AUA: Overactive Bladder (2019)

See Original Guidelines

See Pharmacological Management of LUTS Chapter Notes

• This guideline does not apply to patients with symptoms related to neurologic conditions

Definitions

• Urgency: complaint of a sudden, compelling desire to pass urine which is difficult to defer
• Urgency urinary incontinence: involuntary leakage of urine associated with a sudden compelling desire to void
• Overactive bladder: Urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a urinary tract infection (UTI) or other obvious pathology.
  • OAB symptoms consist of 4 components:
    • Urgency
    • Frequency
    • Nocturia
      • OAB symptoms (frequency, urgency and urgency incontinence) may occur only at night, causing a single symptom of nocturia.
    • Urgency incontinence
• Nocturia: interruption of sleep one or more times because of the need to void

Epidemiology

• Prevalence
  • Females: 9-43%
  • Males: 7-27%
• OAB symptom prevalence and severity tend to increase with age.
• UUI is consistently more common in females than in males

Natural history

• A proportion of OAB cases (37-39%) remit during a given year, but the majority of patients have symptoms for years.
• OAB constitutes a significant burden for patients.
  • Carrying out the activities of daily life and engaging in social and occupational activities can be profoundly affected by lack of bladder control and incontinence.
  • Urinary incontinence in particular may have severe psychological and social consequences, resulting in restricted activities and unwillingness to be exposed to environments where access to a bathroom may be difficult.
  • Patients also report negative impact on sexual function and marital satisfaction
• It is common for patients to have suffered with their symptoms for an extended time before seeking medical advice.

Diagnosis and Evaluation

• Clinical diagnosis
  • When urinary frequency (both daytime and night) and urgency, with or without urgency incontinence, in the absence of UTI or other obvious pathology are self-reported as bothersome, the patient may be diagnosed with OAB

Recommended Investigations

Mandatory (2)

1. History and Physical Exam
2. Urinalysis

Optional (4)

1. Urine culture
2. Post void residual
3. Bladder diaries
4. Symptom questionnaire

Not recommended in the initial workup of the uncomplicated patient

1. Urodynamics
2. Cystoscopy
3. Diagnostic renal and bladder ultrasound
4. For complicated or refractory patients, the choice of additional diagnostic tests depends on patient history, QoL and clinician judgment. Neurogenic OAB requires specific evaluation.

History

• Characterize lower urinary tract symptoms (storage and voiding/emptying), including duration of symptoms and baseline symptoms
  • Assess bladder storage symptoms associated with OAB (e.g., urgency, urgency incontinence, frequency, nocturia) and other bladder storage problems (e.g., stress incontinence episodes)
    • Urinary frequency
      • Varies across individuals.
        • In community-dwelling healthy adults, normal frequency consists of voiding every 3-4 hours with a median of approximately 6 voids a day.
        • Traditionally, up to 7 micturition episodes during waking hours has been considered normal, but this number is highly variable based upon hours of sleep, fluid intake, comorbid medical conditions and other factors.
      • Can be reliably measured with a voiding diary.
    • Incontinence
      • Can be measured reliably with a diary and the quantity of urine leakage can be measured with pad tests.
  • Assess bladder emptying (e.g., hesitancy, straining to void, prior history of urinary retention, force of stream, intermittency of stream).
• Amount and type of fluid intake (e.g., with or without caffeine).
  • Excessive fluid intake can produce voiding patterns that mimic OAB symptoms.
  • Patients who do not appear able to provide accurate intake and voiding information should fill out a fluid diary.
• Current medications
  • Should be reviewed to ensure that symptoms are not related to medications.
• Co-morbid conditions such as neurologic diseases and other genitourinary conditions should be considered as they directly impact bladder function.
  • Patients with co-morbid conditions and OAB symptoms would be considered complicated OAB patients. These co-morbid conditions include neurologic diseases (i.e., stroke, multiple sclerosis, spinal cord injury), mobility deficits, medically complicated/uncontrolled diabetes, fecal motility disorders (fecal incontinence/constipation), chronic pelvic pain, history of recurrent urinary tract infections (UTIs), gross hematuria, prior pelvic/vaginal surgeries (incontinence/prolapse surgeries), pelvic cancer (bladder, colon, cervix, uterus, prostate) and pelvic radiation. The female patient with significant prolapse (i.e., prolapse beyond the introitus) also may be considered a complicated OAB patient. A patient who has failed multiple anti-muscarinics to control OAB symptoms could also be considered a complicated OAB patient.
• Degree of bother
  • If patient is not significantly bothered by his/her bladder symptoms, then there is a less compelling reason to treat the symptoms.

Physical exam

1. Abdominal exam should be performed to assess for scars, masses, hernias and areas of tenderness as well as for suprapubic distension that may indicate urinary retention
2. Rectal/genitourinary exam to rule out pelvic floor disorders (e.g., pelvic floor muscle spasticity, pain, pelvic organ prolapse) in females and prostatic pathology in males should be performed. In menopausal females, atrophic vaginitis should be assessed as a possible contributing factor to incontinence symptoms. Assess for perineal skin for rash or breakdown. The examiner also should assess perineal sensation, rectal sphincter tone and ability to contract the anal sphincter in order to evaluate pelvic floor tone and potential ability to perform pelvic floor exercises (e.g., the ability to contract the levator ani muscles) as well as to rule out impaction and constipation.
3. Assessment of lower extremities for edema should be done to give the clinician an assessment of the potential for fluid shifts during periods of postural changes
4. Patient’s attire and ability to dress independently
   • The ability of the patient to dress independently is informative of sufficient motor skills related to toileting habits. This can provide information on the cognitive function of the patient, which is important to evaluate when considering anticholinergics.
   • A Mini-Mental State Examination (MMSE)should be conducted on all patients who may be at risk for cognitive impairment to determine whether symptoms are aggravated by cognitive problems, to ensure that they will be able to follow directions for behavioral therapy and/or to determine the degree of risk for cognitive decline with anti-muscarinic therapy.

Urinalysis

• Rule out UTI and hematuria

Urine culture

• Not necessary unless indication of infection (i.e., nitrites/leukocyte esterase on dipstick, pyuria/bacteriuria on microscopic exam) is found
  • May be appropriate in certain patients given that a urinalysis may be unreliable.
• If evidence of infection is detected, then a culture should be performed, the infection treated appropriately and the patient should be queried regarding symptoms once the infection has cleared.

Post-void Residual

• Measurement of the PVR is not necessary for patients who are receiving first-line behavioral interventions or for uncomplicated patients receiving antimuscarinic medications.
  • Anti-muscarinics should be used with caution in patients with PVR 250–300 mL.
• Indications to assess PVR (4)
  1. Presence of voiding/obstructive symptoms
  2. History of incontinence surgery or prostatic surgery
  3. Neurologic diagnoses
  4. Clinician discretion

Bladder diaries

• Diaries that document intake and voiding behavior
• May be useful, particularly for patient education and to document baseline symptoms and treatment efficacy              

Symptoms questionnaire

• Validated symptom questionnaires are useful in the quantification of bladder symptoms and bother- changes with OAB treatment.

Differential Diagnosis

1. Nocturia
2. Polydipsia and polyuria
3. Interstitial cystitis/bladder pain syndrome
4. Atrophic vaginitis

Nocturia

• Often due to factors unrelated to OAB, including excessive nighttime urine production and sleep apnea.
• The differential of nocturia includes nocturnal polyuria, low nocturnal bladder capacity or both.
  • In nocturnal polyuria, the production of greater than 20 to 33% of total 24 hour urine output during the period of sleep, which is age-dependent with 20% for younger individuals and 33% for elderly individuals. Nocturnal voids are frequently normal or large volume as opposed to the small volume voids commonly observed in nocturia associated with OAB.
  • Sleep disturbances, vascular and/or cardiac disease and other medical conditions are often associated with nocturnal polyuria.

Polydipsia and polyuria

• In OAB, urinary frequency is associated with many small volume voids. Frequency that is the result of polydipsia and resulting polyuria may mimic OAB; the two can only be distinguished with the use of frequency-volume charts. In polydipsia, urinary frequency occurs with normal or large volume voids and the intake is volume matched. In this case, the frequency is appropriate because of the intake volume and the patient does not have OAB
• Polydipsia-related frequency is physiologically self-induced and should be managed with education and consideration of fluid management.
• Diabetes insipidus also is associated with frequent, large volume voids and should be distinguished from OAB.

Interstitial cystitis/bladder pain syndrome

• Clinical presentation of interstitial cystitis/bladder pain syndrome shares the OAB symptoms of urinary frequency and urgency, with or without urgency incontinence
• Bladder and/or pelvic pain, including dyspareunia, is a crucial component of its presentation in contradistinction to OAB.

Atrophic vaginitis

• In the menopausal female patient, atrophic vaginitis can be a contributing factor to incontinence symptoms.
• There is some evidence for symptom improvement with the use of vaginal (but not systemic) estrogen.

Management

• OAB may compromise QoL but generally does not affect survival. A treatment plan, therefore, should carefully weigh the patient’s potential benefit of a particular treatment against that treatment’s risk for, severity and reversibility of AEs.
• Provide education to patients regarding normal lower urinary tract function, what is known about OAB, the benefits vs. risks/burdens of the available treatment alternatives and the fact that acceptable symptom control may require trials of multiple therapeutic options before it is achieved.
  • Counsel patients that OAB has a variable and chronic course likely requiring multiple management strategies over time with no single ideal treatment and understands that treatments vary in invasiveness, risk of AEs and reversibility.
  • Most OAB treatments improve patient symptoms but are unlikely to eliminate all symptoms
  • Treatment failure occurs when the patient with reasonable expectations does not have the anticipated symptom improvement or is unable to tolerate the treatment due to AEs; lack of efficacy and the presence of intolerable AEs reduce compliance

Options

1. Observation
2. Behavioral therapies
3. Medications
4. Other

Observation

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

Behavioral Therapies (first-line)

• A group of risk-free tailorable therapies, which improve individual symptoms by changing patient behavior or the patient’s environment.
• Includes (3):
  1. Bladder control strategies, such as with bladder training and delayed voiding, to modify bladder symptoms by changing voiding habits
  2. Pelvic floor muscle training to improve control and techniques for urge suppression.
  3. Fluid management
     1. 25% reduction in fluid intake reduces frequency and urgency
• First-line treatments because they are as effective in reducing symptom levels as are antimuscarinic medications.
  • Randomized trials indicates that behavioral treatments are generally either equivalent to or superior to medications in terms of reducing incontinence episodes, improving frequency and nocturia and improving QoL.
  • While most patients do not experience complete symptom relief, most patients experience significant reductions in symptoms and improvements in QoL.
• May be combined with pharmacologic management.
• Weight loss may improve incontinence specifically

Pharmacologic management (second-line)

Options

• Recommended
  • Oral anti-cholinergic
  • Oral β3-adrenoceptor agonists
• May be offered
  • Transdermal oxybutynin (patch or gel)

Anti-cholinergics

• Options
  1. Oral
     1. Darifenacin
     2. Fesoterodine
     3. Oxybutynin
     4. Solifenacin
     5. Tolterodine
     6. Trospium
  2. Transdermal oxybutynin (patch or gel)

• Efficacy
  • No compelling evidence for differential efficacy across oral medications
    • Since similar efficacy observed for all oral anti-cholinergic medications, the choice of medication is patient dependent; however, AE profiles for dry mouth and constipation vary with medications
  • Patients with more severe symptoms, on average, experience greater symptom reductions.
    • Only patients with relatively low baseline symptom levels are likely to experience complete symptom relief
• Contraindications
  • Narrow angle glaucoma (unless approved by the treating ophthalmologist)
  • Impaired gastric emptying or a history of urinary retention
    • Prior to initiation of anti-cholinergics, a patient at risk for gastric emptying problems or for urinary retention should receive clearance from a gastroenterologist or urologist, respectively.
      • A PVR may be useful in any patient suspected of a higher risk of urinary retention.
  • Use of solid oral forms of potassium chloride
    • Reduced gastric emptying potentially caused by the anti-cholinergics may increase the potassium absorption of these agents.
    • Anti-cholinergic therapy may be used with caution with alternative forms of potassium chloride.
  • Dementia
    • Anti-cholinergics may be contraindicated entirely depending on the level of cognitive impairment.
  • Use caution in prescribing anti-cholinergics or β3-adrenoceptor agonists in the frail OAB patient.
    • OAB medication trials generally are not conducted in the frail elderly, resulting in a lack of efficacy and AE data in this group.
      • Additional AEs are reported in this group, including impaired thermoregulation with dangerous core temperature elevation.
    • Polypharmacy is common in frail community-dwelling patients, placing them at higher risk for AEs, including impaired cognition.
• Adverse events
  • Cognitive impairment
    • Patients may not recognize that memory deterioration has occurred, making it essential for the clinician, family members and caregivers to monitor for these effects
    • While newer agents (eg, darifenacin) are reported to be less likely to produce cognitive deficits in elderly patients, the literature is limited; the two-week drug administration period in these studies is not long enough to yield definitive conclusions.
  • Constipation
    • Can be mitigated with adequate dietary fiber and fluid, psyllium-based fiber supplements, regular exercise and normal bowel habits.
  • Dry mouth
    • Can be mitigated with oral lubricants, small sips of water, sucking on sugar-free hard candies and chewing sugar-free gum, and avoiding mouthwashes with alcohol.
    • If an immediate release (IR) and an extended release (ER) formulation are available, then ER formulations should preferentially be prescribed over IR formulations because of lower rates of dry mouth.
      • ER formulations of oxybutynin and tolterodine result in significantly fewer patient reports of dry mouth than the IR formulations of either medication.
  • Constipation and dry mouth should be managed before abandoning effective anti-cholinergic therapy.
    • Management may include bowel management, fluid management, dose modification or alternative anti-cholinergics.
  • Use caution in prescribing anti-cholinergics in patients who are already using other medications with anti-cholinergic properties.
    • Medications with anti-cholinergic properties include (3)
      1. Tricyclic antidepressants
      2. Acetylcholinesterase inhibitors
      3. Medications for Parkinsonism, other extra-pyramidal diseases and Alzheimer’s disease.
    • Certain anti-nausea medications and those with atropine-like properties may also potentiate AEs.
  • Begin with the lowest possible dose and titrate slowly while carefully assessing for the balance between symptom control and AEs.
    • In older patients who may metabolize drugs differently, it is advisable to start with a minimal dose and titrate as tolerated.
  • Optimizing medication tolerability is critical to obtaining patient compliance in the treatment of this chronic condition.
    • Compliance with a once daily dosing is greater than with medications taken more than once a day.
• Failure of medical therapy
  • Patients who are refractory to behavioral and medical therapy should be evaluated by an appropriate specialist if they desire additional
  • If a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one anti-muscarinic medication, then a dose modification or a different anti-muscarinic medication or a β3-adrenoceptor agonist may be tried.
  • Clinicians may consider combination therapy with an anti-muscarinic and β3-adrenoceptor agonist for patients refractory to monotherapy with either anti-muscarinics or β3-adrenoceptor agonists.

PTNS and Neuromodulation (third-line)

• Before a patient is exposed to third-line therapies with increased risk compared to behavioral or medical therapy, the patient’s realistic desire for further treatment should be ascertained, and a comprehensive evaluation should be conducted to confirm the diagnosis of OAB and not another disease process

• Neuromodulation or onabotulinumtoxinA therapy may be offered to the carefully selected patient who has failed behavioral and anti-muscarinic therapy or who is not a candidate for these therapies and continues to have bothersome symptoms after appropriate counseling.
• Practitioners and patients should persist with new treatments for an adequate trial in order to determine whether the therapy is efficacious and tolerable. Combination therapeutic approaches should be assembled methodically, with the addition of new therapies occurring only when the relative efficacy of the preceding therapy is known. Therapies that do not demonstrate efficacy after an adequate trial should be ceased.

Peripheral tibial nerve stimulation (PTNS)

• may offer peripheral tibial nerve stimulation (PTNS) as third-line treatment in a carefully selected patient population.
• FDA-approved for OAB treatment

Neuromodulation

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

OnabotulinumtoxinA

• may offer intradetrusor onabotulinumtoxinA (100U) as third-line treatment in the carefully-selected and thoroughly-counseled patient who has been refractory to first- and second-line OAB treatments. The patient must be able and willing to return for frequent post-void residual evaluation and able and willing to perform self-catheterization if necessary.
• Not FDA-approved in non-neurogenic OAB patients

Augmentation cystoplasty and urinary diversion (fourth-line)

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

Additional treatments

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

Follow-Up

• Should offer follow up with the patient to assess compliance, efficacy, side effects and possible alternative treatments.