a gastroen- tients with relatively low baseline symptom levels terologist or urologist, respectively. A PVR may be are likely to experience complete symptom relief. useful in any patient suspected of a higher risk of 2460 AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER

urinary retention. Anti-muscarinics are also contra- AEs, including impaired cognition. In dementia pa- indicated in patients using solid oral forms of potas- tients, anti-muscarinics may be contraindicated en- sium chloride, as the reduced gastric emptying tirely depending on the level of cognitive impair- potentially caused by the anti-muscarinics may ment. increase the potassium absorption of these agents. 16. Patients who are refractory to behav- Anti-muscarinic therapy may be used with caution ioral and medical therapy should be evaluated with alternative forms of potassium chloride. by an appropriate specialist if they desire ad- 13. Clinicians should manage constipation ditional therapy. Expert Opinion and dry mouth before abandoning effective As behavioral therapies present no risks to pa- anti-muscarinic therapy. Management may in- tients and anti-muscarinics present risks that cease clude bowel management, fluid management, when the medication is stopped, the remaining dose modification or alternative anti-musca- treatments present increasing risk that must be bal- rinics. Clinical Principle anced with potential efficacy. Before a patient is Patients should be educated about the possible exposed to these advanced therapies, the patient’s AEs of these medications on bowel function, the realistic desire for further treatment should be as- roles of adequate dietary fiber and fluid, psyllium- certained, and a comprehensive evaluation should based fiber supplements, regular exercise and nor- be conducted to confirm the diagnosis of OAB and mal bowel habits. Treatment advice regarding pos- not another disease process. sible dry mouth could include oral lubricants, Third-Line Treatments avoiding mouthwashes with alcohol, small sips of Neuromodulation or onabotulinumtoxinA therapy water, sucking on sugar-free hard candies and chew- may be offered to the carefully selected patient who ing sugar-free gum. In older patients who may me- has failed behavioral and anti-muscarinic therapy tabolize drugs differently, it is advisable to start or who is not a candidate for these therapies and with a minimal dose and titrate as tolerated. continues to have bothersome symptoms after ap- 14. Clinicians must use caution in prescrib- propriate counseling. Neuromodulation therapies ing anti-muscarinics in patients who are using are FDA-approved for OAB treatment; however, the other medications with anti-cholinergic prop- use of onabotulinumtoxinA in non-neurogenic OAB erties. Expert Opinion patients is not FDA-approved. Medications with anti-cholinergic properties in- clude tricyclic antidepressants, acetylcholinesterase FDA-Approved – Neuromodulation Therapies inhibitors and medications for Parkinsonism, other 17. Clinicians may offer SNS as third-line extra-pyramidal diseases and Alzheimer’s disease. treatment in a carefully selected patient pop- Certain anti-nausea medications and those with at- ulation characterized by severe refractory ropine-like properties may also potentiate AEs. Pre- OAB symptoms or patients who are not candi- scribers should be aware of precautions and contra- dates for second-line therapy and are willing indications for these medications. to undergo a surgical procedure. Recommen- 15. Clinicians should use caution in pre- dation (Evidence strength: Grade C) scribing anti-muscarinics in the frail OAB pa- SNS is FDA-approved in the treatment of OAB. tient. Clinical Principle Studies report that all measured parameters, in- OAB medication trials generally are not con- cluding QoL and subjective improvement, show im- ducted in the frail elderly, resulting in a lack of effi- provement with treatment, but improvement dissi- cacy and AE data in this group. Additional AEs are pates if treatment ceases. reported in this group, including impaired thermoreg- In carefully selected patients, SNS is an appro- ulation with dangerous core temperature elevation. priate therapy with durable treatment effects but Clinicians should begin with the lowest possible dose counterbalanced by frequent and moderately severe and titrate slowly while carefully assessing for the AEs, including pain at the stimulator and lead sites, balance between symptom control and AEs. lead migration, infection/irritation, electric shock, While newer agents (eg, darifenacin) are reported the need for additional surgeries (a side effect that to be less likely to produce cognitive deficits in el- occurred in greater than 30% of patients) and peri- derly patients, the literature is limited; the two- odic battery replacement. Patients must be cogni- week drug administration period in these studies is tively capable of optimizing their device settings and not long enough to yield definitive conclusions.31,32 compliant with the long-term treatment protocols. Patients may not recognize that memory deteriora- Given the negative effects on QoL associated with tion has occurred, making it essential for monitoring severe OAB, the benefits of SNS in the appropriate by the clinician, family members and caregivers.32 patient appear to outweigh the risks/burdens. There Polypharmacy is common in frail community- is some evidence that newer surgical procedures dwelling patients,33 placing them at higher risk for may be associated with fewer AEs.34 AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER 2461

18. Clinicians may offer PTNS as third-line sidered when urinary incontinence has resulted in treatment in a carefully selected patient pop- progressive decubiti. ulation. Option (Evidence strength: Grade C) 21. In rare cases, augmentation cystoplasty The most common protocol reviewed was the ap- or urinary diversion for severe, refractory, plication of 30 minutes of stimulation once a week complicated OAB patients may be considered. for 12 weeks. Longer follow-up periods of time in two Expert Opinion studies indicate that improvements are maintained Surgery is not recommended for OAB patients with on-going treatment.35–38 The validity of PTNS except in extremely rare cases as there are substan- treatment responses is supported by a study com- tial risks to these procedures, including the likely paring a PTNS group to a sham-PTNS group wherein need for long-term intermittent self-catheterization only the active treatment group exhibited improve- and the risk of malignancy.39 The vast majority of ments in OAB symptoms.38 AEs were relatively un- case series of augmentation cystoplasty and diver- common and mild. PTNS can benefit a carefully se- sion focus on neurogenic patients. Little is known lected group of patients with moderately severe regarding the impact of these procedures on non- baseline incontinence and frequency and willingness neurogenic OAB patients and, particularly, on their to comply with the PTNS protocol as well as those QoL. having resources allowing for frequent office visits Follow-Up for on-going treatment. 22. The clinician should offer follow-up with the patient to assess compliance, efficacy, side Non-FDA-Approved: Intradetrusor injection of effects and possible alternative treatments. onabotulinumtoxinA Expert Opinion 19. Clinicians may offer intradetrusor on- Follow-up is useful in assessing treatment com- abotulinumtoxinA as third-line treatment in pliance, questioning patients regarding the balance the carefully selected and thoroughly coun- between symptom improvements and AEs and pre- seled patient who has been refractory to first- senting information about possible alternative treat- and second-line OAB treatments. The patient ments for patients with insufficient symptom improve- must be able and willing to return for frequent ment and/or intolerable AEs. Patients should be PVR evaluation and able and willing to per- encouraged to persist with a particular treatment for form self-catheterization, if necessary. Option four to eight weeks; this time period will identify the (Evidence strength: Grade C) majority of responders.40 At the time of this writing, intradetrusor on- abotulinumtoxinA is not FDA-approved for treat- ment of non-neurogenic OAB. SECTION 7: RESEARCH NEEDS AND Reductions in frequency, nocturia, pad use and FUTURE DIRECTIONS incontinence, improvement in urodynamics param- The panel recognizes that much additional research eters and improvement in QoL measures diminish is needed in OAB including epidemiologic, basic sci- over time requiring repeat injections to restore im- ence, translational and clinical research. For a de- provements. Substantial rates of AEs occurred in tailed description of research needs and future direc- the active treatment groups and included UTIs, el- tions please refer to the full-length version of this evated PVR and the need for self-catheterization. guideline available at http://www.auanet.org/content/ media/OAB_guideline.pdf. Additional Treatments 20. Indwelling catheters (including transure- Conflict of Interest Disclosures thral, suprapubic, etc.) are not recommended All panel members completed COI disclosures. Re- as a management strategy for OAB because of lationships that have expired (more than one year the adverse risk/benefit balance except as a old) since the panel’s initial meeting, are listed. last resort in selected patients. Expert Opinion Those marked with (C) indicate that compensation Management with diapering and absorbent gar- was received; relationships designated by (U) indi- ments is always preferred to indwelling catheteriza- cate no compensation was received. tion because of the high risk of indwelling catheter- Consultant/Advisor: Toby C. Chai, Allergan associated UTIs, urethral erosion/destruction and (C), Medtronic (C), Ion Channel, Inc. (C), Astellas urolithiasis. Intermittent catheterization may be an (C)(expired); Harriette M. Scarpero, American option when concomitant incomplete bladder emp- Medical Systems (AMS) (C), Allergan (C); J. Quen- tying leads to overflow incontinence; however, this tin Clemens, Medtronic , (C), Amphora Medical (C), approach generally requires either patient willing- United Biosource Corporation (C)(expired), Pfizer ness and ability or significant caregiver support. As (C) (expired), Afferent Pharmaceuticals, Inc. (C) a last resort, an indwelling catheter might be con- (expired); Daniel J. Culkin, American Medical Sys- 2462 AUA/SUFU GUIDELINE ON OVERACTIVE BLADDER

tems (AMS) (C); Sandip P. Vasavada, American vic Medicine & Urogenital Reconstruction. Commit- Medical Systems (C), Allergen (C); Boston Scientific tee members received no remuneration for their (C)(expired); Kathryn L. Burgio, Johnson & John- work. Each member of the committee provides an son (C), Astellas (C), Pfizer (C) ongoing conflict of interest disclosure to the AUA. Investigator: J. Quentin Clemens, Pfizer (C) While these guidelines do not necessarily estab- (expired); Daniel J. Culkin, Watson Pharmaceuti- lish the standard of care, AUA seeks to recommend cals (U)(expired) and to encourage compliance by practitioners with Meeting Participant or Lecturer: Harriette current best practices related to the condition being M. Scarpero, Allergan (C), Pfizer (C)(expired), As- treated. As medical knowledge expands and technol- tellas US, (C)(expired), Lilly (C)(expired); Daniel J. ogy advances, the guidelines will change. Today, Culkin, American Medical Systems (AMS) (C); Al- these evidence-based guideline statements repre- lergan, Pfizer (C), Allergen (C); Kathryn L. Burgio, sent not absolute mandates but provisional propos- Pfizer (C) als for treatment under the specific conditions de- Scientific Study or Trial: Elizabeth Ann scribed in each document. For all these reasons, the Gormley, National Institute of Health - NIDDK (C); guidelines do not pre-empt physician judgment in Toby C. Chai, Allergan (C), National Institutes of individual cases. Health (U); Harriette M. Scarpero, Pfizer (U), Treating physicians must take into account vari- Daniel J. Culkin, Medtronic (U), Taris Pharma- ceuticals (C); Sandip P. Vasavada, allergen (C); ations in resources, and patient tolerances, needs, Kathryn L. Burgio, Pfizer (C) and preferences. Conformance with any clinical Investment Interest: Deborah J. Lightner, guideline does not guarantee a successful outcome. Amgen (C)(expired), Vertex Pharmaceuticals (C)(ex- The guideline text may include information or rec- pired), Celgene (C)(expired); J. Quentin Clemens, ommendations about certain drug uses (‘off label’) Merck (U); Anurag Kumar Das, Amgen (U), No- that are not approved by the FDA, or about medica- vartis (U), Sanofi-Aventis (U), Astellas (U), Johnson tions or substances not subject to the FDA approval and Johnson (U), Novo Nordisk (U); Sandip P. Vasa- process. AUA urges strict compliance with all gov- vada, NDI Medical LLC (C); Christopher D. Tes- ernment regulations and protocols for prescription sier, United Medical Systems (C), Healthtronics (C) and use of these substances. The physician is en- Other: Toby C. Chai, Taris Biomedical (C) couraged to carefully follow all available prescribing information about indications, contraindications, Disclaimer precautions and warnings. These guidelines are not This document was written by the Overactive Blad- intended to provide legal advice about use and mis- der Guidelines Panel of the American Urological Association Education and Research, Inc., which use of these substances. was created in 2009. The Practice Guidelines Com- Although guidelines are intended to encourage mittee of the AUA selected the panel chair. Panel best practices and potentially encompass available members were selected by the chair. Membership of technologies with sufficient data as of close of the the panel included urologists and other clinicians literature review, they are necessarily time-limited. with specific expertise on this disorder. The mission Guidelines cannot include evaluation of all data on of the committee was to develop recommendations emerging technologies or management, including that are analysis-based or consensus-based, depend- those that are FDA-approved, which may immedi- ing on Panel processes and available data, for opti- ately come to represent accepted clinical practices. mal clinical practices in the diagnosis and treatment For this reason, the AUA does not regard technol- of overactive bladder. ogies or management which are too new to be ad- Funding of the committee was provided by the dressed by these guidelines as necessarily experi- AUA and the Society for Urodynamics, Female Pel- mental or investigational.

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