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Optimizing Nonsurgical Treatments of Overactive Bladder in the United States

Open AccessPublished:June 26, 2020DOI:https://doi.org/10.1016/j.urology.2020.06.017

      Abstract

      Overactive bladder syndrome is a prevalent condition impacting quality of life, activities of daily living, work productivity, physical and psychological health, sleep, and sexuality. Published guideline recommendations and effective behavioral, pharmacologic, and neuromodulatory therapies exist; however, adherence can be poor. Clinicians have important roles educating patients, setting treatment expectations, and providing follow-up. Determining patient goals, routinely assessing and adjusting therapy, and combining treatment strategies may improve outcomes. We review the benefits and challenges of overactive bladder treatments and propose approaches to improve patient management, with the goals of initiating therapy earlier and achieving better patient satisfaction, functioning, and quality of life.
      The International Continence Society defines overactive bladder (OAB, urgency) syndrome as “urinary urgency, usually accompanied by increased daytime frequency and/or nocturia, with urinary incontinence (UI) (OAB-wet) or without (OAB-dry), in the absence of a urinary tract infection or other detectable disease.”
      • Haylen BT
      • de Ridder D
      • Freeman RM
      • et al.
      An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction.
      In the United States (US), the prevalence of OAB syndrome estimated in the National Overactive Bladder Evaluation Program was 16.5%, comprising 6.1% OAB-wet and 10.4% OAB-dry.
      • Stewart WF
      • Van Rooyen JB
      • Cundiff GW
      • et al.
      Prevalence and burden of overactive bladder in the United States.
      OAB has a broad impact on quality of life (QOL) and activities of daily living, work productivity, physical and psychological health, sleep, and sexuality.
      • Dmochowski RR
      • Newman DK
      Impact of overactive bladder on women in the United States: results of a national survey.
      • Coyne KS
      • Sexton CC
      • Irwin DE
      • et al.
      The impact of overactive bladder, incontinence, and other lower urinary tract symptoms on quality of life, work productivity, sexuality, and emotional well-being in men and women: results from the EPIC study.
      • Sexton CC
      • Coyne KS
      • Vats V
      • et al.
      Impact of overactive bladder on work productivity in the United States: results from EpiLUTS.
      • Milsom I
      • Kaplan SA
      • Coyne KS
      • Sexton CC
      • Kopp ZS
      Effect of bothersome overactive bladder symptoms on health-related quality of life, anxiety, depression, and treatment seeking in the United States: results from EpiLUTS.
      • Lai HH
      • Rawal A
      • Shen B
      • Vetter J
      The relationship between anxiety and overactive bladder or urinary incontinence symptoms in the clinical population.
      • Lai HH
      • Shen B
      • Rawal A
      • Vetter J
      The relationship between depression and overactive bladder/urinary incontinence symptoms in the clinical OAB population.
      Published guidelines provide recommendations regarding assessment, management, and follow-up of patients with OAB syndrome. Those established by the American Urological Association (AUA)/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); the Canadian Urological Association; and the Society of Obstetricians and Gynaecologists of Canada are specific for OAB syndrome; although AUA/SUFU notes that study data are limited for urgency and nocturia.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      • Geoffrion R
      No. 283-treatments for overactive bladder: focus on pharmacotherapy.
      Guidelines from the American College of Physicians, the International Consultation on Incontinence, and the National Institute for Health and Care Excellence (NICE), originally developed for UI, include recommendations for OAB syndrome and/or urgency UI (OAB-wet).
      • Qaseem A
      • Dallas P
      • Forcia MA
      • et al.
      Nonsurgical management of urinary incontinence in women: a clinical practice guideline from the American College of Physicians.
      • Abrams P
      • Andersson KE
      • Apostolidis A
      • et al.
      6th International Consultation on Incontinence. Recommendations of the International Scientific Committee: evaluation and treatment of urinary incontinence, pelvic organ prolapse, and faecal incontinence.

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      The guidelines generally recommend initial patient assessment through a history and physical, along with a urinalysis to rule out infection.
      • Syan R
      • Brucker BM
      Guideline of guidelines: urinary incontinence.
      Additional assessments include a urine culture (if indicated), post-void residual assessment, bladder diary, and/or symptom questionnaire.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      ,
      • Abrams P
      • Andersson KE
      • Apostolidis A
      • et al.
      6th International Consultation on Incontinence. Recommendations of the International Scientific Committee: evaluation and treatment of urinary incontinence, pelvic organ prolapse, and faecal incontinence.
      ,

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      If results suggest OAB, patients should receive education on normal bladder function and benefits and risks of treatment. The clinician and patient should discuss the patient's treatment goals and expectations.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Abrams P
      • Andersson KE
      • Apostolidis A
      • et al.
      6th International Consultation on Incontinence. Recommendations of the International Scientific Committee: evaluation and treatment of urinary incontinence, pelvic organ prolapse, and faecal incontinence.
      First-line treatment for OAB consists of lifestyle changes, including weight loss, dietary and fluid management, smoking cessation, bowel regularity, and behavioral therapy, including bladder training with urgency suppression strategies, and pelvic floor muscle (PFM) training with stress strategies (eg, the knack) to prevent leakage. Recommended second-line treatment consists of pharmacologic therapy with antimuscarinic agents (oral, extended-release, and transdermal formulations) and/or β3-adrenergic agonists.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      • Geoffrion R
      No. 283-treatments for overactive bladder: focus on pharmacotherapy.
      • Qaseem A
      • Dallas P
      • Forcia MA
      • et al.
      Nonsurgical management of urinary incontinence in women: a clinical practice guideline from the American College of Physicians.
      ,

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      Behavioral and pharmacologic therapy may be combined.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      In cases of inadequate efficacy/tolerability or refractoriness, switching agents or considering combining an antimuscarinic agent with a β3-adrenergic agonist is recommended.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      Third-line approaches in carefully selected patients are peripheral tibial nerve stimulation (PTNS), intradetrusor onabotulinumtoxinA injection, and sacral nerve stimulation (SNS).

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      • Geoffrion R
      No. 283-treatments for overactive bladder: focus on pharmacotherapy.
      The AUA/SUFU guideline recommends scheduled follow-up visits to assess adherence, treatment efficacy and side effects, and need for alternative treatments. Comparison of symptoms after 8-12 weeks of behavioral therapy or 4-8 weeks of pharmacologic therapy with baseline measures on bladder diaries, global response scales, or OAB-specific instruments enable efficacy assessment. Clinicians should ask patients about side effects or difficulties with treatment, provide appropriate adjustments, and emphasize that treatment success depends on adherence.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      Patients should be reminded that treatment benefits may not be apparent until 12 weeks after initiation, while adverse effects often occur earlier.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      The NICE guideline recommends evaluation of bladder training at a minimum of 6 weeks, and continuation of supervised PFM training for at least 3 months. After initiation of pharmacologic therapy, a telephone or face-to-face review at 4 weeks (earlier for intolerable side effects) and every 12 months (every 6 months for patients aged >75 years) is recommended.

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      Clinicians may encounter several practical issues that the guidelines do not fully address, such as how best to determine patient goals, assess patient satisfaction and bothersome symptoms, promote adherence to therapy, and optimize timing of follow-up visits. We will discuss these points and review the recommended treatment approaches.

      BARRIERS TO KEEPING PATIENTS ON TREATMENT

      Despite the availability of effective therapies for OAB syndrome, patients may have barriers to use. Some may never start prescribed treatment; an analysis of electronic medical records from a US managed care health care system found that 18% of patients aged ≥18 years prescribed a new OAB medication did not pick up their prescription within 30 days.
      • Rashid N
      • Vassilakis M
      • Lin KJ
      • et al.
      Primary nonadherence to overactive bladder medications in an integrated managed health care system.
      Among patients who initiate treatment, many do not return for follow-up, discontinue therapy before the end of the recommended trial period, and do not pursue third-line therapy. Factors influencing treatment discontinuation include age, comorbidities, cost, drug interactions, adverse effects, and inadequate efficacy.
      • Hsu FC
      • Weeks CE
      • Selph SS
      • et al.
      Updating the evidence of drugs to treat overactive bladder: a systematic review.
      In addition, it is not uncommon for patients to stop medication after a few days because of no change in symptoms.
      • Filipetto FA
      • Fulda KG
      • Holthusen A
      • et al.
      The patient perspective on overactive bladder: a mixed-methods needs assessment.
      Before a plan of care is prescribed, it is essential for the clinician and patient to have a discussion to (1) determine mutually agreed-upon treatment goals, (2) set treatment expectations, and (3) ensure understanding of what is required for therapy to be successful. Patients should understand that OAB syndrome can have a variable course that must be managed over time, no one therapy is ideal for everyone, and therapies vary in level of required effort, side effects, and reversibility.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      Data support that patients who communicate more frequently with clinicians have higher levels of treatment adherence.
      • Filipetto FA
      • Fulda KG
      • Holthusen A
      • et al.
      The patient perspective on overactive bladder: a mixed-methods needs assessment.
      Although the AUA/SUFU guideline notes that OAB is not a disease, and electing for no treatment does represent an acceptable choice,

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      it is important to recognize that OAB has multiple negative effects on patients’ lives. Compared with women without OAB symptoms, women with OAB symptoms report significantly lower self-esteem, declining health, imposition on family members, disturbed sleep or insomnia, low interest in sex, and an impact of OAB on QOL.
      • Dmochowski RR
      • Newman DK
      Impact of overactive bladder on women in the United States: results of a national survey.
      OAB also has been associated with anxiety,
      • Lai HH
      • Rawal A
      • Shen B
      • Vetter J
      The relationship between anxiety and overactive bladder or urinary incontinence symptoms in the clinical population.
      depression,
      • Lai HH
      • Shen B
      • Rawal A
      • Vetter J
      The relationship between depression and overactive bladder/urinary incontinence symptoms in the clinical OAB population.
      and interference with work productivity.
      • Sexton CC
      • Coyne KS
      • Vats V
      • et al.
      Impact of overactive bladder on work productivity in the United States: results from EpiLUTS.
      OAB syndrome also confers an increased risk of incontinence-associated dermatitis, urinary tract infection, falls, and fracture. The latter may be particularly important in older patients, who have higher levels of functional impairment and physical limitations than those without OAB.
      • Jayadevappa R
      • Chhatre S
      • Newman DK
      • et al.
      Association between overactive bladder treatment and falls among older adults.
      Conversely, comorbidities and concomitant medications may complicate OAB treatment in older individuals. A real-world study found that during a 1-year time period, OAB patients aged ≥65 years experienced an average of 18 comorbid conditions compared with 11 for those without OAB, requiring an average of 12 concomitant medications compared with 8 for those without OAB.
      • Ganz ML
      • Liu J
      • Zou KH
      • et al.
      Real-world characteristics of elderly patients with overactive bladder in the United States.
      An analysis of patients aged ≥65 years visiting an academic nononcology urology practice identified an association between frailty and OAB (adjusted odds ratio, 3.0), independent of age, sex, race, and number of medications.
      • Suskind AM
      • Quanstrom K
      • Zhao S
      • et al.
      Overactive bladder is strongly associated with frailty in older individuals.

      FIRST-LINE THERAPY: BEHAVIORAL INTERVENTIONS

      Behavioral interventions require a considerable time commitment and continued patient effort for success, but they are effective, non-invasive, reversible, and not associated with bothersome or serious adverse events (AEs).

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      They are broadly categorized as behavior changes and training techniques.
      • Wyman JF
      • Burgio KL
      • Newman DK
      Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.
      Behavior changes are diet/lifestyle modifications, such as restriction of fluid and caffeine intake, dietary management, weight loss, and scheduled voiding via a bladder diary for a fixed schedule of urination regardless of need.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      ,

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      ,
      • Wyman JF
      • Burgio KL
      • Newman DK
      Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.
      Training techniques are urge suppression strategies, bladder training, and PFM training with stress strategies. Urge suppression strategies include relaxation techniques (eg, deep breathing), distraction tasks (eg, balancing a checkbook, games, and puzzles), affirmations (eg, “I can control this”), and quick PFM contractions.
      • Wyman JF
      • Burgio KL
      • Newman DK
      Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.
      The aim of bladder training is to restore normal bladder function by improving central nervous system control of function and/or increasing bladder reserve capacity.
      • Newman DK
      • Borello-France D
      • Sung VW
      Structured behavioral treatment research protocol for women with mixed urinary incontinence and overactive bladder symptoms.
      Patients use a bladder diary to follow a timed voiding schedule on which the time between voids is gradually increased, using urge suppression strategies as needed, with a goal of achieving a 3-4-hour voiding interval.
      • Wyman JF
      • Burgio KL
      • Newman DK
      Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.
      The aim of PFM training is to inhibit detrusor contraction through a PFM contraction.
      • Fitz F
      • Sartori M
      • Girão MJ
      • Castro R
      Pelvic floor muscle training for overactive bladder symptoms – a prospective study.
      With augmented biofeedback, patients are taught to contract and relax the PFMs on a daily basis (15 contractions 3 times a day) to increase strength and coordination and to prevent urine leakage by performing a single well-timed PFM contraction prior to an incontinence-triggering event.
      • Wyman JF
      • Burgio KL
      • Newman DK
      Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.
      ,
      • Newman DK
      • Borello-France D
      • Sung VW
      Structured behavioral treatment research protocol for women with mixed urinary incontinence and overactive bladder symptoms.
      ,
      • Miller JM
      • Sampselle C
      • Ashton-Miller JA
      • et al.
      Clarification and confirmation of the knack maneuver: the effect of volitional pelvic floor muscle contraction to preempt expected stress incontinence.
      These interventions are often administered by specifically trained advanced practice providers.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      The efficacy of behavioral therapies is well established; however, the majority of behavioral therapy studies lack an appropriate placebo control. In the 1990s, Fantl et al showed that among women aged 55-90 years with UI who received 6 weeks of bladder training and were instructed to use relaxation and distraction for urgency episodes, 75% had a ≥50% reduction in incontinent episodes, which was associated with improvements in QOL scores. With the exception of nocturnal voluntary micturition, all treatment effects were maintained for 6 months.
      • Fantl JA
      • Wyman JF
      • McClish DK
      • et al.
      Efficacy of bladder training in older women with urinary incontinence.
      In a study of 12 weeks of PFM training in women aged 41-77 years with OAB symptoms, significant improvements in PFM function were measured, along with significant improvements in the severity of UI, OAB symptoms, urinary leakage, nocturia, and QOL.
      • Fitz F
      • Sartori M
      • Girão MJ
      • Castro R
      Pelvic floor muscle training for overactive bladder symptoms – a prospective study.
      The efficacy of behavioral therapies appears similar to that of current pharmacologic therapy. A comparison of outcomes 4 years after women with OAB-wet received 3 months of treatment with one of 4 methods (drug therapy; bladder training; PFM training; or a combination of bladder training, PFM training and behavioral advice) showed no differences among treatments in improvements from baseline on number of voids per day, number of urgency UI episodes per week, completely dry rate, or QOL.
      • Azuri J
      • Kafri R
      • Ziv-Baran T
      • Stav K
      Outcomes of different protocols of pelvic floor physical therapy and anti-cholinergics in women with wet over-active bladder. A 4-year follow-up.
      The main limitation of behavioral therapies centers on low adherence,
      • Borello-France D
      • Burgio KL
      • Goode PS
      • et al.
      Adherence to behavioral interventions for urge incontinence when combined with drug therapy: adherence rates, barriers, and predictors.
      ,
      • Dumoulin C
      • Hay-Smith J
      • Frawley H
      • et al.
      2014 consensus statement on improving pelvic floor muscle training adherence: International Continence Society 2011 State-of-the-Science Seminar.
      as patients must be willing to alter their lifestyle and have the discipline to maintain the changes. Another limitation is that training in administration of behavioral therapies takes time for the clinician. Selected resources available to clinicians on this topic are listed in Table 1.
      Table 1Selected behavioral therapy resources for clinicians
      ResourceDescriptionURL
      SUFU overactive bladder clinical care pathwayA 2-page clinical care pathway for OAB that summarizes the diagnostic approach, provides information on patient education, and reviews options for first-line or initial treatment, second-line treatment (medication), and third-line or advanced therapies.

      SUFU Center of Excellence main page that includes a link to download the clinical care pathway provider flowchart as a PDF.
      https://sufuorg.com/docs/oab/sufu-oab-flyer.aspx

      https://www.urotoday.com/center-of-excellence/sufu.html
      AUA core curriculum for advanced practice providersWeb page that contains links to the AUA's educational resources for advanced practice providers and allied health professionals.https://www.auanet.org/education/auauniversity/for-app/allied-health-professionals
      SUNA Core Curriculum for Urologic NursingTextbook that contains 51 chapters of information on pediatric and adult urologic assessment and diseases for urologic professionals.https://www.suna.org/core-curriculum-urologic-nursing
      SUNA continuing education courses

      (eg, SUNA pelvic muscle rehabilitation workshop)
      Online library that has continuing education materials.https://library.suna.org/suna/sessions/4337/view
      AUA, American Urological Association; OAB, overactive bladder; SUFU, Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction; SUNA, Society of Urologic Nurses and Associates.

      SECOND-LINE THERAPY: PHARMACOLOGIC TREATMENT

      Antimuscarinic Agents

      Antimuscarinic agents indicated for the treatment of OAB in the US are oxybutynin, solifenacin, darifenacin, tolterodine, fesoterodine, and trospium. These agents block the binding of acetylcholine to the muscarinic cholinergic receptor at the neuromuscular junction to aid in detrusor relaxation. They also may inhibit the activity of urothelial sensory receptors to block sensory signaling.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      Because muscarinic receptors are present throughout the body, associated side effects are based on actions at those sites (eg, dry mouth, dry eyes, blurred vision, constipation, and impaired cognitive function).
      Results of randomized trials of antimuscarinic agents in patients with OAB syndrome suggest that the agents have similar efficacy.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      • Geoffrion R
      No. 283-treatments for overactive bladder: focus on pharmacotherapy.
      • Qaseem A
      • Dallas P
      • Forcia MA
      • et al.
      Nonsurgical management of urinary incontinence in women: a clinical practice guideline from the American College of Physicians.
      A systematic review and meta-analysis of 50 randomized controlled trials in women found that in general, antimuscarinic agents had modest efficacy in improving one or more OAB symptoms, including daily episodes of urge UI and voids per day, and although full resolution of symptoms was rare, treatment was associated with improvements in QOL. Significant improvements in episodes of urgency UI and daily voids also were found with placebo.
      • Reynolds WS
      • McPheeters M
      • Blume J
      • et al.
      Comparative effectiveness of anticholinergic therapy for overactive bladder in women: a systematic review and meta-analysis.
      The reason for the placebo effect was unclear, but patient self-use of behavioral therapy techniques, including monitoring symptoms with a diary, during the trials may have contributed. Indeed, statistically significant placebo effects were commonly observed in an analysis of 62 randomized controlled trials of antimuscarinic agents in OAB syndrome, with numerous potential explanations.
      • Mangera A
      • Chapple CR
      • Kopp ZS
      • Plested M
      The placebo effect in overactive bladder syndrome.
      Antimuscarinic agents may take several weeks to achieve an initial treatment effect. Given the similar efficacy among agents, treatment choices should be based on patient history, comorbidities, and impact of AEs of specific drugs.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      • Geoffrion R
      No. 283-treatments for overactive bladder: focus on pharmacotherapy.
      Information on long-term side effects in patients with OAB is limited because most of the randomized controlled trials were 12 weeks in duration.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      • Geoffrion R
      No. 283-treatments for overactive bladder: focus on pharmacotherapy.
      Adherence to oral medications can be low. In a survey of 1322 US individuals aged ≥18 years who had discontinued antimuscarinic agents for OAB in the past 12 months, the most common reasons for discontinuation were “it didn't work as expected” (46%), “switched to a new medication” (25%), “learned to get by without medication” (23%), and “I had side effects” (21%).
      • Benner JS
      • Nichol MB
      • Rovner ES
      • et al.
      Patient-reported reasons for discontinuing overactive bladder medication.
      A study of 42,886 new users aged ≥66 years in a Medicare fee-for-service population found that within 1 year of initiation, 72% had discontinued therapy, and only 14% were continuously using their initially prescribed agent.
      • Vouri SM
      • Schootman M
      • Strope SA
      • et al.
      Antimuscarinic use and discontinuation in an older adult population.
      Follow-up may help maintain adherence; however, a survey of 301 Canadian urologists and gynecologists found that only 28% had a follow-up visit with their patients 4-8 weeks after treatment initiation, and 30% did not do so until more than 12 weeks after initiation.
      • Przydacz M
      • Campeau L
      • Walter JE
      • Corcos MD
      How long do we have to treat overactive bladder syndrome? A questionnaire survey of Canadian urologists and gynecologists.
      Formulation has a role in promoting adherence, as an analysis of patients aged ≥18 years with at least one pharmacy claim for an immediate-release (IR) or extended-release (ER) formulation of oxybutynin or tolterodine showed that adherence with ER formulations was significantly better than with IR formulations.
      • D'Souza AO
      • Smith MJ
      • Miller LA
      • et al.
      Persistence, adherence, and switch rates among extended-release and immediate-release overactive bladder medications in a regional managed care plan.
      The main limitations of these agents are side effects. The AUA/SUFU guideline recommends managing dry mouth and constipation with fluid management and bowel management, respectively, and dose modification before abandoning an effective therapy. ER and transdermal formulations are recommended to decrease the incidence of dry mouth.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      Antimuscarinics also are associated with an increased risk of depression and cognitive impairment. A retrospective cohort study of women with OAB syndrome found that use was associated with a 1.38-fold increased risk of a diagnosis of depressive disorder within 3 years of treatment initiation versus no use.
      • Chung SD
      • Weng SS
      • Huang CY
      • et al.
      Antimuscarinic use in females with overactive bladder syndrome increases the risk of depressive disorder: a 3-year follow-up study.
      A nested case-control study of individuals aged 55-100 years exposed to anticholinergic agents demonstrated that long-term use (vs nonuse) of bladder antimuscarinic drugs was associated with an increased risk of dementia (adjusted odds ratio, 1.65 in the highest exposure category).
      • Coupland CAC
      • Hill T
      • Dening T
      • et al.
      Anticholinergic drug exposure and the risk of dementia: a nested case-control study.
      The American Geriatrics Society Beer's criteria, which provide guidance on potentially inappropriate medication use in adults ≥65 years of age, specify that antimuscarinic agents may exacerbate dementia or cognitive impairment.
      American Geriatrics Society Beers Criteria® Update Expert Panel
      American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults.
      These findings signal a need for increased caution with anticholinergic agents in older individuals, as a 2015 US OAB-related medication claims analysis determined that the most common medications dispensed to individuals aged 65-104 years were oxybutynin (38%), solifenacin (20%), and tolterodine (19%).
      • Kinlaw AC
      • Funk MJ
      • Conover MM
      • et al.
      Impact of new medications and $4 generic programs on overactive bladder treatment among older adults in the United States, 2000–2015.
      The AUA/SUFU guideline cautions against the use of anticholinergic agents in patients taking other medications with anticholinergic properties and in frail patients,

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      and the Canadian Urological Association guideline provides considerations for frail older patients.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      The AUA/SUFU guideline designates the effect of treatment of OAB in older patients and the cognitive side effects of antimuscarinic treatments as areas requiring further research.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      β3-Adrenoceptor Agonists

      Stimulation of β3-adrenoceptor activity results in bladder relaxation, which improves filling and storage.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      Adrenergic agonists with β3-adrenoceptor selectivity achieve these effects to improve OAB symptoms without the side effects characteristic of antimuscarinic agents. This may be particularly important in older patients, given the concerns with antimuscarinic agents discussed above. Mirabegron was the first β3-adrenoreceptor agonist approved in the US in 2012 for treatment of OAB with symptoms of urgency UI, urgency, and urinary frequency. Mirabegron 25 mg once daily in combination with the antimuscarinic agent solifenacin 5 mg once daily also was approved in the US for this indication in 2018; the prescribing information states that the mirabegron dose may be increased to 50 mg once daily after 4-8 weeks, according to individual efficacy and tolerability.
      MYRBETRIQ® (Mirabegron Extended-Release Tablets) Prescribing Information.
      Mirabegron monotherapy was evaluated in 3, 12-week, double-blind, placebo-controlled studies
      • Nitti VW
      • Auerbach S
      • Martin N
      • et al.
      Results of a randomized phase III trial of mirabegron in patients with overactive bladder.
      • Khullar V
      • Amarenco G
      • Angulo JC
      • et al.
      Efficacy and tolerability of mirabegron, a β(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial.
      • Herschorn S
      • Barkin J
      • Castro-Diaz D
      • et al.
      A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder.
      and a 1-year, randomized, fixed-dose, double-blind, active-controlled safety study.
      • Chapple CR
      • Kaplan SA
      • Mitcheson D
      • et al.
      Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder.
      Mirabegron achieved significant decreases from baseline versus placebo in mean number of incontinence episodes and micturitions per 24 hours
      • Nitti VW
      • Auerbach S
      • Martin N
      • et al.
      Results of a randomized phase III trial of mirabegron in patients with overactive bladder.
      • Khullar V
      • Amarenco G
      • Angulo JC
      • et al.
      Efficacy and tolerability of mirabegron, a β(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial.
      • Herschorn S
      • Barkin J
      • Castro-Diaz D
      • et al.
      A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder.
      ; significant decreases in incontinence episodes were apparent as early as 4 weeks after treatment initiation for the 50-mg dose and at 8 weeks for the 25-mg dose.
      • Herschorn S
      • Barkin J
      • Castro-Diaz D
      • et al.
      A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder.
      Mirabegron plus solifenacin was studied in 3, 12-week double-blind, randomized, active-controlled studies
      • Abrams P
      • Kelleher C
      • Staskin D
      • et al.
      Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony).
      • Drake MJ
      • Chapple C
      • Esen AA
      • et al.
      Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BEDSIDE).
      • Herschorn S
      • Chapple CR
      • Abrams P
      • et al.
      Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study).
      and a 1-year, double-blind, randomized, active-controlled study.
      • Gratzke C
      • van Maanen R
      • Chapple C
      • et al.
      Long-term safety and efficacy of mirabegron and solifenacin in combination compared with monotherapy in patients with overactive bladder: a randomised, multicentre, phase 3 study (SYNERGY II).
      The combination significantly reduced mean numbers of micturitions, incontinence episodes, and urgency episodes per 24 hours, and significantly increased mean volume voided per micturition from baseline compared with solifenacin 5 mg alone.
      • Abrams P
      • Kelleher C
      • Staskin D
      • et al.
      Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony).
      • Drake MJ
      • Chapple C
      • Esen AA
      • et al.
      Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BEDSIDE).
      • Herschorn S
      • Chapple CR
      • Abrams P
      • et al.
      Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study).
      Significant differences between the combination and solifenacin monotherapy were apparent 4 weeks after treatment initiation.
      • Drake MJ
      • Chapple C
      • Esen AA
      • et al.
      Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BEDSIDE).
      Combination therapy increased the efficacy of solifenacin without increasing antimuscarinic side effects. Common side effects of mirabegron include hypertension, headache, and urinary tract infection.
      MYRBETRIQ® (Mirabegron Extended-Release Tablets) Prescribing Information.
      ,
      • Chapple CR
      • Kaplan SA
      • Mitcheson D
      • et al.
      Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder.
      A systematic review and network meta-analysis of 13 randomized, controlled trials identified significantly higher incidences of tachycardia and nasopharyngitis with mirabegron 50 mg versus placebo and of cardiac arrhythmia with mirabegron 100 mg versus placebo, and a significantly lower rate of cardiac arrhythmia versus tolterodine ER 4 mg.
      • Fest J
      • Pfalzgraf D
      • Weiss C
      • Hetjens S
      Evaluating the efficacy and tolerability of mirabegron, a β3-adrenoceptor agonist, for the treatment of overactive bladder: systematic review and network meta-analysis.
      Mirabegron prescribing information states that mirabegron may increase blood pressure and recommends periodic blood pressure measurements, but notes that in clinical trials of monotherapy or combination therapy with solifenacin 5 mg, mean increases in systolic and diastolic blood pressure from placebo were ~0.5-1 mmHg with mirabegron 50 mg.
      MYRBETRIQ® (Mirabegron Extended-Release Tablets) Prescribing Information.
      Although compliance data are limited, in a retrospective UK database study of patients who received a prescription for an OAB medication, the median time to discontinuation for mirabegron was 169 days, while that for each of the antimuscarinic agents analyzed was substantially shorter (range, 30-78 days to discontinuation).
      • Chapple CR
      • Nazir J
      • Hakimi Z
      • et al.
      Persistence and adherence with mirabegron versus antimuscarinic agents in patients with overactive bladder: a retrospective observational study in UK clinical practice.
      Two additional β3 agonists, vibegron and solabegron, are under investigation in phase 3 and phase 2 clinical trials, respectively. Vibegron monotherapy was evaluated over 12 weeks in a randomized, double-blind, placebo-controlled phase 3 trial in Japanese patients with OAB. Vibegron 50 and 100 mg once daily achieved significant improvements versus placebo for change from baseline to end of study in mean number of micturitions per day, mean number of daily episodes of urgency, urgency incontinence, and nocturia, as well as mean volume voided per micturition. These improvements were seen as early as week 4 after treatment initiation. No hypertension AEs were reported with vibegron.
      • Yoshida M
      • Takeda M
      • Gotoh M
      • et al.
      Vibegron, a novel potent and selective β3-adrenoceptor agonist, for the treatment of patients with overactive bladder: a randomized, double-blind, placebo-controlled, phase 3 study.
      Vibegron was also studied in combination with tolterodine in a phase 2b trial of patients with OAB syndrome. After 8 weeks of treatment, significant decreases in daily numbers of micturitions and urgency episodes from baseline versus placebo were obtained with monotherapy (vibegron or tolterodine), with vibegron monotherapy at 50 and 100 mg showing significant decreases as early as week 2, and after 4 weeks of treatment, significant decreases in daily numbers of micturitions from baseline versus placebo were obtained with combination therapy; both treatments were well tolerated.
      • Mitcheson HD
      • Samanta S
      • Muldowney K
      • et al.
      Vibegron (RVT-901/MK-4618/KRP-114V) administered once daily as monotherapy or concomitantly with tolterodine in patients with an overactive bladder: a multicenter, phase IIb, randomized, double-blind controlled trial.
      Unlike mirabegron, vibegron has not been shown to affect the activity of cytochrome P450 enzymes in vitro, suggesting that it has a low theoretical risk of drug–drug interactions.
      • Edmonson SD
      • Zhu C
      • Kar NF
      • et al.
      Discovery of vibegron: a potent and selective β3 adrenergic receptor agonist for the treatment of overactive bladder.
      Solabegron was studied in a randomized, double-blind, placebo-controlled trial of women with OAB-wet. Twice-daily administration of solabegron 125 mg for 8 weeks significantly reduced incontinence episodes over 24 hours from baseline to week 8 versus placebo, along with significant reductions in micturitions over 24 hours from baseline to weeks 4 and 8, and a significant increase in voided urine volume from baseline to week 8. Treatment was well tolerated.
      • Ohlstein EH
      • von Keitz A
      • Michel MC
      A multicenter, double-blind, randomized, placebo-controlled trial of the β3-adrenoceptor agonist solabegron for overactive bladder.
      Whether to initiate pharmacologic therapy with a muscarinic antagonist or a β3 agonist is not addressed by guidelines. Bothersome side effects are typically more common with antimuscarinic agents, which may influence adherence. Data from the mirabegron plus solifenacin studies suggest faster time to response with mirabegron than solifenacin,
      • Drake MJ
      • Chapple C
      • Esen AA
      • et al.
      Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BEDSIDE).
      which also could influence adherence. The longer time to discontinuation of mirabegron versus antimuscarinics may reflect better adherence.
      • Chapple CR
      • Nazir J
      • Hakimi Z
      • et al.
      Persistence and adherence with mirabegron versus antimuscarinic agents in patients with overactive bladder: a retrospective observational study in UK clinical practice.
      Alternatively, both types of drugs may be initiated in combination. Because antimuscarinic agents and β3-receptor agonists have different mechanisms of action, combination therapy with a drug from each of these classes may be considered.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      Combining Behavioral and Pharmacologic Therapy

      Given the high discontinuation rates of behavioral and pharmacologic therapy, starting treatment with a combination of both may help address poor adherence. This may achieve better overall efficacy than either method alone for appropriate patients. However, while AUA/SUFU and NICE guidelines do not advise how to implement a behavioral-pharmacologic therapy protocol,

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,

      National Institute for Health and Care Excellence. Urinary incontinence and pelvic organ prolapse in women: management. NG123. 2019. Available at:https://www.nice.org.uk/guidance/ng123. Accessed July 23, 2019.

      AUA/SUFU notes that a patient does not have to complete one line of therapy to proceed to the next.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      A discussion of patient goals for treatment after initial diagnosis may aid in identifying patients appropriate for behavioral-pharmacologic therapy. The appropriate duration of initial therapy also must be determined, and may vary among patients. Data suggest that β3 agonist therapy provides benefits faster than antimuscarinic agents,
      • Drake MJ
      • Chapple C
      • Esen AA
      • et al.
      Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BEDSIDE).
      which may support a combination of a β3 agonist and behavioral therapy, given the potential for increased patient satisfaction and better adherence rates. Patients will often present after many years of suffering. Rather than just selecting monotherapy with behavioral modifications that might take several weeks to achieve a partial response, clinicians initially may consider instituting oral agents along with behavioral changes. Starting oral therapy simultaneously is often driven by the patient's prior experience with OAB (both duration of symptoms and severity) and the expectation of the speed with which they will start to see relief from treatment.

      Benign Prostatic Hyperplasia and OAB

      Men with benign prostatic hyperplasia may have OAB in the form of concomitant lower urinary tract bladder storage symptoms, such as frequent micturition and nocturia.
      • Kaplan SA
      • Roehrborn CG
      • Gong J
      • Sun F
      • Guan Z
      Add-on fesoterodine for residual storage symptoms suggestive of overactive bladder in men receiving α-blocker treatment for lower urinary tract symptoms.
      ,
      • Rosen R
      • Altwein J
      • Boyle P
      • et al.
      Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7).
      Results from studies of antimuscarinics (eg, tolterodine ER)
      • Gacci M
      • Novara G
      • De Nunzio C
      • et al.
      Tolterodine extended release in the treatment of male OAB/storage LUTS: a systematic review.
      and a β3-adrenergic agonist (ie, mirabegron)
      • Su S
      • Lin J
      • Liang L
      • Liu L
      • Chen Z
      • Gao Y
      The efficacy and safety of mirabegron on overactive bladder induced by benign prostatic hyperplasia in men receiving tamsulosin therapy: a systematic review and meta-analysis.
      alone or in combination with standard therapy for benign prostatic hyperplasia have shown improvement in these symptoms.

      Third-Line Therapies

      OAB patients who are refractory to first- and second-line treatments and are not candidates for behavioral therapy may be offered third-line therapy with intradetrusor onabotulinumtoxinA injections, PTNS, or SNS.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      OnabotulinumtoxinA injections require follow-up, which may involve repeat injections and, in some cases, the need for catheterization. The AUA/SUFU guidelines

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      consider intradetrusor onabotulinumtoxinA a standard to offer patients that have been carefully selected and thoroughly counseled and have been refractory to first- and second-line therapies. Patients report high satisfaction, and in one study, 81% of those continuing treatment stated that they would consider life-long treatment. Among the 23/100 patients who discontinued treatment, reasons were lack of efficacy, need for intermittent self-catheterization or development of a urinary tract infection, and symptom improvement requiring no further treatment.
      • Malde S
      • Dowson C
      • Fraser O
      • et al.
      Patient experience and satisfaction with Onabotulinumtoxin A for refractory overactive bladder.
      The guidelines recommend PTNS may be offered in carefully selected patients.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      PTNS has efficacy similar to antimuscarinic therapy, with a more tolerable AE profile.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      PTNS has been shown to reduce baseline incontinence, frequency of micturition, and nocturia episodes.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      However, PTNS is an invasive procedure that may involve 3 months of weekly visits for 30-minute stimulation sessions with monthly follow-up visits.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      The guidelines recommend SNS may be offered in carefully selected patients with severe refractory OAB symptoms, or in patients who are not candidates for second-line therapy.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      SNS has shown success in reducing OAB symptoms in approximately 70% of patients with stage I implants who were refractive to standard medication.
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.
      SNS carries a risk of the need for additional surgeries.

      Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. Available at:https://www.auanet.org/guidelines/overactive-bladder-(oab)-guideline. Accessed July 23, 2019.

      ,
      • Corcos J
      • Przydacz M
      • Campeau L
      • et al.
      CUA guideline on adult overactive bladder.

      CONCLUSION

      Guideline-directed therapy has demonstrated efficacy in alleviating the symptoms of OAB syndrome, but poor adherence highlights the need for improved clinician/patient interaction, consisting of patient education, involvement in treatment planning, and regular follow-up. Each of the recommended pharmacologic therapies has advantages and limitations, raising the question of the characteristics of an ideal drug. In a survey of women with OAB symptoms, those who had used OAB medications but were not currently being treated listed desirable characteristics as no associated nausea, dry eyes, or constipation, and not having to take a high dose of medication.
      • Dmochowski RR
      • Newman DK
      Impact of overactive bladder on women in the United States: results of a national survey.
      Other features may include rapid onset of effect, few drug–drug interactions, no contraindications, good adherence, and tolerable/manageable side effects.
      A combination of behavioral and pharmacologic therapies may represent the best chance for success, provided an ongoing dialogue exists between clinicians and patients. The process should start with patient assessment and goal setting to identify a clear plan, after which initial treatment with a trial of a combination of behavioral therapy and β3-adrenergic agonist therapy may be pursued. When the patient returns for follow-up, additional therapy may be considered if needed, and any further testing may be carried out. Overall, tailoring initiation and treatment modalities for OAB management with behavioral and pharmacologic therapy in appropriate patients may provide patients with the greatest opportunity to receive the long-term treatment effect they need.

      Acknowledgment

      The authors would like to thank Alan J. Wein, MD, PhD, for his insightful comments during preparation of this manuscript. In accordance with Good Publication Practice guidelines, Stephanie Leinbach, PhD, and The Curry Rockefeller Group, LLC, Tarrytown, NY, provided medical writing and editorial support for this article—including formatting, proofreading, copy editing, and fact checking—at the request of the authors. This support was funded by Urovant Sciences. The authors had sole control of the content and the decision to submit this manuscript.

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